Kerri Wachter

PORTO, PORTUGAL – MRI used in combination with neurologic/neuropsychometric evaluations enables physicians to distinguish among three subtypes of mild cognitive impairment, thus potentially permitting early and effective subtype-specific prophylaxis or therapy before conversion of a given subtype to its corresponding dementia, according to data presented at the at the Fourth International Congress on Vascular Dementia.

The study involved 166 volunteers recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia, said Dr. John S. Meyer, a professor of neurology at Baylor College of Medicine in Houston. All of the volunteers were followed for at least 6 years and underwent serial evaluations every 3–6 months involving medical, neurologic, and psychometric assessments (Mini-Mental State plus Cognitive Capacity Screening Examination as Combined Mini-Mental Cognitive Capacity Screening Examinations and Hamilton Depression Scales).

Normal cognition was defined as a Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC) score greater than 42 (52 participants). Based on positive findings on accepted clinical assessment (plus CMC scores less than 42), 30 participants were determined to have neurodegenerative MCI, 35 had vascular MCI, and 8 had Parkinson's-Lewy body MCI.

Neurodegenerative MCI, vascular MCI, and Parkinson's disease MCI were considered to be prodromal for AD, vascular dementia (VaD), and Parkinson's disease dementia (PDD), respectively, said Dr. Meyer, director of the Cerebral Blood Flow Laboratory at the Michael E. Debakey Veterans Affairs Medical Center in Houston.

Later, 19 of the 30 participants with neurodegenerative MCI converted to AD, 17 of the 35 with vascular MCI progressed to VaD, and 5 of 8 with Parkinson's-Lewy body MCI converted to PDD. Those with AD met National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria; those with VaD met National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria; those with PDD met DSM-IV criteria.

MRI scans were performed annually. A visual rating scale was used to perform MRI analysis. Volumetric measurements were made of the temporal horn and entorhinal cortex by enlarging regions of interest.

Subjects with MCI and dementia tended to be older than cognitively normal subjects. Those with vascular MCI had more depressive symptoms than normal subjects. Histories of hypertension, heart disease, diabetes, transient ischemic attacks, and stroke were more common in subjects with vascular MCI than in the normal group. A family history of neurodegenerative disease was more common among subjects with neurodegenerative MCI and AD than in normal subjects. A history of transient ischemic attacks and stroke were more common among subjects with Parkinson's MCI than among normal subjects.

On MRI, cortical atrophy was more frequently seen in MCI and dementia groups compared with the cognitively normal group–except for the parietal and occiptal cortices in the Parkinson's MCI group and the occipital cortex in the PDD group. Subjects with AD displayed significantly more temporal cortical atrophy than those with neurodegenerative MCI.

Based on volumetric measurements, subjects in MCI and dementia groups had more significant frontal horn and third ventricle enlargement, compared with those in the normal group. Subjects with neurodegenerative MCI, AD, and PDD showed significantly more temporal horn enlargement.

Subjects with vascular MCI had less significant frontal horn enlargement than VaD subjects. Those with neurodegenerative MCI displayed more significant temporal horn enlargement than did those with vascular MCI. Among subjects with MCI and dementia subtypes–except those with vascular MCI–hippocampal and entorhinal cortex atrophy was greater than in normal subjects.

Vascular groups showed more white matter infarcts, leukoaraiosis, and lacunar infarcts than the normal, neurodegenerative, or Parkinson's groups.

In particular, vascular MCI subjects showed more white matter lacunar infarcts and leukoaraiosis than those with neurodegenerative or Parkinson's MCI. Subjects with neurodegenerative MCI showed more medial/temporal lobe atrophy than other types of MCI. Parkinson's MCI subjects had significantly greater enlargement of the third ventricle than neurodegenerative and vascular MCI subjects.

PORTO, PORTUGAL – MRI used in combination with neurologic/neuropsychometric evaluations enables physicians to distinguish among three subtypes of mild cognitive impairment, thus potentially permitting early and effective subtype-specific prophylaxis or therapy before conversion of a given subtype to its corresponding dementia, according to data presented at the at the Fourth International Congress on Vascular Dementia.

The study involved 166 volunteers recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia, said Dr. John S. Meyer, a professor of neurology at Baylor College of Medicine in Houston. All of the volunteers were followed for at least 6 years and underwent serial evaluations every 3–6 months involving medical, neurologic, and psychometric assessments (Mini-Mental State plus Cognitive Capacity Screening Examination as Combined Mini-Mental Cognitive Capacity Screening Examinations and Hamilton Depression Scales).

Normal cognition was defined as a Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC) score greater than 42 (52 participants). Based on positive findings on accepted clinical assessment (plus CMC scores less than 42), 30 participants were determined to have neurodegenerative MCI, 35 had vascular MCI, and 8 had Parkinson's-Lewy body MCI.

Neurodegenerative MCI, vascular MCI, and Parkinson's disease MCI were considered to be prodromal for AD, vascular dementia (VaD), and Parkinson's disease dementia (PDD), respectively, said Dr. Meyer, director of the Cerebral Blood Flow Laboratory at the Michael E. Debakey Veterans Affairs Medical Center in Houston.

Later, 19 of the 30 participants with neurodegenerative MCI converted to AD, 17 of the 35 with vascular MCI progressed to VaD, and 5 of 8 with Parkinson's-Lewy body MCI converted to PDD. Those with AD met National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria; those with VaD met National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria; those with PDD met DSM-IV criteria.

MRI scans were performed annually. A visual rating scale was used to perform MRI analysis. Volumetric measurements were made of the temporal horn and entorhinal cortex by enlarging regions of interest.

Subjects with MCI and dementia tended to be older than cognitively normal subjects. Those with vascular MCI had more depressive symptoms than normal subjects. Histories of hypertension, heart disease, diabetes, transient ischemic attacks, and stroke were more common in subjects with vascular MCI than in the normal group. A family history of neurodegenerative disease was more common among subjects with neurodegenerative MCI and AD than in normal subjects. A history of transient ischemic attacks and stroke were more common among subjects with Parkinson's MCI than among normal subjects.

On MRI, cortical atrophy was more frequently seen in MCI and dementia groups compared with the cognitively normal group–except for the parietal and occiptal cortices in the Parkinson's MCI group and the occipital cortex in the PDD group. Subjects with AD displayed significantly more temporal cortical atrophy than those with neurodegenerative MCI.

Based on volumetric measurements, subjects in MCI and dementia groups had more significant frontal horn and third ventricle enlargement, compared with those in the normal group. Subjects with neurodegenerative MCI, AD, and PDD showed significantly more temporal horn enlargement.

Subjects with vascular MCI had less significant frontal horn enlargement than VaD subjects. Those with neurodegenerative MCI displayed more significant temporal horn enlargement than did those with vascular MCI. Among subjects with MCI and dementia subtypes–except those with vascular MCI–hippocampal and entorhinal cortex atrophy was greater than in normal subjects.

Vascular groups showed more white matter infarcts, leukoaraiosis, and lacunar infarcts than the normal, neurodegenerative, or Parkinson's groups.

In particular, vascular MCI subjects showed more white matter lacunar infarcts and leukoaraiosis than those with neurodegenerative or Parkinson's MCI. Subjects with neurodegenerative MCI showed more medial/temporal lobe atrophy than other types of MCI. Parkinson's MCI subjects had significantly greater enlargement of the third ventricle than neurodegenerative and vascular MCI subjects.

PORTO, PORTUGAL – MRI used in combination with neurologic/neuropsychometric evaluations enables physicians to distinguish among three subtypes of mild cognitive impairment, thus potentially permitting early and effective subtype-specific prophylaxis or therapy before conversion of a given subtype to its corresponding dementia, according to data presented at the at the Fourth International Congress on Vascular Dementia.

The study involved 166 volunteers recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia, said Dr. John S. Meyer, a professor of neurology at Baylor College of Medicine in Houston. All of the volunteers were followed for at least 6 years and underwent serial evaluations every 3–6 months involving medical, neurologic, and psychometric assessments (Mini-Mental State plus Cognitive Capacity Screening Examination as Combined Mini-Mental Cognitive Capacity Screening Examinations and Hamilton Depression Scales).

Normal cognition was defined as a Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC) score greater than 42 (52 participants). Based on positive findings on accepted clinical assessment (plus CMC scores less than 42), 30 participants were determined to have neurodegenerative MCI, 35 had vascular MCI, and 8 had Parkinson's-Lewy body MCI.

Neurodegenerative MCI, vascular MCI, and Parkinson's disease MCI were considered to be prodromal for AD, vascular dementia (VaD), and Parkinson's disease dementia (PDD), respectively, said Dr. Meyer, director of the Cerebral Blood Flow Laboratory at the Michael E. Debakey Veterans Affairs Medical Center in Houston.

Later, 19 of the 30 participants with neurodegenerative MCI converted to AD, 17 of the 35 with vascular MCI progressed to VaD, and 5 of 8 with Parkinson's-Lewy body MCI converted to PDD. Those with AD met National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria; those with VaD met National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria; those with PDD met DSM-IV criteria.

MRI scans were performed annually. A visual rating scale was used to perform MRI analysis. Volumetric measurements were made of the temporal horn and entorhinal cortex by enlarging regions of interest.

Subjects with MCI and dementia tended to be older than cognitively normal subjects. Those with vascular MCI had more depressive symptoms than normal subjects. Histories of hypertension, heart disease, diabetes, transient ischemic attacks, and stroke were more common in subjects with vascular MCI than in the normal group. A family history of neurodegenerative disease was more common among subjects with neurodegenerative MCI and AD than in normal subjects. A history of transient ischemic attacks and stroke were more common among subjects with Parkinson's MCI than among normal subjects.

On MRI, cortical atrophy was more frequently seen in MCI and dementia groups compared with the cognitively normal group–except for the parietal and occiptal cortices in the Parkinson's MCI group and the occipital cortex in the PDD group. Subjects with AD displayed significantly more temporal cortical atrophy than those with neurodegenerative MCI.

Based on volumetric measurements, subjects in MCI and dementia groups had more significant frontal horn and third ventricle enlargement, compared with those in the normal group. Subjects with neurodegenerative MCI, AD, and PDD showed significantly more temporal horn enlargement.

Subjects with vascular MCI had less significant frontal horn enlargement than VaD subjects. Those with neurodegenerative MCI displayed more significant temporal horn enlargement than did those with vascular MCI. Among subjects with MCI and dementia subtypes–except those with vascular MCI–hippocampal and entorhinal cortex atrophy was greater than in normal subjects.

Vascular groups showed more white matter infarcts, leukoaraiosis, and lacunar infarcts than the normal, neurodegenerative, or Parkinson's groups.

In particular, vascular MCI subjects showed more white matter lacunar infarcts and leukoaraiosis than those with neurodegenerative or Parkinson's MCI. Subjects with neurodegenerative MCI showed more medial/temporal lobe atrophy than other types of MCI. Parkinson's MCI subjects had significantly greater enlargement of the third ventricle than neurodegenerative and vascular MCI subjects.

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Dr. Akihiko Nunomura of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were done on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

The researchers are now focusing on better understanding the mechanism behind the amyloid-β/8-hydroxyguanosine relationship, said Dr. Perry.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year-old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Dr. Akihiko Nunomura of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were done on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

The researchers are now focusing on better understanding the mechanism behind the amyloid-β/8-hydroxyguanosine relationship, said Dr. Perry.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year-old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Dr. Akihiko Nunomura of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were done on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

The researchers are now focusing on better understanding the mechanism behind the amyloid-β/8-hydroxyguanosine relationship, said Dr. Perry.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year-old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Gonadal steroid deprivation has been reported to increase skeletal sensitivity to the bone-resorbing properties of parathyroid hormone (PTH) in men. It's not clear whether this effect is due to the absence of estrogens, androgens, or both, said Dr. Benjamin Z. Leder, of Massachusetts General Hospital in Boston.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. These men were testosterone and estradiol deficient for the duration of the study. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. These men were testosterone sufficient and estradiol deficient. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. These men were testosterone deficient but estradiol sufficient. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All men underwent infusions of PTH (1–34) at baseline and at 6 weeks. Serum levels of the bone turnover marker cross-linked N-telopeptides (NTx) of type I collagen were measured during the infusions.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx increased during PTH infusion in all groups at all time points.

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Gonadal steroid deprivation has been reported to increase skeletal sensitivity to the bone-resorbing properties of parathyroid hormone (PTH) in men. It's not clear whether this effect is due to the absence of estrogens, androgens, or both, said Dr. Benjamin Z. Leder, of Massachusetts General Hospital in Boston.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. These men were testosterone and estradiol deficient for the duration of the study. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. These men were testosterone sufficient and estradiol deficient. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. These men were testosterone deficient but estradiol sufficient. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All men underwent infusions of PTH (1–34) at baseline and at 6 weeks. Serum levels of the bone turnover marker cross-linked N-telopeptides (NTx) of type I collagen were measured during the infusions.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx increased during PTH infusion in all groups at all time points.

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Gonadal steroid deprivation has been reported to increase skeletal sensitivity to the bone-resorbing properties of parathyroid hormone (PTH) in men. It's not clear whether this effect is due to the absence of estrogens, androgens, or both, said Dr. Benjamin Z. Leder, of Massachusetts General Hospital in Boston.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. These men were testosterone and estradiol deficient for the duration of the study. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. These men were testosterone sufficient and estradiol deficient. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. These men were testosterone deficient but estradiol sufficient. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All men underwent infusions of PTH (1–34) at baseline and at 6 weeks. Serum levels of the bone turnover marker cross-linked N-telopeptides (NTx) of type I collagen were measured during the infusions.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx increased during PTH infusion in all groups at all time points.

NASHVILLE, TENN. — Women with postmenopausal osteoporosis are no more likely to adhere to bisphosphonate therapy with weekly dosing than with daily dosing, according to data presented in a poster at the annual meeting of the American Society for Bone and Mineral Research.

In a retrospective study of 12,538 women with postmenopausal osteoporosis, risk of adherence failure did not differ between patients receiving weekly versus daily bisphosphonate therapy, according to Derek Weycker, Ph.D., of Policy Analysis Inc. in Brookline, Mass., and colleagues.

The researchers reviewed integrated medical and outpatient pharmacy claims from 1998 to 2003 for women aged 45 years and older with postmenopausal osteoporosis from 30 U.S. health plans.

Women were said to have postmenopausal osteoporosis if they had one or more medical claims with a corresponding diagnosis code. They also had no evidence of secondary causes of osteoporosis.

Adherence was assessed daily from the date of therapy initiation through the date of a switch to another antiosteoporosis drug or formulation, date they left the plan, or Dec. 31, 2003—whichever came first.

Within 6 months of initiating therapy, 57% of the 9,117 women on weekly therapy and 62% of the 3,421 women on daily therapy were considered to have adherence failure. At 1 year, 66% of those on weekly therapy and 71% of those on daily therapy had adherence failure. At 2.5 years, the rates were 80% for weekly therapy and 82% for daily therapy.

Risk of failure was higher among women aged 65 years and older but lower in those with a fracture history. The researchers did not assess adherence for specific drugs.

The research was funded by Amgen Inc., which is currently investigating a fully monoclonal antibody for osteoporosis.

NASHVILLE, TENN. — Women with postmenopausal osteoporosis are no more likely to adhere to bisphosphonate therapy with weekly dosing than with daily dosing, according to data presented in a poster at the annual meeting of the American Society for Bone and Mineral Research.

In a retrospective study of 12,538 women with postmenopausal osteoporosis, risk of adherence failure did not differ between patients receiving weekly versus daily bisphosphonate therapy, according to Derek Weycker, Ph.D., of Policy Analysis Inc. in Brookline, Mass., and colleagues.

The researchers reviewed integrated medical and outpatient pharmacy claims from 1998 to 2003 for women aged 45 years and older with postmenopausal osteoporosis from 30 U.S. health plans.

Women were said to have postmenopausal osteoporosis if they had one or more medical claims with a corresponding diagnosis code. They also had no evidence of secondary causes of osteoporosis.

Adherence was assessed daily from the date of therapy initiation through the date of a switch to another antiosteoporosis drug or formulation, date they left the plan, or Dec. 31, 2003—whichever came first.

Within 6 months of initiating therapy, 57% of the 9,117 women on weekly therapy and 62% of the 3,421 women on daily therapy were considered to have adherence failure. At 1 year, 66% of those on weekly therapy and 71% of those on daily therapy had adherence failure. At 2.5 years, the rates were 80% for weekly therapy and 82% for daily therapy.

Risk of failure was higher among women aged 65 years and older but lower in those with a fracture history. The researchers did not assess adherence for specific drugs.

The research was funded by Amgen Inc., which is currently investigating a fully monoclonal antibody for osteoporosis.

NASHVILLE, TENN. — Women with postmenopausal osteoporosis are no more likely to adhere to bisphosphonate therapy with weekly dosing than with daily dosing, according to data presented in a poster at the annual meeting of the American Society for Bone and Mineral Research.

In a retrospective study of 12,538 women with postmenopausal osteoporosis, risk of adherence failure did not differ between patients receiving weekly versus daily bisphosphonate therapy, according to Derek Weycker, Ph.D., of Policy Analysis Inc. in Brookline, Mass., and colleagues.

The researchers reviewed integrated medical and outpatient pharmacy claims from 1998 to 2003 for women aged 45 years and older with postmenopausal osteoporosis from 30 U.S. health plans.

Women were said to have postmenopausal osteoporosis if they had one or more medical claims with a corresponding diagnosis code. They also had no evidence of secondary causes of osteoporosis.

Adherence was assessed daily from the date of therapy initiation through the date of a switch to another antiosteoporosis drug or formulation, date they left the plan, or Dec. 31, 2003—whichever came first.

Within 6 months of initiating therapy, 57% of the 9,117 women on weekly therapy and 62% of the 3,421 women on daily therapy were considered to have adherence failure. At 1 year, 66% of those on weekly therapy and 71% of those on daily therapy had adherence failure. At 2.5 years, the rates were 80% for weekly therapy and 82% for daily therapy.

Risk of failure was higher among women aged 65 years and older but lower in those with a fracture history. The researchers did not assess adherence for specific drugs.

The research was funded by Amgen Inc., which is currently investigating a fully monoclonal antibody for osteoporosis.

PORTO, PORTUGAL — Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

The researchers used both visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki. Sixteen patients had mild cognitive impairment (19–23 on the MMSE) and 15 patients had moderate cognitive impairment (11–18 on the MMSE).

EEG was performed for 20 minutes with eyes closed. There was no significant difference between the visual EEG results for the two subcortical vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. Visual EEG results did not correlate with cognitive impairment as measured by the MMSE.

There were significant differences between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment, measured by the MMSE. The cholinergic deficit in subcortical vascular dementia may change bioelectric activity in ways not readily evident on visual inspection of EEG, but the calculational power of quantitative EEG is great enough to pick up these changes.

PORTO, PORTUGAL — Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

The researchers used both visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki. Sixteen patients had mild cognitive impairment (19–23 on the MMSE) and 15 patients had moderate cognitive impairment (11–18 on the MMSE).

EEG was performed for 20 minutes with eyes closed. There was no significant difference between the visual EEG results for the two subcortical vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. Visual EEG results did not correlate with cognitive impairment as measured by the MMSE.

There were significant differences between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment, measured by the MMSE. The cholinergic deficit in subcortical vascular dementia may change bioelectric activity in ways not readily evident on visual inspection of EEG, but the calculational power of quantitative EEG is great enough to pick up these changes.

PORTO, PORTUGAL — Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

The researchers used both visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki. Sixteen patients had mild cognitive impairment (19–23 on the MMSE) and 15 patients had moderate cognitive impairment (11–18 on the MMSE).

EEG was performed for 20 minutes with eyes closed. There was no significant difference between the visual EEG results for the two subcortical vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. Visual EEG results did not correlate with cognitive impairment as measured by the MMSE.

There were significant differences between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment, measured by the MMSE. The cholinergic deficit in subcortical vascular dementia may change bioelectric activity in ways not readily evident on visual inspection of EEG, but the calculational power of quantitative EEG is great enough to pick up these changes.

NASHVILLE, TENN. — Physicians may need to rethink their advice to patients to get some casual sun to ensure vitamin D sufficiency, according to new data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a study of young adults in Hawaii, abundant sun exposure did not guarantee adequate serum levels of vitamin D, said Dr. Neil C. Binkley of the osteoporosis clinical center and research program at the University of Wisconsin in Madison.

“This suggests that some individuals—for an unclear reason or reasons—do not achieve a high circulating D₃ concentration despite abundant sun exposure,” he said. “It seems logical that the clinical approach that many of us take to recommend casual sun exposure for patients is certainly not a guarantee of vitamin D adequacy.”

Initially, individuals with abundant sun exposure were studied in order to identify the upper limit of the normal range of 25-hydroxy vitamin D₃ (25[OH]D₃).

The investigators recruited 100 young adults, most of whom were surfers, from the Honolulu area in March 2005.

Participants were required to have had 3 or more hours of sun exposure per day, 5 or more days per week, for the previous 3 months. Information about sun exposure, sunscreen use, and dietary vitamin D intake was obtained by questionnaire. Skin color was measured by reflectance colorimetry.

Forty-one percent of the cohort used no sunscreen. On average, participants were exposed to the sun for about 4 hours per day, or 28 hours weekly.

This estimate included hours exposed to the sun with sunscreen.

As part of the self-questionnaire, respondents were asked to fill in areas of skin coverage on human figures. The researchers were then able to calculate that the group had an average of 10.6 hours per week of whole-body sun exposure.

A group of 174 healthy controls were recruited from the University of Wisconsin between January and April of 2005. No data were obtained from this group regarding sun exposure, sunscreen use, and dietary vitamin D.

The two groups were similar in terms of average age, 24, and average body mass index, 23. There were slightly more men in the Hawaii cohort (67% vs. 46%).

Serum 25(OH)D₃ was measured by a precise high-performance liquid chromatography assay.

Results correlated well with those obtained by tandem mass spectroscopy.

Using a cutoff of 30 ng/mL to define inadequate vitamin D status—a point of some contention among researchers—86% of the Wisconsin cohort was vitamin D inadequate. And “somewhat surprisingly, 51% of the Hawaii cohort was below this arbitrary cutoff.” The mean concentration of serum 25(OH)D₃ was 31.4 ng/mL in the Hawaii cohort, compared with 18.3 ng/mL in the Wisconsin cohort.

The highest levels of 25(OH)D₃ were almost identical in the Hawaii and Wisconsin groups (62.0 ng/mL vs. 62.3 ng/mL). Levels of 25(OH)D₃ in the Hawaii group were unrelated to hours of sun exposure or skin color.

Among those in the Hawaii cohort, the 10 participants with the lowest serum 25(OH)D₃ levels were similar to the rest of the cohort in terms of parathyroid hormone levels, age, body mass index, serum chemistries, multivitamin use, and number of hours of sun exposure without sunscreen.

They did have a lower average number of hours per week of whole-body sun exposure (6 hours).

Serum vitamin D₃ levels were also measured in a random subset of 20 individuals in the Hawaii cohort. “Despite abundant sun exposure, some of these individuals do not maintain a high serum concentration of D₃,” Dr. Binkley said.

The individuals with the highest 25(OH)D₃ levels in both cohorts had levels slightly higher than 60 ng/mL.

This suggests that the upper limit for normal 25(OH)D₃ levels is 60–80 ng/mL, which is consistent with published reports, Dr. Binkley said.

The results are limited by the self-reporting of sun exposure.

NASHVILLE, TENN. — Physicians may need to rethink their advice to patients to get some casual sun to ensure vitamin D sufficiency, according to new data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a study of young adults in Hawaii, abundant sun exposure did not guarantee adequate serum levels of vitamin D, said Dr. Neil C. Binkley of the osteoporosis clinical center and research program at the University of Wisconsin in Madison.

“This suggests that some individuals—for an unclear reason or reasons—do not achieve a high circulating D₃ concentration despite abundant sun exposure,” he said. “It seems logical that the clinical approach that many of us take to recommend casual sun exposure for patients is certainly not a guarantee of vitamin D adequacy.”

Initially, individuals with abundant sun exposure were studied in order to identify the upper limit of the normal range of 25-hydroxy vitamin D₃ (25[OH]D₃).

The investigators recruited 100 young adults, most of whom were surfers, from the Honolulu area in March 2005.

Participants were required to have had 3 or more hours of sun exposure per day, 5 or more days per week, for the previous 3 months. Information about sun exposure, sunscreen use, and dietary vitamin D intake was obtained by questionnaire. Skin color was measured by reflectance colorimetry.

Forty-one percent of the cohort used no sunscreen. On average, participants were exposed to the sun for about 4 hours per day, or 28 hours weekly.

This estimate included hours exposed to the sun with sunscreen.

As part of the self-questionnaire, respondents were asked to fill in areas of skin coverage on human figures. The researchers were then able to calculate that the group had an average of 10.6 hours per week of whole-body sun exposure.

A group of 174 healthy controls were recruited from the University of Wisconsin between January and April of 2005. No data were obtained from this group regarding sun exposure, sunscreen use, and dietary vitamin D.

The two groups were similar in terms of average age, 24, and average body mass index, 23. There were slightly more men in the Hawaii cohort (67% vs. 46%).

Serum 25(OH)D₃ was measured by a precise high-performance liquid chromatography assay.

Results correlated well with those obtained by tandem mass spectroscopy.

Using a cutoff of 30 ng/mL to define inadequate vitamin D status—a point of some contention among researchers—86% of the Wisconsin cohort was vitamin D inadequate. And “somewhat surprisingly, 51% of the Hawaii cohort was below this arbitrary cutoff.” The mean concentration of serum 25(OH)D₃ was 31.4 ng/mL in the Hawaii cohort, compared with 18.3 ng/mL in the Wisconsin cohort.

The highest levels of 25(OH)D₃ were almost identical in the Hawaii and Wisconsin groups (62.0 ng/mL vs. 62.3 ng/mL). Levels of 25(OH)D₃ in the Hawaii group were unrelated to hours of sun exposure or skin color.

Among those in the Hawaii cohort, the 10 participants with the lowest serum 25(OH)D₃ levels were similar to the rest of the cohort in terms of parathyroid hormone levels, age, body mass index, serum chemistries, multivitamin use, and number of hours of sun exposure without sunscreen.

They did have a lower average number of hours per week of whole-body sun exposure (6 hours).

Serum vitamin D₃ levels were also measured in a random subset of 20 individuals in the Hawaii cohort. “Despite abundant sun exposure, some of these individuals do not maintain a high serum concentration of D₃,” Dr. Binkley said.

The individuals with the highest 25(OH)D₃ levels in both cohorts had levels slightly higher than 60 ng/mL.

This suggests that the upper limit for normal 25(OH)D₃ levels is 60–80 ng/mL, which is consistent with published reports, Dr. Binkley said.

The results are limited by the self-reporting of sun exposure.

NASHVILLE, TENN. — Physicians may need to rethink their advice to patients to get some casual sun to ensure vitamin D sufficiency, according to new data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a study of young adults in Hawaii, abundant sun exposure did not guarantee adequate serum levels of vitamin D, said Dr. Neil C. Binkley of the osteoporosis clinical center and research program at the University of Wisconsin in Madison.

“This suggests that some individuals—for an unclear reason or reasons—do not achieve a high circulating D₃ concentration despite abundant sun exposure,” he said. “It seems logical that the clinical approach that many of us take to recommend casual sun exposure for patients is certainly not a guarantee of vitamin D adequacy.”

Initially, individuals with abundant sun exposure were studied in order to identify the upper limit of the normal range of 25-hydroxy vitamin D₃ (25[OH]D₃).

The investigators recruited 100 young adults, most of whom were surfers, from the Honolulu area in March 2005.

Participants were required to have had 3 or more hours of sun exposure per day, 5 or more days per week, for the previous 3 months. Information about sun exposure, sunscreen use, and dietary vitamin D intake was obtained by questionnaire. Skin color was measured by reflectance colorimetry.

Forty-one percent of the cohort used no sunscreen. On average, participants were exposed to the sun for about 4 hours per day, or 28 hours weekly.

This estimate included hours exposed to the sun with sunscreen.

As part of the self-questionnaire, respondents were asked to fill in areas of skin coverage on human figures. The researchers were then able to calculate that the group had an average of 10.6 hours per week of whole-body sun exposure.

A group of 174 healthy controls were recruited from the University of Wisconsin between January and April of 2005. No data were obtained from this group regarding sun exposure, sunscreen use, and dietary vitamin D.

The two groups were similar in terms of average age, 24, and average body mass index, 23. There were slightly more men in the Hawaii cohort (67% vs. 46%).

Serum 25(OH)D₃ was measured by a precise high-performance liquid chromatography assay.

Results correlated well with those obtained by tandem mass spectroscopy.

Using a cutoff of 30 ng/mL to define inadequate vitamin D status—a point of some contention among researchers—86% of the Wisconsin cohort was vitamin D inadequate. And “somewhat surprisingly, 51% of the Hawaii cohort was below this arbitrary cutoff.” The mean concentration of serum 25(OH)D₃ was 31.4 ng/mL in the Hawaii cohort, compared with 18.3 ng/mL in the Wisconsin cohort.

The highest levels of 25(OH)D₃ were almost identical in the Hawaii and Wisconsin groups (62.0 ng/mL vs. 62.3 ng/mL). Levels of 25(OH)D₃ in the Hawaii group were unrelated to hours of sun exposure or skin color.

Among those in the Hawaii cohort, the 10 participants with the lowest serum 25(OH)D₃ levels were similar to the rest of the cohort in terms of parathyroid hormone levels, age, body mass index, serum chemistries, multivitamin use, and number of hours of sun exposure without sunscreen.

They did have a lower average number of hours per week of whole-body sun exposure (6 hours).

Serum vitamin D₃ levels were also measured in a random subset of 20 individuals in the Hawaii cohort. “Despite abundant sun exposure, some of these individuals do not maintain a high serum concentration of D₃,” Dr. Binkley said.

The individuals with the highest 25(OH)D₃ levels in both cohorts had levels slightly higher than 60 ng/mL.

This suggests that the upper limit for normal 25(OH)D₃ levels is 60–80 ng/mL, which is consistent with published reports, Dr. Binkley said.

The results are limited by the self-reporting of sun exposure.

BALTIMORE – Depression frequently co-occurs with eating disorders, making treatment challenging, Dr. Graham W. Redgrave said at a symposium on mood disorders sponsored by Johns Hopkins University.

“There are high rates of concurrent major depressive disorder in anorexia,” said Dr. Redgrave of the Johns Hopkins University in Baltimore. Among patients with the restricting type of anorexia, 15%–50% also have major depressive disorder (MDD). The rates among patients with the binge-eating/purging type of anorexia are even higher at 46%–80%. The rates are higher still when these patients are asked whether they have ever had depression.

Numbers like these suggest that anorexia might simply be a behavioral manifestation of an underlying mood disorder. However, controlled family studies have provided good evidence that these disorders are different and independent, Dr. Redgrave said.

One reason so much overlap exists between anorexia and MDD is that starvation produces a host of psychiatric conditions in the body, such as mood lability, irritability, anxiety, apathy, obsessiveness, poor concentration, social withdrawal, and decreased libido.

Patients with anorexia aren't the only ones suffering from comorbid depression. Among patients with bulimia, 30%–60% have concurrent MDD and 50%–65% have had a lifetime occurrence of depression.

In patients with bulimia, starvation can magnify feelings of guilt, shame, and hopelessness, Dr. Redgrave said. Increased frequency in the binge and purge cycles decreases the ability to concentrate, because the fear of being overweight increases in importance.

Depression also is high among patients with binge-eating disorder, with 36%–60% of these patients also having MDD. In addition, 48% of obese women who binge also have MDD, compared with only 26% of obese women who do not binge. “It's not just the obesity. There's something about the psychopathology of depression and the binge eating that seems to be related,” Dr. Redgrave said.

Treatment of patients with eating disorders and depression can be a challenge because “when you are treating an eating disorder, you are asking your patient to give up something that is very rewarding,” he said. Patients can recognize that what they're doing is problematic but have a hard time giving it up.

“Imagine if you have a parallel mood disorder that is making your thoughts about yourself more hopeless and self-deprecating. … How much harder would it be to give up behavior that is rewarding?”, Dr. Redgrave said at the symposium, also sponsored by the Depression and Related Affective Disorders Association.

Treatment for an eating disorder focuses first on behaviors and then on thoughts and feelings. Underlying connections and associations are addressed only when the patient is stabilized. When the patient's health is in jeopardy, “you can't be worried about why this happened, you just have to fix it, and then worry about the why,” he said.

Pharmacotherapy is primarily an adjunctive treatment for patients with anorexia. Antidepressants are of modest but important benefit in bulimia nervosa, Dr. Redgrave said. Fluoxetine at high doses is especially useful, though most antidepressants can be useful in this population. Bupropion is contraindicated because of the risk of seizures.

BALTIMORE – Depression frequently co-occurs with eating disorders, making treatment challenging, Dr. Graham W. Redgrave said at a symposium on mood disorders sponsored by Johns Hopkins University.

“There are high rates of concurrent major depressive disorder in anorexia,” said Dr. Redgrave of the Johns Hopkins University in Baltimore. Among patients with the restricting type of anorexia, 15%–50% also have major depressive disorder (MDD). The rates among patients with the binge-eating/purging type of anorexia are even higher at 46%–80%. The rates are higher still when these patients are asked whether they have ever had depression.

Numbers like these suggest that anorexia might simply be a behavioral manifestation of an underlying mood disorder. However, controlled family studies have provided good evidence that these disorders are different and independent, Dr. Redgrave said.

One reason so much overlap exists between anorexia and MDD is that starvation produces a host of psychiatric conditions in the body, such as mood lability, irritability, anxiety, apathy, obsessiveness, poor concentration, social withdrawal, and decreased libido.

Patients with anorexia aren't the only ones suffering from comorbid depression. Among patients with bulimia, 30%–60% have concurrent MDD and 50%–65% have had a lifetime occurrence of depression.

In patients with bulimia, starvation can magnify feelings of guilt, shame, and hopelessness, Dr. Redgrave said. Increased frequency in the binge and purge cycles decreases the ability to concentrate, because the fear of being overweight increases in importance.

Depression also is high among patients with binge-eating disorder, with 36%–60% of these patients also having MDD. In addition, 48% of obese women who binge also have MDD, compared with only 26% of obese women who do not binge. “It's not just the obesity. There's something about the psychopathology of depression and the binge eating that seems to be related,” Dr. Redgrave said.

Treatment of patients with eating disorders and depression can be a challenge because “when you are treating an eating disorder, you are asking your patient to give up something that is very rewarding,” he said. Patients can recognize that what they're doing is problematic but have a hard time giving it up.

“Imagine if you have a parallel mood disorder that is making your thoughts about yourself more hopeless and self-deprecating. … How much harder would it be to give up behavior that is rewarding?”, Dr. Redgrave said at the symposium, also sponsored by the Depression and Related Affective Disorders Association.

Treatment for an eating disorder focuses first on behaviors and then on thoughts and feelings. Underlying connections and associations are addressed only when the patient is stabilized. When the patient's health is in jeopardy, “you can't be worried about why this happened, you just have to fix it, and then worry about the why,” he said.

Pharmacotherapy is primarily an adjunctive treatment for patients with anorexia. Antidepressants are of modest but important benefit in bulimia nervosa, Dr. Redgrave said. Fluoxetine at high doses is especially useful, though most antidepressants can be useful in this population. Bupropion is contraindicated because of the risk of seizures.

BALTIMORE – Depression frequently co-occurs with eating disorders, making treatment challenging, Dr. Graham W. Redgrave said at a symposium on mood disorders sponsored by Johns Hopkins University.

“There are high rates of concurrent major depressive disorder in anorexia,” said Dr. Redgrave of the Johns Hopkins University in Baltimore. Among patients with the restricting type of anorexia, 15%–50% also have major depressive disorder (MDD). The rates among patients with the binge-eating/purging type of anorexia are even higher at 46%–80%. The rates are higher still when these patients are asked whether they have ever had depression.

Numbers like these suggest that anorexia might simply be a behavioral manifestation of an underlying mood disorder. However, controlled family studies have provided good evidence that these disorders are different and independent, Dr. Redgrave said.

One reason so much overlap exists between anorexia and MDD is that starvation produces a host of psychiatric conditions in the body, such as mood lability, irritability, anxiety, apathy, obsessiveness, poor concentration, social withdrawal, and decreased libido.

Patients with anorexia aren't the only ones suffering from comorbid depression. Among patients with bulimia, 30%–60% have concurrent MDD and 50%–65% have had a lifetime occurrence of depression.

In patients with bulimia, starvation can magnify feelings of guilt, shame, and hopelessness, Dr. Redgrave said. Increased frequency in the binge and purge cycles decreases the ability to concentrate, because the fear of being overweight increases in importance.

Depression also is high among patients with binge-eating disorder, with 36%–60% of these patients also having MDD. In addition, 48% of obese women who binge also have MDD, compared with only 26% of obese women who do not binge. “It's not just the obesity. There's something about the psychopathology of depression and the binge eating that seems to be related,” Dr. Redgrave said.

Treatment of patients with eating disorders and depression can be a challenge because “when you are treating an eating disorder, you are asking your patient to give up something that is very rewarding,” he said. Patients can recognize that what they're doing is problematic but have a hard time giving it up.

“Imagine if you have a parallel mood disorder that is making your thoughts about yourself more hopeless and self-deprecating. … How much harder would it be to give up behavior that is rewarding?”, Dr. Redgrave said at the symposium, also sponsored by the Depression and Related Affective Disorders Association.

Treatment for an eating disorder focuses first on behaviors and then on thoughts and feelings. Underlying connections and associations are addressed only when the patient is stabilized. When the patient's health is in jeopardy, “you can't be worried about why this happened, you just have to fix it, and then worry about the why,” he said.

Pharmacotherapy is primarily an adjunctive treatment for patients with anorexia. Antidepressants are of modest but important benefit in bulimia nervosa, Dr. Redgrave said. Fluoxetine at high doses is especially useful, though most antidepressants can be useful in this population. Bupropion is contraindicated because of the risk of seizures.

PORTO, PORTUGAL – Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

“Quantitative EEG results correlated strongly with mental impairment in subcortical vascular dementia,” said Dr. Malgorzata Gawel, of the Medical University of Warsaw.

The white matter lesions and lacunar ischemic stroke that are associated with subclinical vascular dementia lead to the destruction of neurons and neuronal synapses and also cause cholinergic deficits. In turn, cholinergic deficits lead to changes in synaptic bioelectric potential, which may be picked up in EEG signals. In particular, these changes result in a slowing of background brain activity and the presence of slow brain waves (delta and theta), Dr. Gawel said.

The researchers used visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki.

The group with dementia was further divided into two subgroups based on severity of cognitive impairment. The first group (16 patients) had mild cognitive impairment, defined as a score of 19–23 on the Mini-Mental State Examination (MMSE). The second group (15 patients) had moderate cognitive impairment, defined as a score of 11–18 on the MMSE.

EEG was performed for 20 minutes with eyes closed. Visual inspection of EEGs involved an 8-point scale, with 1 being normal and 8 representing severe abnormalities. There was no significant difference between visual EEG results for the two vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. There was no correlation between visual EEG results and cognitive impairment measured by the MMSE.

Quantitative EEG was performed for 5 minutes, following the visual EEG. The researchers calculated the power ratio of alpha waves to theta waves (A/T); the ratio of alpha waves to delta waves (A/D); and the ratio of alpha waves to the sum of theta and delta waves (A/T+D). They also calculated the mean waves frequency for all derivations (amplifier/electrode configurations), with particular interest in the occiptal and temporal derivations.

There was significant difference between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment.

PORTO, PORTUGAL – Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

“Quantitative EEG results correlated strongly with mental impairment in subcortical vascular dementia,” said Dr. Malgorzata Gawel, of the Medical University of Warsaw.

The white matter lesions and lacunar ischemic stroke that are associated with subclinical vascular dementia lead to the destruction of neurons and neuronal synapses and also cause cholinergic deficits. In turn, cholinergic deficits lead to changes in synaptic bioelectric potential, which may be picked up in EEG signals. In particular, these changes result in a slowing of background brain activity and the presence of slow brain waves (delta and theta), Dr. Gawel said.

The researchers used visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki.

The group with dementia was further divided into two subgroups based on severity of cognitive impairment. The first group (16 patients) had mild cognitive impairment, defined as a score of 19–23 on the Mini-Mental State Examination (MMSE). The second group (15 patients) had moderate cognitive impairment, defined as a score of 11–18 on the MMSE.

EEG was performed for 20 minutes with eyes closed. Visual inspection of EEGs involved an 8-point scale, with 1 being normal and 8 representing severe abnormalities. There was no significant difference between visual EEG results for the two vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. There was no correlation between visual EEG results and cognitive impairment measured by the MMSE.

Quantitative EEG was performed for 5 minutes, following the visual EEG. The researchers calculated the power ratio of alpha waves to theta waves (A/T); the ratio of alpha waves to delta waves (A/D); and the ratio of alpha waves to the sum of theta and delta waves (A/T+D). They also calculated the mean waves frequency for all derivations (amplifier/electrode configurations), with particular interest in the occiptal and temporal derivations.

There was significant difference between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment.

PORTO, PORTUGAL – Quantitative EEG shows promise as a clinical diagnostic tool that is sensitive enough to distinguish mild from moderate subcortical dementia, according to one study presented at the Fourth International Congress on Vascular Dementia.

“Quantitative EEG results correlated strongly with mental impairment in subcortical vascular dementia,” said Dr. Malgorzata Gawel, of the Medical University of Warsaw.

The white matter lesions and lacunar ischemic stroke that are associated with subclinical vascular dementia lead to the destruction of neurons and neuronal synapses and also cause cholinergic deficits. In turn, cholinergic deficits lead to changes in synaptic bioelectric potential, which may be picked up in EEG signals. In particular, these changes result in a slowing of background brain activity and the presence of slow brain waves (delta and theta), Dr. Gawel said.

The researchers used visual and quantitative EEG to evaluate 31 patients with subcortical vascular dementia (mean age 72 years, 19 women) and 14 healthy controls (mean age 70 years, 8 women). Subcortical vascular dementia was diagnosed using the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and criteria developed by Timo Erkinjuntti of the University of Helsinki.

The group with dementia was further divided into two subgroups based on severity of cognitive impairment. The first group (16 patients) had mild cognitive impairment, defined as a score of 19–23 on the Mini-Mental State Examination (MMSE). The second group (15 patients) had moderate cognitive impairment, defined as a score of 11–18 on the MMSE.

EEG was performed for 20 minutes with eyes closed. Visual inspection of EEGs involved an 8-point scale, with 1 being normal and 8 representing severe abnormalities. There was no significant difference between visual EEG results for the two vascular dementia subgroups. There was a significant difference on the visual EEG results between the control group and both subcortical vascular dementia subgroups. There was no correlation between visual EEG results and cognitive impairment measured by the MMSE.

Quantitative EEG was performed for 5 minutes, following the visual EEG. The researchers calculated the power ratio of alpha waves to theta waves (A/T); the ratio of alpha waves to delta waves (A/D); and the ratio of alpha waves to the sum of theta and delta waves (A/T+D). They also calculated the mean waves frequency for all derivations (amplifier/electrode configurations), with particular interest in the occiptal and temporal derivations.

There was significant difference between the quantitative EEG results for the patients with mild and moderate dementia for all parameters. There was a significant correlation between all parameters and cognitive impairment.

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Akihiko Nunomura, M.D., of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) who had been previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were performed on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β 42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Akihiko Nunomura, M.D., of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) who had been previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were performed on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β 42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

PORTO, PORTUGAL — The hallmark amyloid accumulation in Alzheimer's disease may actually be the body's response to neuronal oxidative stress, according to data presented at the Fourth International Congress on Vascular Dementia.

Attempts to remove amyloid plaque may have the unintended effect of increasing neuronal oxidative damage, said Akihiko Nunomura, M.D., of Asahikawa (Japan) Medical College.

Evaluation of immunoreactions in the hippocampal regions of the brains of patients with Alzheimer's disease (AD) has revealed an inverse relationship between amyloid-β 42—the protein believed to be responsible for the formation of amyloid plaques in the brain—and the nucleoside 8-hydroxyguanosine—a product of RNA oxidation that serves as a biomarker of neuronal oxidative stress, he said.

Dr. Nunomura and his colleagues evaluated postmortem tissue samples from the hippocampal region of 16 subjects (aged 65–93 years at time of death) who had been previously diagnosed with AD using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Optical density measurements were performed on tissue samples that had been immunochemically stained for 8-hydroxyguanosine, amyloid-β 40, and amyloid-β 42.

Intraneuronal amyloid-β 42 and 8-hydroxyguanosine immunoreactions were observed in the hippocampal pyramidal neurons in all of the subjects. Neurons positive for 8-hydroxyguanosine were more widely distributed compared with those positive for amyloid-β 42. However, immunoreaction of intraneuronal amyloid-β 40 was faint in most of the subjects, compared with that of amyloid-β 42.

“When we focused on the relationship between intraneuronal 8-hydroxyguanosine and amyloid-β 42 immunoreactivities, we found several cases with high 8-hydroxyguanosine and low amyloid-β 42, as well as [several cases with] low 8-hydroxyguanosine and high amyloid-β 42,” said Dr. Nunomura.

Relative optical density measurements confirmed the inverse relationship between 8-hydroxyguanosine and amyloid-β 42 immunoreactivities but there was no significant relationship between 8-hydroxyguanosine and amyloid-β 40.

The inverse relationship between 8-hydroxyguanosine and amyloid-β 42 suggests “that extra- and intraneuronal accumulation of amyloid-β 42 is related to a compensatory response to neuronal oxidative stress in AD,” said Dr. Nunomura.

While the mechanism at work is unclear, the researchers hypothesize that amyloid-β 42 accumulates as a response to oxidative stress and that 8-hydroxyguanosine is also downregulated, coauthor George Perry, Ph.D., said in an interview. Dr. Perry is a professor of pathology and neurosciences and Case Western Reserve University in Cleveland.

The researchers previously reported an inverse relationship between percent area of amyloid-β 42 plaque burden and immunointensity of neuronal 8-hydroxyguanosine in subjects with Down syndrome. In addition, both intraneuronal amyloid-β accumulation and oxidative stress precede amyloid-β deposition both in patients with Down syndrome and in transgenic mice models of AD.

Taken together with previous data, these findings suggest that excessive removal of amyloid-β may lead to increased neuronal oxidative damage in AD, said Dr. Nunomura.

Faint intraneuronal A-β 42 immunoreactivity in the hippocampus is shown in an 82-year old AD patient (left). Intense intraneuronal A-β 42 immunoreactivity in a 77-year-old patient with AD (right). Arrow indicates extraneuronal A-β deposition. Photos courtesy Dr. Akihiko Nunomura

PORTO, PORTUGAL — Cerebral amyloid angiopathy appears to disproportionately affect the occipital region, according to findings presented at the Fourth International Congress on Vascular Dementia.

In a study involving the postmortem neuropathologic evaluation of brains from 113 subjects (61% women), the incidence and severity of cerebral amyloid angiopathy (CAA) was highest in the occipital region, followed by the frontal, hippocampal, and frontobasal areas. The occipital region was significantly more frequently and more severely affected than the other regions, said Johannes Attems, M.D., of the Otto Wagner Hospital in Vienna.

Cerebral amyloid angiopathy (CAA) is defined by the deposition of amyloid-β peptide in cerebral vessels and has been associated with Alzheimer's disease (AD). Despite the association with AD, CAA has been shown to be an independent risk factor for cognitive decline.

Dr. Attems and his colleagues looked at the topographical distribution of CAA in the vessels of the brain, as well as the relationship between CAA and AD. In all, 63 patients had a clinical diagnosis of dementia and 50 were nondemented. Dementia was assessed retrospectively from hospital charts based on ICD-10 criteria of a Mini-Mental State Examination score less than 20. Subjects ranged in age from 54 to 102 years at the time of death.

Neuropathologic assessment of AD was performed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria, Braak stages, and National Institute on Aging/Reagan Institute (NIA-Reagan) criteria. In this cohort, 43 subjects had high-grade AD pathology, 16 with medium-grade AD pathology, 37 with low-grade AD pathology, and 17 with no AD pathology.

Sections were immunostained with modified Bielschowsky silver stain and a commercially available monoclonal human amyloid-β antibody for the detection of amyloid-β in cerebral vessels. The severity of amyloid-β deposition in vessels—and CAA—was semiquantitatively assessed in the frontal, frontobasal, hippocampal, and occipital regions. The researchers used a 5-point scoring system. A grade of 0 signified no amyloid-β was present, while grade 4 signified severe amyloid-β deposition.

Within a region, scores were totaled separately for meningeal and cortical vessels. These values were totaled for a regional score. A mean overall score was then calculated using the regional values. For a better estimate of the relative contribution of the separate regional scores, the overall score was subtracted from each regional score to yield relative scores.

CAA was present in 77 cases. In these subjects, “Independent of the region, meningeal vessels were always affected more frequently and more severely than cortical vessels,” said Dr. Attems. However, the differences between meningeal and cortical vessels were only statistically significant in the occipital region.

“CAA prevalence was significantly higher in cases with high-grade AD pathology, compared with cases with no to medium pathology,” said Dr. Attems. Overall CAA severity increased with increasing AD pathology. This was true in all of the regions, though only the relative contribution of CAA in the occipital region increases significantly with increasing AD pathology.

“This means that—at least statistically—increasing AD pathology shifts the topographic distribution of CAA even more toward the occipital cortex,” said Dr. Attems.

Interestingly, of the brains with no AD pathology, 24% had evidence of CAA. Conversely, 24% of brains with AD pathology showed no evidence of CAA. “We have cases with severe CAA but without any AD pathology and on the other hand, case with high AD pathology completely lacking CAA,” said Dr. Attems. This suggests that neuritic AD pathology and CAA might represent different entities.

Demented subjects more frequently showed signs of CAA and CAA total scores were greater than in nondemented patients. This finding suggests a significant association between CAA and dementia, said Dr. Attems. However, after controlling for clinical criteria, the association was no longer statistically significant.

“The combination of AD pathology and CAA might synergistically contribute to the development of clinical dementia,” said Dr. Attems.

Interestingly, among patients with a CAA total score greater than 0, there was no difference in the prevalence of CAA between cases with high versus low AD pathology. Also the CAA total score did not increase with increasing AD pathology in this subgroup.

Immunostaining of tissue with cerebral amyloid angiopathy using modified Bielschowsky silver stain shows severe thickening of the cortical vessel walls. Courtesy Dr. Johannes Attems

PORTO, PORTUGAL — Cerebral amyloid angiopathy appears to disproportionately affect the occipital region, according to findings presented at the Fourth International Congress on Vascular Dementia.

In a study involving the postmortem neuropathologic evaluation of brains from 113 subjects (61% women), the incidence and severity of cerebral amyloid angiopathy (CAA) was highest in the occipital region, followed by the frontal, hippocampal, and frontobasal areas. The occipital region was significantly more frequently and more severely affected than the other regions, said Johannes Attems, M.D., of the Otto Wagner Hospital in Vienna.

Cerebral amyloid angiopathy (CAA) is defined by the deposition of amyloid-β peptide in cerebral vessels and has been associated with Alzheimer's disease (AD). Despite the association with AD, CAA has been shown to be an independent risk factor for cognitive decline.

Dr. Attems and his colleagues looked at the topographical distribution of CAA in the vessels of the brain, as well as the relationship between CAA and AD. In all, 63 patients had a clinical diagnosis of dementia and 50 were nondemented. Dementia was assessed retrospectively from hospital charts based on ICD-10 criteria of a Mini-Mental State Examination score less than 20. Subjects ranged in age from 54 to 102 years at the time of death.

Neuropathologic assessment of AD was performed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria, Braak stages, and National Institute on Aging/Reagan Institute (NIA-Reagan) criteria. In this cohort, 43 subjects had high-grade AD pathology, 16 with medium-grade AD pathology, 37 with low-grade AD pathology, and 17 with no AD pathology.

Sections were immunostained with modified Bielschowsky silver stain and a commercially available monoclonal human amyloid-β antibody for the detection of amyloid-β in cerebral vessels. The severity of amyloid-β deposition in vessels—and CAA—was semiquantitatively assessed in the frontal, frontobasal, hippocampal, and occipital regions. The researchers used a 5-point scoring system. A grade of 0 signified no amyloid-β was present, while grade 4 signified severe amyloid-β deposition.

Within a region, scores were totaled separately for meningeal and cortical vessels. These values were totaled for a regional score. A mean overall score was then calculated using the regional values. For a better estimate of the relative contribution of the separate regional scores, the overall score was subtracted from each regional score to yield relative scores.

CAA was present in 77 cases. In these subjects, “Independent of the region, meningeal vessels were always affected more frequently and more severely than cortical vessels,” said Dr. Attems. However, the differences between meningeal and cortical vessels were only statistically significant in the occipital region.

“CAA prevalence was significantly higher in cases with high-grade AD pathology, compared with cases with no to medium pathology,” said Dr. Attems. Overall CAA severity increased with increasing AD pathology. This was true in all of the regions, though only the relative contribution of CAA in the occipital region increases significantly with increasing AD pathology.

“This means that—at least statistically—increasing AD pathology shifts the topographic distribution of CAA even more toward the occipital cortex,” said Dr. Attems.

Interestingly, of the brains with no AD pathology, 24% had evidence of CAA. Conversely, 24% of brains with AD pathology showed no evidence of CAA. “We have cases with severe CAA but without any AD pathology and on the other hand, case with high AD pathology completely lacking CAA,” said Dr. Attems. This suggests that neuritic AD pathology and CAA might represent different entities.

Demented subjects more frequently showed signs of CAA and CAA total scores were greater than in nondemented patients. This finding suggests a significant association between CAA and dementia, said Dr. Attems. However, after controlling for clinical criteria, the association was no longer statistically significant.

“The combination of AD pathology and CAA might synergistically contribute to the development of clinical dementia,” said Dr. Attems.

Interestingly, among patients with a CAA total score greater than 0, there was no difference in the prevalence of CAA between cases with high versus low AD pathology. Also the CAA total score did not increase with increasing AD pathology in this subgroup.

Immunostaining of tissue with cerebral amyloid angiopathy using modified Bielschowsky silver stain shows severe thickening of the cortical vessel walls. Courtesy Dr. Johannes Attems

PORTO, PORTUGAL — Cerebral amyloid angiopathy appears to disproportionately affect the occipital region, according to findings presented at the Fourth International Congress on Vascular Dementia.

In a study involving the postmortem neuropathologic evaluation of brains from 113 subjects (61% women), the incidence and severity of cerebral amyloid angiopathy (CAA) was highest in the occipital region, followed by the frontal, hippocampal, and frontobasal areas. The occipital region was significantly more frequently and more severely affected than the other regions, said Johannes Attems, M.D., of the Otto Wagner Hospital in Vienna.

Cerebral amyloid angiopathy (CAA) is defined by the deposition of amyloid-β peptide in cerebral vessels and has been associated with Alzheimer's disease (AD). Despite the association with AD, CAA has been shown to be an independent risk factor for cognitive decline.

Dr. Attems and his colleagues looked at the topographical distribution of CAA in the vessels of the brain, as well as the relationship between CAA and AD. In all, 63 patients had a clinical diagnosis of dementia and 50 were nondemented. Dementia was assessed retrospectively from hospital charts based on ICD-10 criteria of a Mini-Mental State Examination score less than 20. Subjects ranged in age from 54 to 102 years at the time of death.

Neuropathologic assessment of AD was performed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria, Braak stages, and National Institute on Aging/Reagan Institute (NIA-Reagan) criteria. In this cohort, 43 subjects had high-grade AD pathology, 16 with medium-grade AD pathology, 37 with low-grade AD pathology, and 17 with no AD pathology.

Sections were immunostained with modified Bielschowsky silver stain and a commercially available monoclonal human amyloid-β antibody for the detection of amyloid-β in cerebral vessels. The severity of amyloid-β deposition in vessels—and CAA—was semiquantitatively assessed in the frontal, frontobasal, hippocampal, and occipital regions. The researchers used a 5-point scoring system. A grade of 0 signified no amyloid-β was present, while grade 4 signified severe amyloid-β deposition.

Within a region, scores were totaled separately for meningeal and cortical vessels. These values were totaled for a regional score. A mean overall score was then calculated using the regional values. For a better estimate of the relative contribution of the separate regional scores, the overall score was subtracted from each regional score to yield relative scores.

CAA was present in 77 cases. In these subjects, “Independent of the region, meningeal vessels were always affected more frequently and more severely than cortical vessels,” said Dr. Attems. However, the differences between meningeal and cortical vessels were only statistically significant in the occipital region.

“CAA prevalence was significantly higher in cases with high-grade AD pathology, compared with cases with no to medium pathology,” said Dr. Attems. Overall CAA severity increased with increasing AD pathology. This was true in all of the regions, though only the relative contribution of CAA in the occipital region increases significantly with increasing AD pathology.

“This means that—at least statistically—increasing AD pathology shifts the topographic distribution of CAA even more toward the occipital cortex,” said Dr. Attems.

Interestingly, of the brains with no AD pathology, 24% had evidence of CAA. Conversely, 24% of brains with AD pathology showed no evidence of CAA. “We have cases with severe CAA but without any AD pathology and on the other hand, case with high AD pathology completely lacking CAA,” said Dr. Attems. This suggests that neuritic AD pathology and CAA might represent different entities.

Demented subjects more frequently showed signs of CAA and CAA total scores were greater than in nondemented patients. This finding suggests a significant association between CAA and dementia, said Dr. Attems. However, after controlling for clinical criteria, the association was no longer statistically significant.

“The combination of AD pathology and CAA might synergistically contribute to the development of clinical dementia,” said Dr. Attems.

Interestingly, among patients with a CAA total score greater than 0, there was no difference in the prevalence of CAA between cases with high versus low AD pathology. Also the CAA total score did not increase with increasing AD pathology in this subgroup.

Immunostaining of tissue with cerebral amyloid angiopathy using modified Bielschowsky silver stain shows severe thickening of the cortical vessel walls. Courtesy Dr. Johannes Attems