Alzheimer's Association International Conference 2012 (AAIC)

VANCOUVER, B.C. – Mild cognitive impairment warrants clinical attention as it confers a sharply elevated risk of death and also portends increasing social isolation, according to a pair of longitudinal studies.

Amnestic MCI Is Independent Risk Factor for Death

In the first study, investigators led by Mindy J. Katz, a senior associate in the neurology department of the Albert Einstein College of Medicine, New York, followed 733 community-dwelling participants aged 70 years or older from the Einstein Aging Study.

Susan London/IMNG Medical Media

Results showed that after confounders were taken into account, individuals with the amnestic type of mild cognitive impairment (MCI), which affects memory, were more than twice as likely to die in the next 5 years as were their cognitively intact counterparts. But those with nonamnestic MCI, which affects executive function, judgment, visuospatial ability, and/or language, were not at increased risk.

The heightened mortality with the former may be related both to its frequent progression to Alzheimer’s disease and to its impact on adherence to medical therapy for comorbidities such as hypertension and diabetes, according to Ms. Katz. "If they can’t remember to take their medications, if they don’t keep their appointments with their doctors, their medical care might not be as good as that of someone who is ... capable of keeping these appointments and taking their medications," she said in an interview at the Alzheimer’s Association International Conference 2012.

The findings apply only to people who meet diagnostic criteria for amnestic MCI, she stressed. "Just because you forget where you put your keys or you can’t remember why you walked into a room, that’s not a reason to panic." However, "after you’ve been clinically evaluated and the clinician feels that you really do have a true memory impairment, then it’s a warning sign for both the individual to prepare for the future and for caretakers to be aware that maybe this person might need more care or a plan for care in the future, and to make provisions both financially and in terms of caretaking that might be involved going forward for that individual."

Susan London/IMNG Medical Media

Senior author Dr. Richard B. Lipton, also of the Albert Einstein College of Medicine, noted that there has been some question as to whether MCI is an important entity. "Well, if it’s associated with an increased risk of death, then presumably it’s important, because death is the ultimate hard end point that is face-valid to all parties," he said.

Identifying MCI is now key for two reasons, according to Dr. Lipton. "Ultimately ... that will be a group that’s treated to keep them from progressing and developing full-blown Alzheimer’s disease. But even today, it’s important because adherence to medical therapy for people with memory impairment requires planning and family support."

In the study, 10% of participants had amnestic MCI and 9% had nonamnestic MCI at baseline. Additionally, 3% developed dementia at some time after their first evaluation.

During follow-up, nearly a third of study participants died. In a multivariate analysis, those with amnestic MCI had a significantly elevated risk of death relative to their cognitively intact peers (hazard ratio, 2.17). The other significant independent risk factors were dementia (3.26), advancing age (1.10), Geriatric Depression Scale score (1.09), and comorbidity index (1.34).

In contrast, nonamnestic MCI did not significantly affect risk, nor did educational attainment. APOE e4 allele status showed a trend toward increased mortality.

Withdrawal From Community Life

In the second study, a team led by Dr. Jeffrey Kaye of Oregon Health and Science University in Portland followed 140 community-dwelling, nondepressed older adults from the Intelligent Systems for Assessing Aging Change (ISAAC) cohort who had a mean age of 84 years at baseline.

Susan London/IMNG Medical Media

The investigators used new technology called pervasive computing or embedded ambient sensing, outfitting the participants’ homes with motion sensors and with contact sensors on doors to detect 24/7 activity patterns, including travel outside the home.

At baseline, the 20% of participants who had MCI were statistically indistinguishable from their cognitively intact counterparts in terms of the amount of time spent outside the home each day, with both averaging about 4.2 hours daily.

However, during a follow-up period of more than 3 years, there was a steady decline in this measure in the adults with MCI, compared with little change in the cognitively intact participants. In the last month of monitoring, the participants with MCI left their home for 2.9 hours daily on average, which was significantly shorter than the 3.8 hours recorded for cognitively intact participants.

"With progression of MCI, there is increasingly less time spent outside the home, and it’s independent of mood or health status, so it’s not simply because they are depressed or they are sicker," Dr. Kaye noted in an interview at the conference. "It seems to be more intrinsically a part of having MCI. This to us suggests that there is a progressive narrowing of opportunity to interact with the outside world."

The community withdrawal seen in the MCI group might occur for several reasons. "One of the highest suspicions is that as you develop increasing difficulty with your memory and thinking, you become less confident and more apprehensive about interacting with other people," he proposed. "There may also be just the practical forgetting of appointments and just not attending to things that they would usually be doing. So they are just not remembering to remember."

The participants with MCI were unaware of the change in their activity, according to Dr. Kaye. "We asked them on an annual basis about their activities, and this is very subtle. They don’t actually see this, at least using a sort of subjectively reported series of questions that were asked about their participation in clubs, classes, and social events, and going out to eat, things like that."

By enabling more accurate assessment of time spent outside the home, the technology used could have implications for both clinical care and research.

"For those of us interested in trying to get more real-time measurement of activity and behavior, we think that this kind of measure can be used to unobtrusively assess very early activity changes that may be indicative of evolving MCI," he explained. "It would be much more meaningful, rather than saying, ‘I remembered one more animal on that memory test’ [to instead say,] ‘I actually had two more outings a day or spent 20 minutes outside more often than I did previously, on this treatment.’ "

None of the investigators had relevant conflicts of interest.

VANCOUVER, B.C. – Mild cognitive impairment warrants clinical attention as it confers a sharply elevated risk of death and also portends increasing social isolation, according to a pair of longitudinal studies.

Amnestic MCI Is Independent Risk Factor for Death

In the first study, investigators led by Mindy J. Katz, a senior associate in the neurology department of the Albert Einstein College of Medicine, New York, followed 733 community-dwelling participants aged 70 years or older from the Einstein Aging Study.

Susan London/IMNG Medical Media

Results showed that after confounders were taken into account, individuals with the amnestic type of mild cognitive impairment (MCI), which affects memory, were more than twice as likely to die in the next 5 years as were their cognitively intact counterparts. But those with nonamnestic MCI, which affects executive function, judgment, visuospatial ability, and/or language, were not at increased risk.

The heightened mortality with the former may be related both to its frequent progression to Alzheimer’s disease and to its impact on adherence to medical therapy for comorbidities such as hypertension and diabetes, according to Ms. Katz. "If they can’t remember to take their medications, if they don’t keep their appointments with their doctors, their medical care might not be as good as that of someone who is ... capable of keeping these appointments and taking their medications," she said in an interview at the Alzheimer’s Association International Conference 2012.

The findings apply only to people who meet diagnostic criteria for amnestic MCI, she stressed. "Just because you forget where you put your keys or you can’t remember why you walked into a room, that’s not a reason to panic." However, "after you’ve been clinically evaluated and the clinician feels that you really do have a true memory impairment, then it’s a warning sign for both the individual to prepare for the future and for caretakers to be aware that maybe this person might need more care or a plan for care in the future, and to make provisions both financially and in terms of caretaking that might be involved going forward for that individual."

Susan London/IMNG Medical Media

Senior author Dr. Richard B. Lipton, also of the Albert Einstein College of Medicine, noted that there has been some question as to whether MCI is an important entity. "Well, if it’s associated with an increased risk of death, then presumably it’s important, because death is the ultimate hard end point that is face-valid to all parties," he said.

Identifying MCI is now key for two reasons, according to Dr. Lipton. "Ultimately ... that will be a group that’s treated to keep them from progressing and developing full-blown Alzheimer’s disease. But even today, it’s important because adherence to medical therapy for people with memory impairment requires planning and family support."

In the study, 10% of participants had amnestic MCI and 9% had nonamnestic MCI at baseline. Additionally, 3% developed dementia at some time after their first evaluation.

During follow-up, nearly a third of study participants died. In a multivariate analysis, those with amnestic MCI had a significantly elevated risk of death relative to their cognitively intact peers (hazard ratio, 2.17). The other significant independent risk factors were dementia (3.26), advancing age (1.10), Geriatric Depression Scale score (1.09), and comorbidity index (1.34).

In contrast, nonamnestic MCI did not significantly affect risk, nor did educational attainment. APOE e4 allele status showed a trend toward increased mortality.

Withdrawal From Community Life

In the second study, a team led by Dr. Jeffrey Kaye of Oregon Health and Science University in Portland followed 140 community-dwelling, nondepressed older adults from the Intelligent Systems for Assessing Aging Change (ISAAC) cohort who had a mean age of 84 years at baseline.

Susan London/IMNG Medical Media

The investigators used new technology called pervasive computing or embedded ambient sensing, outfitting the participants’ homes with motion sensors and with contact sensors on doors to detect 24/7 activity patterns, including travel outside the home.

At baseline, the 20% of participants who had MCI were statistically indistinguishable from their cognitively intact counterparts in terms of the amount of time spent outside the home each day, with both averaging about 4.2 hours daily.

However, during a follow-up period of more than 3 years, there was a steady decline in this measure in the adults with MCI, compared with little change in the cognitively intact participants. In the last month of monitoring, the participants with MCI left their home for 2.9 hours daily on average, which was significantly shorter than the 3.8 hours recorded for cognitively intact participants.

"With progression of MCI, there is increasingly less time spent outside the home, and it’s independent of mood or health status, so it’s not simply because they are depressed or they are sicker," Dr. Kaye noted in an interview at the conference. "It seems to be more intrinsically a part of having MCI. This to us suggests that there is a progressive narrowing of opportunity to interact with the outside world."

The community withdrawal seen in the MCI group might occur for several reasons. "One of the highest suspicions is that as you develop increasing difficulty with your memory and thinking, you become less confident and more apprehensive about interacting with other people," he proposed. "There may also be just the practical forgetting of appointments and just not attending to things that they would usually be doing. So they are just not remembering to remember."

The participants with MCI were unaware of the change in their activity, according to Dr. Kaye. "We asked them on an annual basis about their activities, and this is very subtle. They don’t actually see this, at least using a sort of subjectively reported series of questions that were asked about their participation in clubs, classes, and social events, and going out to eat, things like that."

By enabling more accurate assessment of time spent outside the home, the technology used could have implications for both clinical care and research.

"For those of us interested in trying to get more real-time measurement of activity and behavior, we think that this kind of measure can be used to unobtrusively assess very early activity changes that may be indicative of evolving MCI," he explained. "It would be much more meaningful, rather than saying, ‘I remembered one more animal on that memory test’ [to instead say,] ‘I actually had two more outings a day or spent 20 minutes outside more often than I did previously, on this treatment.’ "

None of the investigators had relevant conflicts of interest.

VANCOUVER, B.C. – Mild cognitive impairment warrants clinical attention as it confers a sharply elevated risk of death and also portends increasing social isolation, according to a pair of longitudinal studies.

Amnestic MCI Is Independent Risk Factor for Death

In the first study, investigators led by Mindy J. Katz, a senior associate in the neurology department of the Albert Einstein College of Medicine, New York, followed 733 community-dwelling participants aged 70 years or older from the Einstein Aging Study.

Susan London/IMNG Medical Media

Results showed that after confounders were taken into account, individuals with the amnestic type of mild cognitive impairment (MCI), which affects memory, were more than twice as likely to die in the next 5 years as were their cognitively intact counterparts. But those with nonamnestic MCI, which affects executive function, judgment, visuospatial ability, and/or language, were not at increased risk.

The heightened mortality with the former may be related both to its frequent progression to Alzheimer’s disease and to its impact on adherence to medical therapy for comorbidities such as hypertension and diabetes, according to Ms. Katz. "If they can’t remember to take their medications, if they don’t keep their appointments with their doctors, their medical care might not be as good as that of someone who is ... capable of keeping these appointments and taking their medications," she said in an interview at the Alzheimer’s Association International Conference 2012.

The findings apply only to people who meet diagnostic criteria for amnestic MCI, she stressed. "Just because you forget where you put your keys or you can’t remember why you walked into a room, that’s not a reason to panic." However, "after you’ve been clinically evaluated and the clinician feels that you really do have a true memory impairment, then it’s a warning sign for both the individual to prepare for the future and for caretakers to be aware that maybe this person might need more care or a plan for care in the future, and to make provisions both financially and in terms of caretaking that might be involved going forward for that individual."

Susan London/IMNG Medical Media

Senior author Dr. Richard B. Lipton, also of the Albert Einstein College of Medicine, noted that there has been some question as to whether MCI is an important entity. "Well, if it’s associated with an increased risk of death, then presumably it’s important, because death is the ultimate hard end point that is face-valid to all parties," he said.

Identifying MCI is now key for two reasons, according to Dr. Lipton. "Ultimately ... that will be a group that’s treated to keep them from progressing and developing full-blown Alzheimer’s disease. But even today, it’s important because adherence to medical therapy for people with memory impairment requires planning and family support."

In the study, 10% of participants had amnestic MCI and 9% had nonamnestic MCI at baseline. Additionally, 3% developed dementia at some time after their first evaluation.

During follow-up, nearly a third of study participants died. In a multivariate analysis, those with amnestic MCI had a significantly elevated risk of death relative to their cognitively intact peers (hazard ratio, 2.17). The other significant independent risk factors were dementia (3.26), advancing age (1.10), Geriatric Depression Scale score (1.09), and comorbidity index (1.34).

In contrast, nonamnestic MCI did not significantly affect risk, nor did educational attainment. APOE e4 allele status showed a trend toward increased mortality.

Withdrawal From Community Life

In the second study, a team led by Dr. Jeffrey Kaye of Oregon Health and Science University in Portland followed 140 community-dwelling, nondepressed older adults from the Intelligent Systems for Assessing Aging Change (ISAAC) cohort who had a mean age of 84 years at baseline.

Susan London/IMNG Medical Media

The investigators used new technology called pervasive computing or embedded ambient sensing, outfitting the participants’ homes with motion sensors and with contact sensors on doors to detect 24/7 activity patterns, including travel outside the home.

At baseline, the 20% of participants who had MCI were statistically indistinguishable from their cognitively intact counterparts in terms of the amount of time spent outside the home each day, with both averaging about 4.2 hours daily.

However, during a follow-up period of more than 3 years, there was a steady decline in this measure in the adults with MCI, compared with little change in the cognitively intact participants. In the last month of monitoring, the participants with MCI left their home for 2.9 hours daily on average, which was significantly shorter than the 3.8 hours recorded for cognitively intact participants.

"With progression of MCI, there is increasingly less time spent outside the home, and it’s independent of mood or health status, so it’s not simply because they are depressed or they are sicker," Dr. Kaye noted in an interview at the conference. "It seems to be more intrinsically a part of having MCI. This to us suggests that there is a progressive narrowing of opportunity to interact with the outside world."

The community withdrawal seen in the MCI group might occur for several reasons. "One of the highest suspicions is that as you develop increasing difficulty with your memory and thinking, you become less confident and more apprehensive about interacting with other people," he proposed. "There may also be just the practical forgetting of appointments and just not attending to things that they would usually be doing. So they are just not remembering to remember."

The participants with MCI were unaware of the change in their activity, according to Dr. Kaye. "We asked them on an annual basis about their activities, and this is very subtle. They don’t actually see this, at least using a sort of subjectively reported series of questions that were asked about their participation in clubs, classes, and social events, and going out to eat, things like that."

By enabling more accurate assessment of time spent outside the home, the technology used could have implications for both clinical care and research.

"For those of us interested in trying to get more real-time measurement of activity and behavior, we think that this kind of measure can be used to unobtrusively assess very early activity changes that may be indicative of evolving MCI," he explained. "It would be much more meaningful, rather than saying, ‘I remembered one more animal on that memory test’ [to instead say,] ‘I actually had two more outings a day or spent 20 minutes outside more often than I did previously, on this treatment.’ "

None of the investigators had relevant conflicts of interest.

Neurologists Dr. Richard Caselli and Dr. Marwan Sabbagh discuss the direction of Alzheimer’s disease research and some of the hot topics at the 2012 Alzheimer’s Association International Conference in Vancouver, B.C.

Some of the latest developments under discussion at the conference include presymptomatic clinical trials involving individuals at high risk for Alzheimer’s, the value of amyloid PET imaging techniques, and exploiting the discovery of a protective mutation against Alzheimer’s with beta-secretase inhibitors.

Neurologists Dr. Richard Caselli and Dr. Marwan Sabbagh discuss the direction of Alzheimer’s disease research and some of the hot topics at the 2012 Alzheimer’s Association International Conference in Vancouver, B.C.

Some of the latest developments under discussion at the conference include presymptomatic clinical trials involving individuals at high risk for Alzheimer’s, the value of amyloid PET imaging techniques, and exploiting the discovery of a protective mutation against Alzheimer’s with beta-secretase inhibitors.

Neurologists Dr. Richard Caselli and Dr. Marwan Sabbagh discuss the direction of Alzheimer’s disease research and some of the hot topics at the 2012 Alzheimer’s Association International Conference in Vancouver, B.C.

Some of the latest developments under discussion at the conference include presymptomatic clinical trials involving individuals at high risk for Alzheimer’s, the value of amyloid PET imaging techniques, and exploiting the discovery of a protective mutation against Alzheimer’s with beta-secretase inhibitors.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

VANCOUVER, B.C. – Disordered sleep in mid- to late life is associated with an increased risk for future cognitive impairment and may alter the dynamics of the Alzheimer’s disease–associated protein amyloid-beta, according to several studies.

It’s important that physicians recognize disordered sleep as a modifiable risk factor, Dr. Kristine Yaffe said in an interview.

"Please attend to sleep hygiene in your elderly patients," said Dr. Yaffe, director of the memory disorders clinic at the San Francisco VA Medical Center. "Some people think that 50% of elderly people have some kind of sleep complaint. They are common and they are treatable."

Dr. Yaffe and her colleagues studied 1,309 elderly women who completed several days of sleep observation as part of a 15-year longitudinal study. They measured the motor activity of the women (mean age, 82 years) during sleep via wrist actigraphy. All of the participants had several neuropsychological evaluations and cognitive measurements during the study. A subset of 298 patients also underwent polysomnography.

After 5 years, women with sleep-disordered breathing were twice as likely to develop mild cognitive impairment or dementia as were those who slept normally. There was a similar risk level for women who had delayed sleep acrophase – difficulty falling asleep before the early morning hours and trouble waking up before late morning or early afternoon.

Women with greater nighttime wakefulness were more than twice as likely to show impaired global cognitive functioning, and twice as likely to have delayed verbal recall.

"We already know that sleep deprivation and abnormal sleep patterns are associated with falls and increased morbidity and mortality," said Dr. Yaffe, who also is a professor in the departments of psychiatry, neurology, epidemiology, and biostatistics at the University of California, San Francisco. "This is the first study showing that disordered sleep is a risk factor for later cognitive problems.

"It’s important for clinicians to check for sleep problems and excessive daytime sleepiness as a possibly treatable cause of later cognitive problems," she said at the Alzheimer’s Disease International Conference 2012. "Sleep habits are as important in prevention of dementia as diabetes and obesity."

Elizabeth Devore, Sc.D., of Brigham and Women’s Hospital, Boston, found similar results in her analysis of sleep data extracted from the longitudinal Nurses’ Health Study. The sleep study included information on 15,263 women, who were aged 70 or older at the time of their first cognitive evaluation. These subjects were followed for 6 years with cognitive testing every other year.

The women reported their sleep duration and quality at ages 40-65 and at ages 54-79. A normal night’s sleep was considered to be 7 hours.

When comparing sleep duration to later cognitive status, Dr. Devore found that:

• Those who slept 5 hours per day or less had lower average cognition than those who slept 7 hours per day.

• Those who slept 9 hours per day or more also had lower average cognition than those who slept 7 hours per day.

• Too little or too much sleep was cognitively equivalent to 2 years of aging.

When the researchers evaluated the effects of change in sleep duration from mid- to later life, they observed that women whose sleep changed by 2 hours per day or more had worse cognitive function than those with no change in sleep duration, independent of their initial sleep duration.

"Either too little or too much sleep, and sleep duration changes over time, might contribute to cognitive decline in older adults," she said. "This is up-and-coming research and has great implications for public health. We need to do more research in this area, especially looking at sleep duration over the course of life. It’s simple, and down the road it could lead to the development of sleep and circadian rhythm strategies to target therapy."

Dr. Devore also found that shortened or extended sleep patterns were also entwined with abnormalities in the processing of amyloid-beta (Abeta) peptides, which are believed to cause neuronal dysfunction in Alzheimer’s disease. Subjects with these extremes of sleep duration showed a skewed proportion of Abeta-40 and Abeta-42 peptides in cerebrospinal fluid, suggesting that more amyloid could be accruing in brain plaques.

Dr. Yafei Huang and her associates at Washington University, St. Louis, also found that the circadian pattern of Abeta secretion is altered in Alzheimer’s disease. Her study involved three groups: 12 Alzheimer’s patients with a mean age of 72 years, 8 age-matched controls, and 10 young, healthy controls with a mean age of 36 years.

Each subject underwent hourly sampling of cerebrospinal fluid (CSF) and plasma for 36 hours during waking and sleep times. Dr. Huang plotted the circadian secretion patterns of Abeta-40 and Abeta-42, and the amyloid precursor protein (APP).

While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.

Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.

"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.

This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.

Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.

"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."

Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.

VANCOUVER, B.C.  – An online community-wide healthy aging program has increased cognitive screening in physicians’ offices by 50% in 18 months, targeting the population so well that half of participants show cognitive impairment when clinically evaluated.

Since the Orange County (Calif.) Vital Aging Program debuted in September 2010, it has linked more than 6,000 residents to physicians for cognitive assessments – an average of 400 evaluations per month, Dr. William Shankle said at the Alzheimer’s Association International Conference 2012.

Photo Michele G. Sullivan /IMNG Medical Media

“Many people with cognitive impairment or early dementia are not seeing a physician, and for various reasons,” said Dr. Shankle, director of the memory and cognitive disorders unit at Hoag Neurosciences Institute in Newport Beach, Calif. “Most don’t think cognitive impairment is treatable, and most associate memory loss with Alzheimer’s disease.”

That association provokes a deep fear, putting many in a state of denial and dampening their desire to reach out to physicians. The ability to self-screen online with a survey based on clinically validated questions can ease that fear – about half of those who take the survey discover that their memory problems are simply the result of normal aging. For the other half, the self-assessment suggests that a formal evaluation can get them the help they need to deal proactively with a cognitive problem, Dr. Shankle said.

If a screen comes back positive, residents can search the Vital Aging website for a physician close to them who has the special training to help. The program also reaches out to the greater community of those without memory concerns. Visitors can explore educational links, sign up for a monthly newsletter, and find out about public lectures focusing on brain health and lifestyle changes that can optimize it.

In fact, a preliminary assessment shows that people who take the memory evaluation, attend a lecture, and then follow through with the suggested changes perform better on memory tests at a follow-up assessment 1 year later.

“We’ve seen that 75% of people who attend these lectures do go back to their doctors for a 1-year follow-up visit, which is great,” Dr. Shankle said. “Participants are very willing to educate themselves, make these positive lifestyle changes, and manage the risk factors that can influence their cognitive health.” For physicians, the program provides a portal to specially focused continuing medical education, he said. “These CME activities are differentiated to dig down to the individual physician’s level of knowledge and start there, or to provide more advanced training to those who already have knowledge of the issues.”

Community programs like these are one way to help manage the money pit that is dementia care. “Dementia costs a lot of money. On average, Medicare pays three times more per year to care for a dementia patient than a patient who doesn’t have it.

This creates an urgent need to address cognitive health care in a community – or this will bankrupt medical care. We have a system that is broken. This is one way to begin to fix it,” he said. Dr. Shankle disclosed that he is an employee of and holds stock in Medical Care Corp., which supplied some of the technology used in the Orange County Vital Aging Project.

VANCOUVER, B.C.  – An online community-wide healthy aging program has increased cognitive screening in physicians’ offices by 50% in 18 months, targeting the population so well that half of participants show cognitive impairment when clinically evaluated.

Since the Orange County (Calif.) Vital Aging Program debuted in September 2010, it has linked more than 6,000 residents to physicians for cognitive assessments – an average of 400 evaluations per month, Dr. William Shankle said at the Alzheimer’s Association International Conference 2012.

Photo Michele G. Sullivan /IMNG Medical Media

“Many people with cognitive impairment or early dementia are not seeing a physician, and for various reasons,” said Dr. Shankle, director of the memory and cognitive disorders unit at Hoag Neurosciences Institute in Newport Beach, Calif. “Most don’t think cognitive impairment is treatable, and most associate memory loss with Alzheimer’s disease.”

That association provokes a deep fear, putting many in a state of denial and dampening their desire to reach out to physicians. The ability to self-screen online with a survey based on clinically validated questions can ease that fear – about half of those who take the survey discover that their memory problems are simply the result of normal aging. For the other half, the self-assessment suggests that a formal evaluation can get them the help they need to deal proactively with a cognitive problem, Dr. Shankle said.

If a screen comes back positive, residents can search the Vital Aging website for a physician close to them who has the special training to help. The program also reaches out to the greater community of those without memory concerns. Visitors can explore educational links, sign up for a monthly newsletter, and find out about public lectures focusing on brain health and lifestyle changes that can optimize it.

In fact, a preliminary assessment shows that people who take the memory evaluation, attend a lecture, and then follow through with the suggested changes perform better on memory tests at a follow-up assessment 1 year later.

“We’ve seen that 75% of people who attend these lectures do go back to their doctors for a 1-year follow-up visit, which is great,” Dr. Shankle said. “Participants are very willing to educate themselves, make these positive lifestyle changes, and manage the risk factors that can influence their cognitive health.” For physicians, the program provides a portal to specially focused continuing medical education, he said. “These CME activities are differentiated to dig down to the individual physician’s level of knowledge and start there, or to provide more advanced training to those who already have knowledge of the issues.”

Community programs like these are one way to help manage the money pit that is dementia care. “Dementia costs a lot of money. On average, Medicare pays three times more per year to care for a dementia patient than a patient who doesn’t have it.

This creates an urgent need to address cognitive health care in a community – or this will bankrupt medical care. We have a system that is broken. This is one way to begin to fix it,” he said. Dr. Shankle disclosed that he is an employee of and holds stock in Medical Care Corp., which supplied some of the technology used in the Orange County Vital Aging Project.

VANCOUVER, B.C.  – An online community-wide healthy aging program has increased cognitive screening in physicians’ offices by 50% in 18 months, targeting the population so well that half of participants show cognitive impairment when clinically evaluated.

Since the Orange County (Calif.) Vital Aging Program debuted in September 2010, it has linked more than 6,000 residents to physicians for cognitive assessments – an average of 400 evaluations per month, Dr. William Shankle said at the Alzheimer’s Association International Conference 2012.

Photo Michele G. Sullivan /IMNG Medical Media

“Many people with cognitive impairment or early dementia are not seeing a physician, and for various reasons,” said Dr. Shankle, director of the memory and cognitive disorders unit at Hoag Neurosciences Institute in Newport Beach, Calif. “Most don’t think cognitive impairment is treatable, and most associate memory loss with Alzheimer’s disease.”

That association provokes a deep fear, putting many in a state of denial and dampening their desire to reach out to physicians. The ability to self-screen online with a survey based on clinically validated questions can ease that fear – about half of those who take the survey discover that their memory problems are simply the result of normal aging. For the other half, the self-assessment suggests that a formal evaluation can get them the help they need to deal proactively with a cognitive problem, Dr. Shankle said.

If a screen comes back positive, residents can search the Vital Aging website for a physician close to them who has the special training to help. The program also reaches out to the greater community of those without memory concerns. Visitors can explore educational links, sign up for a monthly newsletter, and find out about public lectures focusing on brain health and lifestyle changes that can optimize it.

In fact, a preliminary assessment shows that people who take the memory evaluation, attend a lecture, and then follow through with the suggested changes perform better on memory tests at a follow-up assessment 1 year later.

“We’ve seen that 75% of people who attend these lectures do go back to their doctors for a 1-year follow-up visit, which is great,” Dr. Shankle said. “Participants are very willing to educate themselves, make these positive lifestyle changes, and manage the risk factors that can influence their cognitive health.” For physicians, the program provides a portal to specially focused continuing medical education, he said. “These CME activities are differentiated to dig down to the individual physician’s level of knowledge and start there, or to provide more advanced training to those who already have knowledge of the issues.”

Community programs like these are one way to help manage the money pit that is dementia care. “Dementia costs a lot of money. On average, Medicare pays three times more per year to care for a dementia patient than a patient who doesn’t have it.

This creates an urgent need to address cognitive health care in a community – or this will bankrupt medical care. We have a system that is broken. This is one way to begin to fix it,” he said. Dr. Shankle disclosed that he is an employee of and holds stock in Medical Care Corp., which supplied some of the technology used in the Orange County Vital Aging Project.

VANCOUVER, B.C. – Physical activity improves not only the heart and lungs, but the brain as well, providing a triad of benefits: improved cognition, better physiologic functioning, and increased brain volume and hints of revved-up neuronal growth.

Studies presented July 15 at the Alzheimer’s Association International Conference 2012 agreed: Getting active is essential for preserving cognitive health.

Exactly how exercise boosts brain function is still a matter of debate, Teresa Liu-Ambrose, Ph.D., said in an interview.

"In addition to getting the physical benefits of exercise, people are also getting social interaction and mental stimulation," said Dr. Liu-Ambrose, director of the Aging, Mobility, and Cognitive Neuroscience Lab at the University of British Columbia, Vancouver. Group activities, like exercise, can also help unwind the tangle of diminished executive function and social isolation, a damaging pair.

"When executive function begins to deteriorate, people know that they are losing some of their ability to interact, and so they withdraw and become isolated," she said. The lack of social interaction contributes to the downward slide of cognition.

Dr. Liu-Ambrose was the primary investigator of a randomized controlled trial that examined the benefits of three different exercise regimens, each conducted twice a week for 6 months: resistance training; aerobic training; and balance and tone training, which served as the comparator group.

The subjects were 86 women aged 70-80 years. They all still lived at home, but had probable mild cognitive impairment. The group is an important one because the natural history of Alzheimer’s disease suggests that about half of those who develop mild cognitive impairment will go on to develop Alzheimer’s dementia.

All of the programs were progressive, she said. Those in the weight program started with the largest weights they could handle with good form, which were increased as soon as the women exceeded the required number of repetitions. The aerobic group increased their walking speed based on heart rate and perceived exertion. The control group loaded their exercises as well, increasing repetitions and stretching as the trial progressed.

After 6 months, the strength training group had improved by 17% over baseline on measures of executive function, which was significantly better than either of the other groups. These women also experienced significant gains in associative memory.

Dr. Liu-Ambrose also saw physiologic correlates to the cognitive findings. Functional MRI showed improved blood flow in three brain regions involved with encoding and memorization of nonverbal associations: the right lingual gyrus, the occipital fusiform gyrus, and the right frontal pole.

The aerobic training group improved in balance, mobility, and cardiovascular capacity, but did not have the same kind of cognitive or brain physiologic gains, she added. The balance and tone group maintained their cognitive ability without any additional decline, but didn’t experience any additional benefit either.

"I want to stress that we were seeing a real improvement with resistance training – not just maintenance like we did in the control group. We’re talking about women who already have some level of cognitive impairment. The most positive way of looking at this is that exercise could be a magic bullet. There is evidence now that exercise may not only be preventive – but a potential treatment."

In a separate study, Kirk Erickson, Ph.D., presented evidence of the molecular underpinning of exercise-induced brain volume changes: Physical activity, he said, stimulates the release of molecules that promote neuronal growth.

Dr. Erickson, a cognitive neuroscience researcher at the University of Pittsburgh, described the results of a walking program that involved 120 cognitively healthy, elderly adults.

The participants had been sedentary for at least the previous 6 months. They were randomized either to a 1-year program of moderately intense walking or to a 1-year stretching and toning group. At baseline and at 1 year, Dr. Erickson and his colleagues measured brain volume and levels of brain-derived neurotrophic factor (BDNF).

BDNF is a protein that affects neurons in several ways: It supports healthy neuronal function, encourages stem cells to differentiate into neurons, and stimulates dendritic expansion. BDNF is particularly active in regions associated with memory and executive functioning.

At the study’s end, Dr. Erickson and his associates found that those in the walking program had about a 2% increase in the size of the anterior hippocampus, compared with the stretching and toning group. Increases in BDNF positively correlated with the volume change. He also saw increases in the volume of the prefrontal cortex, which correlated with increased cardiorespiratory fitness.

Just how to translate these controlled experimental situations into effective, real-life practice isn’t completely clear, Dr. Liu-Ambrose said, especially when patients already have difficulty with planning and prioritization.

Her colleague, Nader Fallah, Ph.D., also of the University of British Columbia, used his expertise in biostatistics to explore that problem. Using a similar cohort of women, he found that those with higher baseline cognitive function reaped the greatest benefit from resistance training.

Dr. Fallah conducted a secondary analysis of a 12-month, randomized, controlled trial of 155 women aged 65-75 years (Neurobiol. Aging 2012;33:1690-8). The women were assigned to resistance training or balance and tone training.

This new analysis found that women with lower baseline functioning not only experienced less improvement from exercise, but also responded equally to both resistance training and balance and tone training.

"To our knowledge, this is the first study to demonstrate that an individual’s baseline self-regulatory capacity impacts the amount of cognitive benefit the person will reap from targeted exercise training," Dr. Fallah said in a written statement.

Dr. Liu-Ambrose said the study sheds valuable light on the concept of personalizing exercise prescriptions.

"I think this brings us another dimension to consider," Dr. Liu-Ambrose said. "When we prescribe exercise, most of the time we focus on physical ability: ‘Can the knees take it, what is the cardiovascular state?’ But people who have better executive function at baseline can execute this prescription better. They can plan their time, prioritize their activities, and follow through with the commitment."

Dr. Fallah’s findings suggest that "cognitive priming" might improve outcomes in prescribed exercise. Computerized brain training games are one thing to consider. They’ve been shown to improve memory and executive function for both cognitively healthy and impaired older adults. Just a small improvement in executive function and memory could be enough to get a patient invested in an exercise program.

"But for those with more pronounced dementia, it’s really about engaging the caregiver," Dr. Liu-Ambrose concluded. "We need to give them the tools they need to implement this as part of the daily lives of their loved ones."

None of the researchers reported having any financial conflicts of interest.

VANCOUVER, B.C. – Physical activity improves not only the heart and lungs, but the brain as well, providing a triad of benefits: improved cognition, better physiologic functioning, and increased brain volume and hints of revved-up neuronal growth.

Studies presented July 15 at the Alzheimer’s Association International Conference 2012 agreed: Getting active is essential for preserving cognitive health.

Exactly how exercise boosts brain function is still a matter of debate, Teresa Liu-Ambrose, Ph.D., said in an interview.

"In addition to getting the physical benefits of exercise, people are also getting social interaction and mental stimulation," said Dr. Liu-Ambrose, director of the Aging, Mobility, and Cognitive Neuroscience Lab at the University of British Columbia, Vancouver. Group activities, like exercise, can also help unwind the tangle of diminished executive function and social isolation, a damaging pair.

"When executive function begins to deteriorate, people know that they are losing some of their ability to interact, and so they withdraw and become isolated," she said. The lack of social interaction contributes to the downward slide of cognition.

Dr. Liu-Ambrose was the primary investigator of a randomized controlled trial that examined the benefits of three different exercise regimens, each conducted twice a week for 6 months: resistance training; aerobic training; and balance and tone training, which served as the comparator group.

The subjects were 86 women aged 70-80 years. They all still lived at home, but had probable mild cognitive impairment. The group is an important one because the natural history of Alzheimer’s disease suggests that about half of those who develop mild cognitive impairment will go on to develop Alzheimer’s dementia.

All of the programs were progressive, she said. Those in the weight program started with the largest weights they could handle with good form, which were increased as soon as the women exceeded the required number of repetitions. The aerobic group increased their walking speed based on heart rate and perceived exertion. The control group loaded their exercises as well, increasing repetitions and stretching as the trial progressed.

After 6 months, the strength training group had improved by 17% over baseline on measures of executive function, which was significantly better than either of the other groups. These women also experienced significant gains in associative memory.

Dr. Liu-Ambrose also saw physiologic correlates to the cognitive findings. Functional MRI showed improved blood flow in three brain regions involved with encoding and memorization of nonverbal associations: the right lingual gyrus, the occipital fusiform gyrus, and the right frontal pole.

The aerobic training group improved in balance, mobility, and cardiovascular capacity, but did not have the same kind of cognitive or brain physiologic gains, she added. The balance and tone group maintained their cognitive ability without any additional decline, but didn’t experience any additional benefit either.

"I want to stress that we were seeing a real improvement with resistance training – not just maintenance like we did in the control group. We’re talking about women who already have some level of cognitive impairment. The most positive way of looking at this is that exercise could be a magic bullet. There is evidence now that exercise may not only be preventive – but a potential treatment."

In a separate study, Kirk Erickson, Ph.D., presented evidence of the molecular underpinning of exercise-induced brain volume changes: Physical activity, he said, stimulates the release of molecules that promote neuronal growth.

Dr. Erickson, a cognitive neuroscience researcher at the University of Pittsburgh, described the results of a walking program that involved 120 cognitively healthy, elderly adults.

The participants had been sedentary for at least the previous 6 months. They were randomized either to a 1-year program of moderately intense walking or to a 1-year stretching and toning group. At baseline and at 1 year, Dr. Erickson and his colleagues measured brain volume and levels of brain-derived neurotrophic factor (BDNF).

BDNF is a protein that affects neurons in several ways: It supports healthy neuronal function, encourages stem cells to differentiate into neurons, and stimulates dendritic expansion. BDNF is particularly active in regions associated with memory and executive functioning.

At the study’s end, Dr. Erickson and his associates found that those in the walking program had about a 2% increase in the size of the anterior hippocampus, compared with the stretching and toning group. Increases in BDNF positively correlated with the volume change. He also saw increases in the volume of the prefrontal cortex, which correlated with increased cardiorespiratory fitness.

Just how to translate these controlled experimental situations into effective, real-life practice isn’t completely clear, Dr. Liu-Ambrose said, especially when patients already have difficulty with planning and prioritization.

Her colleague, Nader Fallah, Ph.D., also of the University of British Columbia, used his expertise in biostatistics to explore that problem. Using a similar cohort of women, he found that those with higher baseline cognitive function reaped the greatest benefit from resistance training.

Dr. Fallah conducted a secondary analysis of a 12-month, randomized, controlled trial of 155 women aged 65-75 years (Neurobiol. Aging 2012;33:1690-8). The women were assigned to resistance training or balance and tone training.

This new analysis found that women with lower baseline functioning not only experienced less improvement from exercise, but also responded equally to both resistance training and balance and tone training.

"To our knowledge, this is the first study to demonstrate that an individual’s baseline self-regulatory capacity impacts the amount of cognitive benefit the person will reap from targeted exercise training," Dr. Fallah said in a written statement.

Dr. Liu-Ambrose said the study sheds valuable light on the concept of personalizing exercise prescriptions.

"I think this brings us another dimension to consider," Dr. Liu-Ambrose said. "When we prescribe exercise, most of the time we focus on physical ability: ‘Can the knees take it, what is the cardiovascular state?’ But people who have better executive function at baseline can execute this prescription better. They can plan their time, prioritize their activities, and follow through with the commitment."

Dr. Fallah’s findings suggest that "cognitive priming" might improve outcomes in prescribed exercise. Computerized brain training games are one thing to consider. They’ve been shown to improve memory and executive function for both cognitively healthy and impaired older adults. Just a small improvement in executive function and memory could be enough to get a patient invested in an exercise program.

"But for those with more pronounced dementia, it’s really about engaging the caregiver," Dr. Liu-Ambrose concluded. "We need to give them the tools they need to implement this as part of the daily lives of their loved ones."

None of the researchers reported having any financial conflicts of interest.

VANCOUVER, B.C. – Physical activity improves not only the heart and lungs, but the brain as well, providing a triad of benefits: improved cognition, better physiologic functioning, and increased brain volume and hints of revved-up neuronal growth.

Studies presented July 15 at the Alzheimer’s Association International Conference 2012 agreed: Getting active is essential for preserving cognitive health.

Exactly how exercise boosts brain function is still a matter of debate, Teresa Liu-Ambrose, Ph.D., said in an interview.

"In addition to getting the physical benefits of exercise, people are also getting social interaction and mental stimulation," said Dr. Liu-Ambrose, director of the Aging, Mobility, and Cognitive Neuroscience Lab at the University of British Columbia, Vancouver. Group activities, like exercise, can also help unwind the tangle of diminished executive function and social isolation, a damaging pair.

"When executive function begins to deteriorate, people know that they are losing some of their ability to interact, and so they withdraw and become isolated," she said. The lack of social interaction contributes to the downward slide of cognition.

Dr. Liu-Ambrose was the primary investigator of a randomized controlled trial that examined the benefits of three different exercise regimens, each conducted twice a week for 6 months: resistance training; aerobic training; and balance and tone training, which served as the comparator group.

The subjects were 86 women aged 70-80 years. They all still lived at home, but had probable mild cognitive impairment. The group is an important one because the natural history of Alzheimer’s disease suggests that about half of those who develop mild cognitive impairment will go on to develop Alzheimer’s dementia.

All of the programs were progressive, she said. Those in the weight program started with the largest weights they could handle with good form, which were increased as soon as the women exceeded the required number of repetitions. The aerobic group increased their walking speed based on heart rate and perceived exertion. The control group loaded their exercises as well, increasing repetitions and stretching as the trial progressed.

After 6 months, the strength training group had improved by 17% over baseline on measures of executive function, which was significantly better than either of the other groups. These women also experienced significant gains in associative memory.

Dr. Liu-Ambrose also saw physiologic correlates to the cognitive findings. Functional MRI showed improved blood flow in three brain regions involved with encoding and memorization of nonverbal associations: the right lingual gyrus, the occipital fusiform gyrus, and the right frontal pole.

The aerobic training group improved in balance, mobility, and cardiovascular capacity, but did not have the same kind of cognitive or brain physiologic gains, she added. The balance and tone group maintained their cognitive ability without any additional decline, but didn’t experience any additional benefit either.

"I want to stress that we were seeing a real improvement with resistance training – not just maintenance like we did in the control group. We’re talking about women who already have some level of cognitive impairment. The most positive way of looking at this is that exercise could be a magic bullet. There is evidence now that exercise may not only be preventive – but a potential treatment."

In a separate study, Kirk Erickson, Ph.D., presented evidence of the molecular underpinning of exercise-induced brain volume changes: Physical activity, he said, stimulates the release of molecules that promote neuronal growth.

Dr. Erickson, a cognitive neuroscience researcher at the University of Pittsburgh, described the results of a walking program that involved 120 cognitively healthy, elderly adults.

The participants had been sedentary for at least the previous 6 months. They were randomized either to a 1-year program of moderately intense walking or to a 1-year stretching and toning group. At baseline and at 1 year, Dr. Erickson and his colleagues measured brain volume and levels of brain-derived neurotrophic factor (BDNF).

BDNF is a protein that affects neurons in several ways: It supports healthy neuronal function, encourages stem cells to differentiate into neurons, and stimulates dendritic expansion. BDNF is particularly active in regions associated with memory and executive functioning.

At the study’s end, Dr. Erickson and his associates found that those in the walking program had about a 2% increase in the size of the anterior hippocampus, compared with the stretching and toning group. Increases in BDNF positively correlated with the volume change. He also saw increases in the volume of the prefrontal cortex, which correlated with increased cardiorespiratory fitness.

Just how to translate these controlled experimental situations into effective, real-life practice isn’t completely clear, Dr. Liu-Ambrose said, especially when patients already have difficulty with planning and prioritization.

Her colleague, Nader Fallah, Ph.D., also of the University of British Columbia, used his expertise in biostatistics to explore that problem. Using a similar cohort of women, he found that those with higher baseline cognitive function reaped the greatest benefit from resistance training.

Dr. Fallah conducted a secondary analysis of a 12-month, randomized, controlled trial of 155 women aged 65-75 years (Neurobiol. Aging 2012;33:1690-8). The women were assigned to resistance training or balance and tone training.

This new analysis found that women with lower baseline functioning not only experienced less improvement from exercise, but also responded equally to both resistance training and balance and tone training.

"To our knowledge, this is the first study to demonstrate that an individual’s baseline self-regulatory capacity impacts the amount of cognitive benefit the person will reap from targeted exercise training," Dr. Fallah said in a written statement.

Dr. Liu-Ambrose said the study sheds valuable light on the concept of personalizing exercise prescriptions.

"I think this brings us another dimension to consider," Dr. Liu-Ambrose said. "When we prescribe exercise, most of the time we focus on physical ability: ‘Can the knees take it, what is the cardiovascular state?’ But people who have better executive function at baseline can execute this prescription better. They can plan their time, prioritize their activities, and follow through with the commitment."

Dr. Fallah’s findings suggest that "cognitive priming" might improve outcomes in prescribed exercise. Computerized brain training games are one thing to consider. They’ve been shown to improve memory and executive function for both cognitively healthy and impaired older adults. Just a small improvement in executive function and memory could be enough to get a patient invested in an exercise program.

"But for those with more pronounced dementia, it’s really about engaging the caregiver," Dr. Liu-Ambrose concluded. "We need to give them the tools they need to implement this as part of the daily lives of their loved ones."

None of the researchers reported having any financial conflicts of interest.

The Alzheimer's Association International Conference of 2012 is taking place in Vancouver, B.C., on July 14-19. Our reporting team will provide on-site coverage. Check here for the latest from this important meeting.

The Alzheimer's Association International Conference of 2012 is taking place in Vancouver, B.C., on July 14-19. Our reporting team will provide on-site coverage. Check here for the latest from this important meeting.

The Alzheimer's Association International Conference of 2012 is taking place in Vancouver, B.C., on July 14-19. Our reporting team will provide on-site coverage. Check here for the latest from this important meeting.