Literature Monitor

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].