Rush Alzheimers Disease Center

Chicago, United States

Rush Alzheimers Disease Center

Chicago, United States

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Wilson R.S.,Rush Alzheimers Disease Center | Wilson R.S.,Rush University Medical Center | Begeny C.T.,Rush University Medical Center | Schneider J.A.,Rush Alzheimers Disease Center | Bennett D.A.,Rush Alzheimers Disease Center
American Journal of Geriatric Psychiatry | Year: 2011

Objective: To identify the components of the neuroticism trait most responsible for its association with cognitive decline and dementia in old age. Design: Longitudinal clinical-pathologic cohort study. Setting: Chicago metropolitan area. Participants: A total of 785 older persons without dementia completed standard self-report measures of six components of neuroticism and then had annual clinical evaluations for a mean of 3.4 years and brain autopsy in the event of death. Measurements: Incidence of clinically diagnosed Alzheimer disease (AD), change in global and specific cognitive functions, and postmortem measures of plaques and tangles, cerebral infarction, and Lewy bodies. Results: During follow-up, 94 individuals developed AD. Higher levels of anxiety and vulnerability to stress were associated with increased risk of AD and more rapid decline in global cognition, with no effects for the other four trait components. In analyses of specific cognitive systems, neuroticism subscales were related to decline in episodic memory, working memory, and perceptual speed, but not in semantic memory or visuospatial ability. No component of neuroticism was related to the neuropathologic lesions most commonly associated with late-life dementia. Conclusions: Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety and their correlation with decline in the abilityto process and retain new information. © 2011 American Association for Geriatric Psychiatry.


Wilson R.S.,Rush Alzheimers Disease Center | Leurgans S.E.,Rush Alzheimers Disease Center | Schneider J.A.,Rush Alzheimers Disease Center | Schneider J.A.,Rush University Medical Center | Bennett D.A.,Rush Alzheimers Disease Center
Neurology | Year: 2010

Objective: To assess the contribution of dementia-related neuropathologic lesions to age-related and disease-related change in cognitive function. Methods: A total of 354 Catholic nuns, priests, and brothers had annual clinical evaluations for up to 13 years, died, and underwent brain autopsy. The clinical evaluations included detailed testing of cognitive function from which previously established composite measures of global cognition and specific cognitive functions were derived. As part of a uniform neuropathologic evaluation, the density of neurofibrillary tangles was summarized in a composite measure and the presence of Lewy bodies and gross and microscopic cerebral infarction was noted. Results: During follow-up, rate of global cognitive decline was gradual at first and then more than quadrupled in the last 4 to 5 years of life consistent with the onset of progressive dementia. Neurofibrillary tangles, cerebral infarction, and neocortical Lewy bodies all contributed to gradual age-related cognitive decline and little age-related decline was evident in the absence of these lesions. Neurofibrillary tangles and neocortical Lewy bodies contributed to precipitous disease-related cognitive decline, but substantial disease-related decline was evident even in the absence of these lesions. Conclusion: Mild age-related decline in cognitive function is mainly due to the neuropathologic lesions traditionally associated with dementia. Copyright © 2010 by AAN Enterprises, Inc. All rights reserved.


James B.D.,Rush Alzheimers Disease Center | Leurgans S.E.,Rush Alzheimers Disease Center | Leurgans S.E.,Rush University Medical Center | Hebert L.E.,Rush University Medical Center | And 5 more authors.
Neurology | Year: 2014

Objective: To assess the burden of mortality attributable to Alzheimer disease (AD) dementia in the United States. Methods: Data came from 2,566 persons aged 65 years and older (mean 78.1 years)without dementia at baseline from 2 cohort studies of aging with identical annual diagnostic assessments of dementia. Because both studies require organ donation, ascertainment of mortality was complete and dates of death accurate. Mortality hazard ratios (HRs) after incident AD dementia were estimated per 10-year age strata from proportional hazardsmodels. Population attributable risk percentage was derived to estimate excess mortality after a diagnosis of AD dementia. The number of excess deaths attributable to AD dementia in the United States was then estimated. Results: Over an average of 8 years, 559 participants (21.8%) without dementia at baseline developed AD dementia and 1,090 (42.4%) died. Median time from AD dementia diagnosis to death was 3.8 years. The mortality HR for AD dementia was 4.30 (confidence interval 5 3.33, 5.58) for ages 75-84 years and 2.77 (confidence interval 5 2.37, 3.23) for ages 85 years and older (too few deaths after AD dementia in ages 65-74 were available to estimate HR). Population attributable risk percentage was 37.0% for ages 75-84 and 35.8%for ages 85 and older. An estimated 503,400 deaths in Americans aged 75 years and older were attributable to AD dementia in 2010. Conclusions: Alarger number of deaths are attributable to ADdementia in theUnited States each year than the number (,84,000 in 2010) reported on death certificates. © 2014 American Academy of Neurology.


Aggarwal N.T.,Rush University Medical Center | Aggarwal N.T.,Rush Alzheimers Disease Center | Wilson R.S.,Rush University Medical Center | Beck T.L.,Rush University Medical Center | And 4 more authors.
Psychosomatic Medicine | Year: 2014

Objective: Exposure to acute and chronic stress can affect learning and memory, but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample. Methods: Participants included 6207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging Project. Two to five in-home assessments were completed over an average of 6.8 years of follow-up and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a six-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment. Results: Mixed-effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B =-0.0379, standard error = 0.0025, p <.001) and a faster rate of cognitive decline (stress × time interaction: B =-0.0015, standard error = 0.0004, p <.001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age, or education. Conclusions: Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults 65 years and older. Copyright © 2014 by the American Psychosomatic Society.


Bruno A.M.,Franklin University | Huang J.Y.,Franklin University | Bennett D.A.,Rush Alzheimers Disease Center | Bennett D.A.,Rush University Medical Center | And 3 more authors.
Neurobiology of Aging | Year: 2012

Intracellular Ca 2+ dysregulation is an underlying component of Alzheimer's disease (AD) pathophysiology, and recent evidence implicates the ryanodine receptor (RyR) in the disease pathway. Three genes code for different RyR isoforms and each gene transcript gives rise to several alternatively spliced messenger RNAs (mRNAs). These variants confer distinct functionality to the RyR channel, such as altering Ca 2+ release properties or subcellular localization. Changes in RyR isoform expression and alternative splicing have not been examined for potential roles in AD pathogenesis. Here, we compare mRNA levels of the RyR2 and RyR3 isoforms as well as specific alternatively spliced variants across vulnerable brain regions from postmortem samples of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. We find an increase in RyR2 transcripts in MCI brains compared with no cognitive impairment. In addition, there is a reduction in a RyR2 splice variant, associated with an antiapoptotic function, in MCI and AD brains. These alterations in RyR expression at early disease stages may reflect the onset of pathologic mechanisms leading to later neurodegeneration. © 2012 Elsevier Inc.


Wilson R.S.,Rush Alzheimers Disease Center | Hebert L.E.,Rush Institute for Health Aging | Scherr P.A.,Rush Institute for Health Aging | Dong X.,Rush Institute for Health Aging | And 5 more authors.
Neurology | Year: 2012

Objective: To test the hypothesis that hospitalization in old age is associated with subsequent cognitive decline. Methods: As part of a longitudinal population-based cohort study, 1,870 older residents of an urban community were interviewed at 3-year intervals for up to 12 years. The interview included a set of brief cognitive tests from which measures of global cognition, episodic memory, and executive function were derived. Information about hospitalization during the observation period was obtained from Medicare records. Results: During a mean of 9.3 years, 1,335 of 1,870 persons (71.4%) were hospitalized at least once. In a mixed-effects model adjusted for age, sex, race, and education, the global cognitive score declined a mean of 0.031 unit per year before the first hospitalization compared with 0.075 unit per year thereafter, a more than 2.4-fold increase. The posthospital acceleration in cognitive decline was also evident on measures of episodic memory (3.3-fold increase) and executive function (1.7-fold increase). The rate of cognitive decline after hospitalization was not related to the level of cognitive function at study entry (r = 0.01, p = 0.88) but was moderately correlated with rate of cognitive decline before hospitalization (r=0.55, p=0.021). More severe illness, longer hospital stay, and older age were each associated with faster cognitive decline after hospitalization but did not eliminate the effect of hospitalization. Conclusion: In old age, cognitive functioning tends to decline substantially after hospitalization even after controlling for illness severity and prehospital cognitive decline. Copyright © 2012 by AAN Enterprises, Inc.


Wilson R.S.,Rush Alzheimers Disease Center | Wilson R.S.,Rush University Medical Center | Segawa E.,Rush Alzheimers Disease Center | Boyle P.A.,Rush University Medical Center | Bennett D.A.,Rush Alzheimers Disease Center
Neurology | Year: 2012

Objective: To test the hypothesis that late-life participation in mentally stimulating activities affects subsequent cognitive health. Methods: Analyses are based on 1,076 older persons without dementia at study onset participating in a longitudinal cohort study. They completed annual clinical evaluations for a mean of 4.9 years. Each evaluation included administration of a self-report scale about participation in mentally stimulating activities and a battery of cognitive performance tests. Previously established measures of cognitively stimulating activity and cognitive function were derived. We assessed the temporal sequence of activity changes in relation to functional changes in a series of cross-lagged panel models adjusted for age, sex, and education. Results: During the observation period, cognitive activity participation (estimate of mean annual change=-0.066, SE = 0.005, p < 0.001) and cognitive functioning (estimate=-0.077, SE = 0.005, p < 0.001) declined at rates that were moderately correlated (r = 0.44, p < 0.001). The level of cognitive activity in a given year predicted the level of global cognitive function in the following year, but the level of global cognition did not predict the subsequent level of cognitive activity participation. Cognitive activity showed the same pattern of unidirectional associations with measures of episodic and semantic memory, but its associations with working memory were bidirectional. Conclusions: The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning. Copyright © 2012 by AAN Enterprises, Inc.


Wilson R.S.,Rush Alzheimers Disease Center | Wilson R.S.,Rush University Medical Center | Segawa E.,Rush Alzheimers Disease Center | Boyle P.A.,Rush University Medical Center | Bennett D.A.,Rush Alzheimers Disease Center
Neurology | Year: 2012

Objective: To test the cognitive dedifferentiation hypothesis that cognitive abilities become increasingly correlated in late life. Methods: Participants are 174 older persons without dementia at the beginning of a longitudinal clinical-pathologic cohort study. At annual intervals for 6 to 15 years prior to death, they completed a battery of cognitive performance tests from which previously established composite measures of episodic memory, semantic memory, working memory, and perceptual speed were derived. At death, there was a uniform neuropathologic assessment and levels of diffuse plaques, neuritic plaques, and neurofibrillary tangles were summarized in a composite measure. Change in the 4 cognitive outcomes was analyzed simultaneously in a mixed-effects model that allowed rate of decline to accelerate at a variable point before death. Results: On average, cognitive decline before the terminal period was relatively gradual, and rates of change in different cognitive domains were moderately correlated, ranging from 0.25 (episodic memory-working memory) to 0.46 (episodic memory-semantic memory). By contrast, cognition declined rapidly during the terminal period, and rates of change in different cognitive functions were strongly correlated, ranging from 0.83 (working memory-perceptual speed) to 0.89 (episodic memory-semantic memory, semantic memory-working memory). Higher level of plaques and tangles on postmortem examination was associated with faster preterminal decline and earlier onset of terminal decline but not with rate of terminal decline or correlations between rates of change in different cognitive functions. Conclusion: In the last years of life, covariation among cognitive abilities sharply increases consistent with the cognitive dedifferentiation hypothesis. Copyright © 2012 by AAN Enterprises, Inc.


Verghese J.,Yeshiva University | Ayers E.,Yeshiva University | Barzilai N.,Yeshiva University | Bennett D.A.,Rush Alzheimers Disease Center | And 5 more authors.
Neurology | Year: 2014

Objective: To report incidence and risk factors for motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints. Methods: We examined incidence rates of MCR in 3,128 adults aged 60 years and older, MCRand dementia-free at baseline, participating in 4 US-based cohort studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of modifiable risk factors with risk of MCR were computed using Cox models. Results: Over a median follow-up time of 3.2 years, 823 of the 3,128 participants met MCR criteria. The overall age- and sex-adjusted incidence of MCR was 65.2/1,000 person-years (95% CI: 53.3-77.1), and ranged from 50.8/1,000 person-years to 79.6/1,000 person-years in the individual cohorts. MCR incidence was higher with older age but there were no sex differences. In the pooled sample adjusted for age, sex, education, and cohort source, strokes (HR 1.42, 95%CI: 1.14-1.77), Parkinson disease (HR 2.52, 95% CI: 1.68-3.76), depressive symptoms (HR 1.65, 95%CI: 1.28-2.13), sedentariness (HR 1.76, 95%CI: 1.44-2.17), and obesity (HR 1.39, 95% CI: 1.17-1.65) predicted risk of incident MCR. Conclusions: The incidence of MCR is high in older adults. Identification of modifiable risk factors for MCR will improve identification of high-risk individuals and help develop interventions to prevent cognitive decline in aging. © 2014 American Academy of Neurology.


Shah R.C.,Rush University Medical Center | Shah R.C.,Rush Alzheimers Disease Center
Drugs and Aging | Year: 2011

Alzheimers disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary foodstuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better understanding of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65 years and supplemented by other articles known to meet the inclusion criteria, revealed that only two medical foods, AC-1202 and Souvenaid® with Fortasyn Connect™, have clinical trial results available for discussion. As medical food development for AD is a relatively new endeavour, a window of opportunity exists for all stakeholders to develop a comprehensive framework for assuring that medical food interventions for AD achieve the highest possible scientific and ethical standards to warrant commercialization. © 2011 Adis Data Information BV. All rights reserved.

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