Rush Alzheimers Disease Center

Chicago, United States

Rush Alzheimers Disease Center

Chicago, United States
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Gallo D.A.,University of Chicago | Foster K.T.,University of Chicago | Wong J.T.,University of Chicago | Bennett D.A.,Rush University Medical Center | Bennett D.A.,Rush Alzheimers Disease Center
Neuropsychologia | Year: 2010

Alzheimer's Disease (AD) can reduce the effects of emotional content on memory for studied pictures, but less is known about false memory. In healthy adults, emotionally arousing pictures can be more susceptible to false memory effects than neutral pictures, potentially because emotional pictures share conceptual similarities that cause memory confusions. We investigated these effects in AD patients and healthy controls. Participants studied pictures and their verbal labels, and then picture recollection was tested using verbal labels as retrieval cues. Some of the test labels had been associated with a picture at study, whereas other had not. On this picture recollection test, we found that both AD patients and controls incorrectly endorsed some of the test labels that had not been studied with pictures. These errors were associated with medium to high levels of confidence, indicating some degree of false recollection. Critically, these false recollection judgments were greater for emotional compared to neutral items, especially for positively valenced items, in both AD patients and controls. Dysfunction of the amygdala and hippocampus in early AD may impair recollection, but AD did not disrupt the effect of emotion on false recollection judgments. © 2010 Elsevier Ltd.


Gallo D.A.,University of Chicago | Cramer S.J.,University of Chicago | Wong J.T.,University of Chicago | Bennett D.A.,Rush University Medical Center | Bennett D.A.,Rush Alzheimers Disease Center
Neuropsychologia | Year: 2012

Alzheimer's disease (AD) can impair metacognition in addition to more basic cognitive functions like memory. However, while global metacognitive inaccuracies are well documented (i.e., low deficit awareness, or anosognosia), the evidence is mixed regarding the effects of AD on local or task-based metacognitive judgments. Here we investigated local metacognition with respect to the confidence-accuracy relationship in episodic memory (i.e., metamemory). AD and control participants studied pictures of common objects and their verbal labels, and then took forced-choice picture recollection tests using the verbal labels as retrieval cues. We found that item-based confidence judgments discriminated between accurate and inaccurate recollection responses in both groups, implicating relatively spared metamemory in AD. By contrast, there was evidence for global metacognitive deficiencies, as AD participants underestimated the severity of their everyday problems compared to an informant's assessment. Within the AD group, individual differences in global metacognition were related to recollection accuracy, and global metacognition for everyday memory problems was related to task-based metacognitive accuracy. These findings suggest that AD can spare the confidence-accuracy relationship in recollection tasks, and that global and local metacognition measures tap overlapping neuropsychological processes. © 2012 Elsevier Ltd.


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 | 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.


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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