Alzheimer Disease: Aggarwal NT

Aggarwal NT. · Rush Alzheimer's Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · Panminerva Med. · Pubmed #18091670 No free full text.

Abstract: A wide spectrum of cognitive ability is seen in older persons, ranging from intact cognitive function to clinically manifested dementia. The term mild cognitive impairment (MCI) is increasingly used to refer to individuals who have some cognitive impairment but do not meet the criteria for dementia. Despite a lack of consensus about precisely how to define MCI, researchers agree that the condition is relatively common in older people, and data suggest that MCI may be associated with an increased risk of Alzheimer's disease, parkinsonian signs and disability. Presently, the clinical assessment of MCI should include a detailed evaluation of cognitive functioning and the use of structural MRI can provide important diagnostic and prognostic information. Although therapeutic trials in MCI using the Choline acetylcholinesterase's have been disappointing with short term affects noted, pharmacologic prevention studies for MCI, are underway and may provide valuable data to prevent the development of this condition.

Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, Wilson RS. · Rush Alzheimer's Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #16801647 No free full text.

Abstract: OBJECTIVE: To examine the relation of National Institute on Aging-Reagan (NIA-Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive function in persons without dementia or mild cognitive impairment (MCI). METHODS: More than 2,000 persons without dementia participating in the Religious Orders Study or the Memory and Aging Project agreed to annual detailed clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed five cognitive domains, including episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. A total of 134 persons without cognitive impairment died and underwent brain autopsy and postmortem assessment for AD pathology using NIA-Reagan neuropathologic criteria for AD, cerebral infarctions, and Lewy bodies. Linear regression was used to examine the relation of AD pathology to level of cognitive function proximate to death. RESULTS: Two (1.5%) persons met NIA-Reagan criteria for high likelihood AD, and 48 (35.8%) met criteria for intermediate likelihood; 29 (21.6%) had cerebral infarctions, and 18 (13.4%) had Lewy bodies. The mean Mini-Mental State Examination score proximate to death was 28.2 for those meeting high or intermediate likelihood AD by NIA-Reagan criteria and 28.4 for those not meeting criteria. In linear regression models adjusted for age, sex, and education, persons meeting criteria for intermediate or high likelihood AD scored about a quarter standard unit lower on tests of episodic memory (p = 0.01). There were no significant differences in any other cognitive domain. CONCLUSIONS: Alzheimer disease pathology can be found in the brains of older persons without dementia or mild cognitive impairment and is related to subtle changes in episodic memory.

Wilson RS, Aggarwal NT, Barnes LL, Bienias JL, Mendes de Leon CF, Evans DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, 600 S Paulina Ave, Ste 1038, Chicago, IL 60612, USA. · Arch Neurol. · Pubmed #19506138 No free full text.

Abstract: OBJECTIVE: To assess mortality associated with mild cognitive impairment (MCI) and Alzheimer disease (AD) among older African Americans and whites from an urban community. DESIGN: Longitudinal population-based observational study. SETTING: Four adjacent neighborhoods in Chicago, Illinois. PARTICIPANTS: Persons deemed free of dementia in a previous wave of data collection (n = 1715) underwent detailed clinical evaluation: 802 had no cognitive impairment (46.8%), 597 had MCI (34.8%), 296 had AD (17.3%), and 20 had other forms of dementia (1.2%). MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: During as many as 10 years of observation (mean [SD], 4.7 [3.0] years), 634 individuals died (37.0%). Compared with people without cognitive impairment, risk of death was increased by about 50% among those with MCI (hazard ratio [95% confidence interval], 1.48 [1.22-1.80]) and was nearly 3-fold greater among those with AD (2.84 [2.29-3.52]). These effects were seen among African Americans and whites and did not differ by race. Among participants with MCI, risk of death increased with more severe cognitive impairment, and this effect did not vary by race. A similar effect was seen among participants with AD, but it was slightly stronger for African Americans vs whites. In the MCI and AD groups, the association of cognitive impairment with survival was stronger for perceptual speed than for other cognitive functions. CONCLUSION: The presence and severity of MCI and AD are associated with reduced survival among African Americans, and these effects are comparable to those seen among whites.

Skarupski KA, McCann JJ, Bienias JL, Wolinsky FD, Aggarwal NT, Evans DA. · Rush Institute for Healthy Aging, 1645 W. Jackson, Chicago, IL, USA. · Home Health Care Serv Q. · Pubmed #19042238 No free full text.

Abstract: OBJECTIVES: To explore the association between adult day care (ADC) attendance and utilization of home-based formal services among people with Alzheimer's Disease (AD). METHODS: Data for this secondary analysis came from a longitudinal parent study of 457 subjects from 16 ADC programs and an Alzheimer's diagnostic center in metropolitan Chicago. We used the method of Generalized Estimating Equations to model the use of home-based formal services over time. RESULTS: Adjusting for relevant covariates, more days of ADC use at each follow-up was associated with decreased use of home-based formal services (coefficient = .25, p< .0001). Older, unmarried caregivers who are children of the care recipients had lower use of home-based services. DISCUSSION: Results suggest that ADC services may substitute for specific types of home-based formal services. The projected increase in AD prevalence over the next several decades warrants a clearer understanding of how people with AD use formal services.

Wilson RS, McCann JJ, Li Y, Aggarwal NT, Gilley DW, Evans DA. · Alzheimer's Disease Center, Institute for Health Aging, Department of Neurological Sciences, College of Nursing, Rush University Medical Center, 600 S. Paulina St., Suite 1038, Chicago, IL 60612, USA. · Am J Psychiatry. · Pubmed #17541050 links to  free full text

Abstract: OBJECTIVE: People with Alzheimer's disease are often placed in a nursing home, sometimes after using adult day care services. How affected persons function during this potentially difficult transition is not well understood. The aim of this study was to examine the associations of day care use and nursing home placement with the rate of cognitive decline in Alzheimer's disease. METHOD: The participants were 432 older persons with Alzheimer's disease who were recruited from health care settings in the Chicago area. At baseline, they lived in the community and were using day care services a mean 1.7 days per week. At 6-month intervals for up to 4 years, they completed nine cognitive tests from which a composite measure of global cognition was derived. RESULTS: On average, cognition declined at a gradually increasing rate during the study period. Nursing home placement was associated with a decrease in the level of cognition and an acceleration in the rate of cognitive decline. Day care use at baseline was not related to cognitive decline in initial analyses, but it interacted with nursing home placement such that higher level of day care use substantially reduced association of placement with accelerated cognitive decline. Education interacted with placement such that more schooling was associated with a greater increase in cognitive decline upon nursing home placement, but prior day care use also attenuated this association. CONCLUSIONS: Nursing home placement is associated with accelerated short-term cognitive decline in Alzheimer's disease. Prior experience in adult day care may lessen this association.

Aggarwal NT, Wilson RS, Beck TL, Bienias JL, Bennett DA. · Rush Alzheimer's Disease Center, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL 60612, USA. · Arch Neurol. · Pubmed #17172617 links to  free full text

Abstract: BACKGROUND: Little is known about motor function in mild cognitive impairment (MCI) and its relation to the risk of Alzheimer disease (AD). OBJECTIVE: To examine motor function in persons with MCI and its relation to risk of AD. DESIGN: Longitudinal cohort study. SETTING: More than 40 Catholic religious orders across the United States. PARTICIPANTS: We studied 816 older Catholic clergy members from the Religious Orders Study. At the baseline evaluation, they were classified as having no cognitive impairment (n = 558), MCI (n = 198), or dementia (n = 60). MAIN OUTCOME MEASURES: Motor function was assessed at baseline using performance-based measures of upper and lower extremity function and a modified version of the motor section of the Unified Parkinson's Disease Rating Scale, from which previously established measures of parkinsonian signs were derived. Clinical evaluations for dementia and AD were repeated annually for up to 10 years. All analyses controlled for age, sex, educational level, and possession of at least 1 apolipoprotein E epsilon4 allele. RESULTS: At baseline, individuals with MCI had impaired motor function relative to those without cognitive impairment and superior motor function vs those with dementia. Among those with MCI, baseline levels of lower extremity motor performance, parkinsonian gait, and bradykinesia were inversely related to risk of AD, even after controlling for clinical stroke. Thus, a person with impaired lower limb performance or parkinsonian gait (10th percentile) was 2 to 3 times more likely to develop AD than a person with good lower limb function (90th percentile). CONCLUSIONS: Persons with MCI also have impaired motor function, and the degree of impairment in lower extremity function is related to the risk of AD.

Bennett DA, Schneider JA, Aggarwal NT, Arvanitakis Z, Shah RC, Kelly JF, Fox JH, Cochran EJ, Arends D, Treinkman AD, Wilson RS. · Rush Alzheimer's Disease Center, Chicago, Ill, USA. · Neuroepidemiology. · Pubmed #17035694 No free full text.

Abstract: We developed prediction rules to guide the clinical diagnosis of Alzheimer's disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. We compared the positive predictive value of the clinical diagnosis in the two community-based studies to the positive predictive value of the clinical diagnosis of AD made by standard clinical practice in a clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD; the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141 study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria for AD; the results were lower but acceptable for those with possible AD (26 of 37, 70.3%). The results were similar in secondary analyses using alternate neuropathologic criteria for AD. The clinical diagnosis of AD can be made in community-based studies without the use of informant interviews, neuroimaging, blood work or routine case conferencing. This approach holds promise for reducing the operational costs of epidemiologic studies of aging and AD.

Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. · Rush Institute for Healthy Aging, Rush University Medical Center, 1645 W. Jackson #675, Chicago, IL 60612, USA. · J Alzheimers Dis. · Pubmed #16917153 No free full text.

Abstract: CONTEXT: It is currently not known whether dietary intakes of folate and vitamins B12 and B6, co-factors in the methylation of homocysteine, protect against Alzheimer's disease. OBJECTIVE: To examine the association between risk of incident Alzheimer's disease and dietary intakes of folate, vitamin B-12, and vitamin B-6. DESIGN: Prospective cohort study. SETTING: Geographically defined biracial Chicago community. PARTICIPANTS: 1,041 residents, aged 65 years and older, initially free of Alzheimer's disease and followed a median 3.9 years for the development of incident disease. MAIN OUTCOME MEASURE: Probable Alzheimer's disease identified through structured clinical neurological evaluation using standardized criteria. RESULTS: A total of 162 persons developed incident Alzheimer's disease during follow-up. In logistic regression models adjusted for age, sex, race, education, cognitive activities, APOE-epsilon4, and dietary intakes of vitamin E in food and total niacin, there was no association between risk of developing Alzheimer's disease and quintiles of folate intake or of vitamin B-12 intake. The adjusted odds ratio was 1.6 (95% confidence interval: 0.5, 5.2) for persons in the highest quintile of total folate intake (median of 752.7 microg/d) compared with persons in the lowest quintile of intake (median, 202.8 microg/d). Compared with persons in the first quintile of total vitamin B-12 intake (median, 3.1 microg/d) the odds ratio was 0.6 (95% confidence interval: 0.2, 1.6) for persons in the fifth quintile of intake (median, 20.6 microg/d). Intake of vitamin B-6 was not associated with incident Alzheimer's disease after control for dietary intakes of vitamin E and total niacin. CONCLUSION: Dietary intakes of folate, vitamin B-12, or vitamin B-6 do not appear to be associated with the development of Alzheimer's disease.

Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. · Rush Alzheimer's Disease Center, Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #16894105 No free full text.

Abstract: OBJECTIVE: To examine the extent to which persons with mild cognitive impairment (MCI) have an increased risk of Alzheimer disease (AD) and a more rapid rate of decline in cognitive function compared to similar persons without cognitive impairment. METHOD: Participants were 786 community-based persons (221 with MCI and 565 without cognitive impairment) from the Rush Memory and Aging Project, an ongoing longitudinal clinical-pathologic study of common chronic conditions of old age. All participants underwent detailed annual clinical and neuropsychological evaluations. The authors examined the risk of incident AD and rate of change in global cognitive function among persons with MCI and those without cognitive impairment; all statistical models controlled for age, sex, and education. RESULTS: Over an average of 2.5 years of follow-up, 57 persons with MCI (25.8%) developed AD, a rate 6.7 times higher than those without cognitive impairment. In addition, persons with MCI declined considerably more rapidly each year on a measure of global cognitive function than those without cognitive impairment. CONCLUSIONS: Mild cognitive impairment is associated with a greatly increased risk of incident Alzheimer disease and a more rapid rate of decline in cognitive function.

Wilson RS, Li Y, Aggarwal NT, McCann JJ, Gilley DW, Bienias JL, Barnes LL, Evans DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA. · Int J Geriatr Psychiatry. · Pubmed #16534773 No free full text.

Abstract: OBJECTIVE: To test the association of rate of cognitive decline, an indicator of the severity of the underlying disease process, with risk of death in Alzheimer's disease (AD). METHODS: A total of 472 persons with clinically diagnosed AD were recruited from a memory disorders clinic and day care centers in the Chicago area. They completed a uniform clinical evaluation at baseline and a battery of nine cognitive tests at six-month intervals for a mean of about three years. A previously established measure of global cognition was derived from the nine tests. RESULTS: During follow-up, 168 persons (36%) died. In a proportional hazards model that controlled for age, sex, race, education, and baseline level of cognition, individual rate of global cognitive decline, estimated with least squares regression, was linearly related to mortality risk. Thus, a person declining minimally (increase of 0.04 unit per year, 90th percentile) was 2.7 times less likely to die during the study period than a person declining rapidly (decrease of 0.76 unit per year, 10th percentile). Controlling for baseline disability did not substantially affect results. The association of cognitive decline with mortality was substantially stronger for white persons compared to African Americans and in those with less compared to more education. CONCLUSION: The results indicate that the rate at which cognition declines in AD is robustly related to survival.

Aggarwal NT, Bienias JL, Bennett DA, Wilson RS, Morris MC, Schneider JA, Shah RC, Evans DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Armour Academic Center, Chicago, IL 60612, USA. · Neuroepidemiology. · Pubmed #16493200 No free full text.

Abstract: The relationship between smoking status and incident Alzheimer's disease (AD) was investigated in a random stratified sample of a biracial community in Chicago. Analyses are based on 1,064 persons (of 1,134 evaluated) who had data on smoking status, disease incidence, and key covariates such as apolipoprotein allele status. During a mean of about 4 years of follow-up, 170 persons met criteria for incident AD. Current smoking was associated with increased risk of incident AD (OR = 3.4, 95% CI = 1.4-8.0) compared to persons who never smoked. There was no apparent increase in risk of AD for former smokers compared to persons who never smoked (OR = 0.9, 95% CI = 0.5-1.7). Apolipoprotein E allele status modified this association in that former smokers with a upsilon4 allele were less likely to develop AD (p = 0.04) than those who never smoked. Former smokers also appeared to have a reduced risk of developing AD as their pack-years of smoking increased (p = 0.02)such that the odds of developing AD increased by 50% for every 10 years of smoking cessation (OR = 1.3, CI = 0.9-1.7). The results suggest that older people who currently smoke are more likely to develop AD compared to those who never smoked; the relation between those who used to smoke but quit and the risk of AD is complex and requires further research.

Wilson RS, Tang Y, Aggarwal NT, Gilley DW, McCann JJ, Bienias JL, Evans DA. · Rush Alzheimer's Disease Center, Rush Institute for Healthy Aging, and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · Neuroepidemiology. · Pubmed #16352909 No free full text.

Abstract: The relation of psychotic symptoms to cognitive decline and mortality in Alzheimer's disease (AD) was examined during a mean of 2.2 years in 478 persons selected from clinical settings. Psychotic symptoms were ascertained at baseline and cognition was assessed semiannually with nine tests from which a global measure was formed. In analyses that controlled for age, sex, race, and education, hallucinations (29.6%), especially visual ones, were associated with more rapid global cognitive decline and increased mortality, even after controlling for baseline level of cognition and use of antipsychotic medication, and the association with mortality increased with higher level of education. Delusions and misperceptions were not strongly related to cognitive decline or mortality. The results suggest that hallucinations in Alzheimer's disease, particularly visual ones, are associated with more rapid progression.

McCann JJ, Hebert LE, Li Y, Wolinsky FD, Gilley DW, Aggarwal NT, Miller JM, Evans DA. · Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL 60612, USA. · Gerontologist. · Pubmed #16326657 No free full text.

Abstract: PURPOSE: This longitudinal study examined whether the use of adult day care services delayed time to nursing home placement in persons with Alzheimer's disease. DESIGN AND METHODS: Two hundred and eighteen adult day care clients with Alzheimer's disease were recruited from 16 adult day programs in a large metropolitan area. Two hundred and ninety eight persons with Alzheimer's disease but not using adult day care were recruited from a federally funded Alzheimer's diagnostic center and frequency matched to adult day care users on age, gender, race, and level of cognitive impairment. Participants were followed at 3-month intervals for up to 48 months. Cox proportional hazards models were used to examine the effects of adult day care and other fixed and time-varying factors on risk of nursing home placement. RESULTS: Risk of nursing home placement increased significantly with the number of days of adult day care attendance, with this effect being substantially greater for men (hazard ratio or HR = 1.33; confidence interval or CI = 1.18-1.49) than for women (HR = 1.09; CI = 1.00-1.18). Participant disability and hospitalizations and caregiver age and burden were independent predictors, but their inclusion in the model did not alter the risk associated with adult day care. IMPLICATIONS: More severe disease and greater caregiver burden did not explain the increased risk of nursing home placement among adult day care users with Alzheimer's disease. Rather, it appears that other unmeasured factors, such as a proclivity to institutionalize, may account for the association of adult day care to nursing home risk.

Barnes LL, Wilson RS, Li Y, Aggarwal NT, Gilley DW, McCann JJ, Evans DA. · Rush Alzheimer's Disease Center, Depeartment of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. · Am J Geriatr Psychiatry. · Pubmed #16286439 No free full text.

Abstract: OBJECTIVE: Alzheimer disease (AD) is the leading cause of dementia in older persons, but little is known about racial differences in its clinical manifestations. The purpose of the current study was to examine the association of race with rate of cognitive decline in AD. METHODS: Older persons with clinically diagnosed AD were recruited from healthcare settings. At 6-month intervals for up to 4 years, they completed a battery of nine cognitive tests from which a previously established measure of global cognition was derived. Follow-up data were available on 452 participants (27.6% African American, 68.8% women), 88.1% of those eligible. RESULTS: A growth curve approach was used to estimate individual paths of change in global cognition. In a model that controlled for age and education, African Americans had a lower level of global cognition at baseline than non-African Americans, but declined at a 25% slower rate on average. In additional models, there was no indication that the association of race with cognitive decline varied by age, gender, or education. CONCLUSION: The rate of cognitive decline in AD appears to be slower in African Americans than non-African Americans.

Aggarwal NT, Wilson RS, Beck TL, Bienias JL, Bennett DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #16227534 links to  free full text

Abstract: BACKGROUND: Little is known about factors that predict transition from mild cognitive impairment to Alzheimer's disease (AD). OBJECTIVE: To examine the relation of impairment in different cognitive systems to risk of developing AD in persons with mild cognitive impairment. METHODS: Participants are 218 older Catholic clergy members from the Religious Orders Study. At baseline, they met criteria for mild cognitive impairment based on a uniform clinical evaluation that included detailed cognitive testing. Evaluations were repeated annually for up to 10 years. Analyses were controlled for age, sex, and education. RESULTS: Eighty two persons (37.6%) developed AD. In separate analyses, episodic memory, semantic memory, working memory, and perceptual speed, but not visuospatial ability, were associated with risk of AD, but when analysed together only episodic memory and perceptual speed were associated with AD incidence, with the effect for episodic memory especially strong. Overall, those with impaired episodic memory were more than twice as likely to develop AD as those with impairment in other cognitive domains (relative risk (RR) = 2.45; 95% confidence interval (CI): 1.53 to 3.92), and they experienced more rapid cognitive decline. Lower episodic memory performance was associated with increased risk of AD throughout the observation period, whereas impairment in other cognitive domains was primarily associated with risk during the following year but not thereafter. CONCLUSION: Among persons with mild cognitive impairment, episodic memory impairment is associated with a substantial and persistent elevation in risk of developing AD compared to impairment in other cognitive systems.

Aggarwal NT, Wilson RS, Beck TL, Bienias JL, Berry-Kravis E, Bennett DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612-3872, USA. · Neurocase. · Pubmed #15804918 No free full text.

Abstract: Possession of one or more copies of the apolipoprotein E (APOE) epsilon4 allele is a known risk factor for Alzheimer's disease (AD), but it is uncertain whether the epsilon4 allele is associated with disease incidence among persons with mild cognitive impairment (MCI). We addressed this issue with data from the Religious Orders Study. Participants were 181 older Catholic clergy members who met criteria for MCI based on a uniform structured clinical evaluation; 56 (30.9%) had at least one epsilon4 allele. Clinical evaluations, which included clinical classification of dementia and AD, were repeated annually. During a mean of 5.7 years of observation, 79 persons (43.6%) developed AD. In a proportional hazards model that controlled for age, sex, and education, possession of an epsilon4 allele was associated with a 93% increase in the risk of developing Alzheimer's disease (95% CI; 1.02, 2.63). There was a marginally significant reduction in the effect of epsilon4 in older compared to younger participants (p=.053). The results suggest that possession of an epsilon4 allele does increase risk of AD in persons with MCI.

Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA. · Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL 60612, USA. · Am J Clin Nutr. · Pubmed #15699242 links to  free full text

Abstract: BACKGROUND: High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is inversely associated with Alzheimer disease. OBJECTIVE: We examined whether food intakes of vitamin E, alpha-tocopherol equivalents (a measure of the relative biologic activity of tocopherols and tocotrienols), or individual tocopherols would protect against incident Alzheimer disease and cognitive decline over 6 y in participants of the Chicago Health and Aging Project. DESIGN: The 1993-2002 study of community residents aged >or=65 y included the administration of 4 cognitive tests and clinical evaluations for Alzheimer disease. Dietary assessment was by food-frequency questionnaire. RESULTS: Tocopherol intake from food was related to the 4-y incidence of Alzheimer disease determined by logistic regression in 1041 participants who were clinically evaluated (n=162 incident cases) and to change in a global cognitive score determined by mixed models in 3718 participants. Higher intakes of vitamin E (relative risk: 0.74 per 5 mg/d increase; 95% CI: 0.62, 0.88) and alpha-tocopherol equivalents (relative risk: 0.56 per 5 mg/d increase; 95% CI: 0.32, 0.98) were associated with a reduced incidence of Alzheimer disease in separate multiple-adjusted models that included intakes of saturated and trans fats and docosahexaenoic acid. alpha- and gamma-Tocopherol had independent associations. In separate mixed models, a slower rate of cognitive decline was associated with intakes of vitamin E, alpha-tocopherol equivalents, and alpha- and gamma-tocopherols. CONCLUSION: The results suggest that various tocopherol forms rather than alpha- tocopherol alone may be important in the vitamin E protective association with Alzheimer disease.

Wilson RS, Li Y, Aggarwal NT, Barnes LL, McCann JJ, Gilley DW, Evans DA. · Rush Alzheimer's Disease Center, Rush University Medical Center, 600 South Paulina, Suite 1038, Chicago, IL 60612, USA. · Neurology. · Pubmed #15477538 No free full text.

Abstract: OBJECTIVE: To test the hypothesis that higher level of education is related to more rapid cognitive decline in Alzheimer disease (AD). METHODS: Participants are older persons with clinically diagnosed AD recruited from health care facilities in the Chicago area. At 6-month intervals for up to 4 years, they underwent uniform structured clinical evaluations that included administration of nine cognitive performance tests from which a composite measure of global cognition was derived. Analyses are based on 494 persons with follow-up data (89.3% of those eligible). In mixed models that allowed for linear and nonlinear decline, the authors first accounted for the effects of age on cognition and then tested the relation of education to rate of cognitive decline. RESULTS: Global cognitive decline had linear and nonlinear components, resulting in a gradually accelerating course of decline. Age was related to linear but not nonlinear decline, with more rapid decline observed in younger compared with older persons. Higher educational level was related to more rapid global cognitive decline, as hypothesized, with education related to the nonlinear but not the linear component of decline. CONCLUSION: Higher educational attainment is associated with a slightly accelerated rate of cognitive decline in Alzheimer disease.

Bennett DA, Wilson RS, Schneider JA, Evans DA, Aggarwal NT, Arnold SE, Cochran EJ, Berry-Kravis E, Bienias JL. · Rush Alzheimer's Disease Center, Chicago, Illinois 60612, USA. · Neurology. · Pubmed #12552039 No free full text.

Abstract: OBJECTIVE: To test the hypothesis that the APOE epsilon4 allele is associated with the clinical manifestations of AD through an association with the pathologic hallmarks of disease. METHODS: Participants were older Catholic nuns, priests, and brothers who agreed to annual neurologic and neuropsychological evaluation for AD and other common neurologic conditions and brain autopsy at the time of death. There were 77 persons without dementia and 51 with probable AD; 38 participants had one or more epsilon4 alleles. RESULTS: In logistic regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with the likelihood of clinical AD (odds = 3.46, 95% CI = 1.44 to 8.33). However, controlling for the effect of AD pathology, the association of the epsilon allele with clinical AD was reduced by >50% and was no longer significant (odds = 1.58, 95% CI = 0.56 to 4.43). Similarly, in linear regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with level of cognitive function proximate to death (regression coefficient = -0.477, p = 0.005). However, after controlling for the effect of AD pathology, the association of the epsilon4 allele with level of cognition was reduced by >80% and was no longer significant (regression coefficient = -0.093). Similar results were found in analyses using separate measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles, and in analyses of five different cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability). CONCLUSIONS: The APOE epsilon4 allele appears to be associated with the clinical manifestations of AD through an association with the pathologic hallmarks of AD rather than another mechanism.

Wilson RS, Bennett DA, Bienias JL, Aggarwal NT, Mendes De Leon CF, Morris MC, Schneider JA, Evans DA. · Department of Neurological Sciences, Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #12499482 No free full text.

Abstract: BACKGROUND: Participation in cognitively stimulating activities is hypothesized to be associated with risk of AD, but knowledge about this association is limited. METHODS: A biracial community in Chicago was censused, persons aged 65 years and older were asked to participate in an interview, and 6,158 of 7,826 (79%) eligible persons did so. As part of the interview, persons rated current frequency of participation in seven cognitive activities (e.g., reading a newspaper) and nine physical activities (e.g., walking for exercise) from which composite measures of cognitive and physical activity frequency were derived. Four years later, 1,249 of those judged free of AD were sampled for a detailed clinical evaluation of incident disease and 842 (74% of those eligible) participated. RESULTS: The composite measure of cognitive activity ranged from 1.28 to 4.71 (mean 3.30; SD 0.59), with higher scores indicating more frequent activity. A total of 139 persons met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD on clinical evaluation. In a logistic regression model adjusted for age, education, sex, race, and possession of the APOE epsilon4 allele, a one-point increase in cognitive activity score was associated with a 64% reduction in risk of incident AD (OR 0.36; 95% CI 0.20 to 0.65). By contrast, weekly hours of physical activity (mean 3.5; SD 5.1) was not related to disease risk (OR 1.04; 95% CI 0.98 to 1.10). Education was associated with risk of AD and a similar trend was present for occupation, but these effects were substantially reduced when cognitive activity was added to the model. CONCLUSION: Frequency of participation in cognitively stimulating activities appears to be associated with risk of AD and may partially explain the association of educational and occupational attainment with disease risk.

Wilson RS, Barnes LL, Mendes de Leon CF, Aggarwal NT, Schneider JS, Bach J, Pilat J, Beckett LA, Arnold SE, Evans DA, Bennett DA. · Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, 1645 West Jackson Boulevard, Suite 675, Chicago, IL 60612, USA. · Neurology. · Pubmed #12177369 No free full text.

Abstract: BACKGROUND: Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. METHODS: Participants are Catholic clergy members who were aged > or =65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. RESULTS: At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. CONCLUSIONS: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Wilson RS, Schneider JA, Barnes LL, Beckett LA, Aggarwal NT, Cochran EJ, Berry-Kravis E, Bach J, Fox JH, Evans DA, Bennett DA. · Rush Alzheimer's Disease Center and Rush Institute for Healthy Aging, 1645 W Jackson Blvd, Suite 675, Chicago, IL 60612, USA. · Arch Neurol. · Pubmed #12117364 links to  free full text

Abstract: CONTEXT: Impairment of episodic memory is an early and defining feature of Alzheimer disease (AD). The apolipoprotein E (APOE) epsilon 4 allele is known to influence risk of AD but it has been difficult to establish whether it affects episodic memory differently from other cognitive functions. OBJECTIVE: To examine the association of epsilon 4 with decline in different cognitive systems. DESIGN: Longitudinal cohort study. SETTING: More than 40 groups of Catholic clergy from across the United States. PARTICIPANTS: Older Catholic clergy members without clinical evidence of dementia at baseline underwent annual clinical evaluations for up to 6 years. Of 624 persons eligible for follow-up, 611 (98%) participated, of whom 161 (26%) had at least 1 epsilon 4 allele. They completed an average of 5.5 evaluations (range, 2-7). MAIN OUTCOME MEASURES: Incident AD and annual rates of change in episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. RESULTS: The presence of epsilon 4 was associated with risk of developing AD on follow-up (relative risk, 1.92; 95% confidence interval, 1.27-2.89). In a series of random effects models, epsilon 4 was associated with impaired baseline function in episodic memory and visuospatial ability and with more rapid decline in all domains. The effect of epsilon 4 on annual decline in episodic memory (>3-fold increase) was significantly stronger than its effect on decline in other cognitive systems (P<.01), and at baseline, its effect on episodic memory was marginally stronger than its effect on other cognitive domains (P =.06). CONCLUSION: The results suggest that the APOE epsilon 4 allele influences risk of AD by a relatively selective effect on episodic memory.