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David A Bennett

Publications and source records attributed to David A Bennett.

At least 91 records · Page 5Linked to original sources
PubMed2003

Dietary fats and the risk of incident Alzheimer disease.

BACKGROUND: Few studies have investigated the effects of dietary fats on the development of Alzheimer disease. We examined the associations between intake of specific types of fat and incident Alzheimer disease in a biracial community study. METHODS: We performed clinical evaluations on a stratified random sample of 815 community residents aged 65 years and older who were unaffected by Alzheimer disease at baseline and who completed a food-frequency questionnaire a mean of 2.3 years before clinical evaluation. RESULTS: After a mean follow-up of 3.9 years, 131 persons developed Alzheimer disease. Intakes of saturated fat and trans-unsaturated fat were positively associated with risk of Alzheimer disease, whereas intakes of omega-6 polyunsaturated fat and monounsaturated fat were inversely associated. Persons in the upper fifth of saturated-fat intake had 2.2 times the risk of incident Alzheimer disease compared with persons in the lowest fifth in a multivariable model adjusted for age, sex, race, education, and apolipoprotein E epsilon4 allele status (95% confidence interval, 1.1-4.7). Risk also increased with consumption of trans-unsaturated fats, beginning with the second fifth of intake (relative risk, 2.4 compared with the lowest fifth; 95% confidence interval, 1.1-5.3). We observed linear inverse associations between Alzheimer disease and vegetable fat (P =.002), and, after further adjustment for other types of fat, marginally significant associations with intake of omega-6 polyunsaturated fat (P =.10 for trend) and monounsaturated fat (P =.10 for trend). Intakes of total fat, animal fat, and dietary cholesterol were not associated with Alzheimer disease. CONCLUSION: High intake of unsaturated, unhydrogenated fats may be protective against Alzheimer disease, whereas intake of saturated or trans-unsaturated (hydrogenated) fats may increase risk.

Aged↗
PubMed2003

Parkinsonianlike signs and risk of incident Alzheimer disease in older persons.

BACKGROUND: Parkinsonianlike signs are common in older persons, but little is known about how their severity or rate of progression is related to the development of Alzheimer disease (AD) or decline in cognition. OBJECTIVE: To examine the association of progression of parkinsonianlike signs with incident AD and cognitive decline. DESIGN: Longitudinal cohort study. PARTICIPANTS AND SETTING: For up to 8 years, 824 older Catholic clergy members without clinical evidence of AD or Parkinson disease at baseline underwent annual clinical evaluations that included a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS), detailed cognitive function testing, and clinical classification of AD. MAIN OUTCOME MEASURES: Clinically diagnosed AD and change in global and specific measures of cognitive function. RESULTS: During an average of 4.6 years of observation, 114 persons developed AD. The global UPDRS score increased in 79% of participants, who were divided into tertiles with the least, moderate, or most rapid progression. We examined the relationship of progression to disease risk in a proportional hazards model that controlled for baseline global UPDRS and demographic variables. Compared with the 21% without progression, risk of AD more than doubled in the subgroup with the least progression (P =.08), more than tripled in the moderate subgroup (P =.02), and increased more than 8-fold in the subgroup with the most rapid progression (P<.001). This effect was mainly due to worsening gait and rigidity. Rate of change on the global UPDRS measure was inversely correlated with rate of change on a global measure of cognitive function (r = -0.64). CONCLUSION: Progression of parkinsonianlike signs in old age is associated with decline in cognitive function and the development of AD.

Aged↗
PubMed2003

Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease. OBJECTIVE: To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease. DESIGN: Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease. PATIENTS: A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. MAIN OUTCOME MEASURES: Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria. RESULTS: A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions. CONCLUSION: Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

Aged↗
PubMed2003

Alzheimer disease in the US population: prevalence estimates using the 2000 census.

CONTEXT: Current and future estimates of Alzheimer disease (AD) are essential for public health planning. OBJECTIVE: To provide prevalence estimates of AD for the US population from 2000 through 2050. DESIGN: Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. SETTING: A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. PARTICIPANTS: Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence. Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. RESULTS: In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. CONCLUSION: The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.

Aged↗
PubMed2003

Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease.

BACKGROUND: The status of nerve growth factor (NGF) levels during the prodromal phase of Alzheimer disease (AD), characterized by mild cognitive impairment (MCI), remains unknown. OBJECTIVE: To investigate whether cortical and/or hippocampal NGF levels are altered in subjects with MCI or different levels of AD severity. DESIGN AND MAIN OUTCOME MEASURES: An NGF enzyme-linked immunosorbent assay determined protein levels in the hippocampus and 5 cortical areas in people clinically diagnosed as having no cognitive impairment, MCI, mild AD, or severe AD. SETTING AND PATIENTS: Subjects were from the Rush Religious Orders Study and the University of Pittsburgh Alzheimer's Disease Research Center (Pittsburgh, Pa). RESULTS: We found no changes in cortical or hippocampal NGF levels across groups; in MCI, levels did not correlate with an increase in choline acetyltransferase activity in these regions. CONCLUSION: Brain NGF levels appear sufficient to support the cholinergic plasticity changes seen in MCI and remain stable throughout the disease course.

Aged↗
PubMed2003

Update on mild cognitive impairment.

Mild cognitive impairment (MCI) refers to persons whose memory or other cognitive abilities are not normal, but who do not have clinically diagnosed dementia. MCI has received considerable attention in the medical literature over the past few years. There were 63 original reports in the English language literature with the term "mild cognitive impairment" in the title in 2001 and 2002, in contrast to only 26 articles in the prior decade. Although criteria for MCI are not a matter of secure agreement, a consensus is emerging that MCI is common, is associated with significant mortality and morbidity, particularly the development of AD, and is due, in large part, to the same pathologic processes responsible for Alzheimer's disease (AD). Current research efforts are geared towards understanding factors that contribute to the development of dementia among persons with MCI and towards intervention studies aimed at preventing the development of dementia among persons with MCI.

Brain↗
PubMed2003

Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density.

Intracellular accumulation of PHFtau in Alzheimer's disease (AD) disrupts the neuronal cytoskeleton and other neuronal machinery and contributes to axonal and dendritic degeneration, and neuronal death. Furthermore, amyloid-beta (Abeta) has been reported to be toxic to neurons and neurites. While loss of presynaptic elements is an established feature of AD, the nature and extent of dendritic degeneration has been infrequently studied. We investigated MAP2-immunoreactive dendrites using a novel method of high-throughput quantification and also measured cortical thickness and the densities of NeuN-immunoreactive neurons, PHFtau neurofibrillary tangles (NFTs), and Abeta plaque burden in the subiculum in AD and elderly controls. Corrected for atrophy, the "dendritic arborization index" was significantly reduced by up to 66% in all three layers of the subiculum. Laminar thickness was reduced by an average 33% and there was a marked reduction in neuron density of approximately 50%. As expected, NFTs and Abeta plaques were significantly increased in AD. Dendritic arborization indices negatively correlated with NFT densities while no significant correlations were found with Abeta plaque densities. The pattern of dendritic loss in the subiculum and the correlations with NFT densities respectively suggest that deafferentation and intrinsic neurofibrillary degeneration both may contribute to dendritic loss in AD.

Aged↗
PubMed2003

Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology.

Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved. We correlated levels of hippocampal choline acetyltransferase (ChAT) activity with the extent of AD lesions in subjects from the Religious Order Study, including cases with no cognitive impairment (NCI), MCI, and with mild to moderate AD. Hippocampal ChAT activity levels were also determined in a group of end-stage AD patients who were enrolled in the University of Pittsburgh Alzheimer's Disease Research Center. MCI subjects were characterized with increased hippocampal ChAT activity. This elevation was no longer present in mild AD cases, which were not different from NCI subjects. Severe AD cases showed markedly depleted hippocampal ChAT levels. In NCI, MCI, and mild-moderate AD, there was a positive correlation between hippocampal ChAT activity levels and progression of neuritic plaque pathology in entorhinal cortex and hippocampus. A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages. We hypothesize that cholinergic changes in the hippocampus of MCI subjects reflect a compensatory response to the progressive denervation of the hippocampus by lost entorhinal cortex input. Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.

Aged↗
PubMed2003

Design of the Chicago Health and Aging Project (CHAP).

The design of the Chicago Health and Aging Project (CHAP) is described. CHAP is a longitudinal population study of common chronic health problems of older persons, especially of risk factors for incident Alzheimer's disease, in a biracial neighborhood of the south side of Chicago. Special attention is given to three unusual design features of the study. One feature is that clinical evaluation for Alzheimer's disease is confined to a stratified random sample of all participants. This feature results in substantial cost savings and substantially less bias than screening approaches but has the disadvantages of adding analytic complexity and requiring the use of indirect means to identify a disease-free cohort for the development of incident Alzheimer's disease. The second unusual feature is efficiently combining in analyses the successive independent multiple samples that are drawn, one from each data collection cycle. The third unusual feature is entering successive age cohorts of community residents into the study as they attain 65 years of age. This has the advantages of enhancing direct investigation of the effect of age on the action of risk factors for Alzheimer's disease and direct examination of cohort effects. The interaction of these features is described, especially as they pertain to a study in which data are collected in successive waves. The results from these waves must be combined for effective analysis of the relation among risk factors and incident disease.

Age Factors↗
PubMed2002

Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study.

CONTEXT: Oxidative processes have been suggested as elements in the development of Alzheimer disease (AD), but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown. OBJECTIVE: To examine whether intake of antioxidant nutrients, vitamin E, vitamin C, and beta carotene is associated with incident AD. DESIGN, SETTING, AND PARTICIPANTS: Prospective study, conducted from 1993 to 2000, of individuals selected in a stratified random sample of community-dwelling residents. The 815 residents 65 years and older were free of AD at baseline and were followed up for a mean of 3.9 years. They completed food frequency questionnaires an average of 1.7 years after baseline. MAIN OUTCOME MEASURE: Incident AD diagnosed in clinical evaluations with standardized criteria. RESULTS: Increasing vitamin E intake from foods was associated with decreased risk of developing AD after adjustment for age, education, sex, race, APOE epsilon 4, and length of follow-up. Relative risks (95% confidence intervals [CIs]) from lowest to highest quintiles of intake were 1.00, 0.71 (0.24-2.07), 0.62 (0.26-1.45), 0.71 (0.27-1.88), and 0.30 (0.10-0.92) (P for trend =.05). The protective association of vitamin E was observed only among persons who were APOE epsilon 4 negative. Adjustment for other dietary factors reduced the protective association. After adjustment for baseline memory score, the risk was 0.36 (95% CI, 0.11-1.17). Intake of vitamin C, beta carotene, and vitamin E from supplements was not significantly associated with risk of AD. CONCLUSION: This study suggests that vitamin E from food, but not other antioxidants, may be associated with a reduced risk of AD. Unexpectedly, this association was observed only among individuals without the APOE epsilon 4 allele.

Aged↗
PubMed2002

Participation in cognitively stimulating activities and risk of incident Alzheimer disease.

CONTEXT: Frequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease (AD), but prospective data regarding an association are lacking. OBJECTIVE: To test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD. DESIGN: Longitudinal cohort study with baseline evaluations performed between January 1994 and July 2001 and mean follow-up of 4.5 years. PARTICIPANTS AND SETTING: A total of 801 older Catholic nuns, priests, and brothers without dementia at enrollment, recruited from 40 groups across the United States. At baseline, they rated frequency of participation in common cognitive activities (eg, reading a newspaper), from which a previously validated composite measure of cognitive activity frequency was derived. MAIN OUTCOME MEASURES: Clinical diagnosis of AD by a board-certified neurologist using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria and change in global and specific measures of cognitive function, compared by cognitive activity score at baseline. RESULTS: Baseline scores on the composite measure of cognitive activity ranged from 1.57 to 4.71 (mean, 3.57; SD, 0.55), with higher scores indicating more frequent activity. During an average of 4.5 years of follow-up, 111 persons developed AD. In a proportional hazards model that controlled for age, sex, and education, a 1-point increase in cognitive activity score was associated with a 33% reduction in risk of AD (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Results were comparable when persons with memory impairment at baseline were excluded and when terms for the apolipoprotein E epsilon4 allele and other medical conditions were added. In random-effects models that controlled for age, sex, education, and baseline level of cognitive function, a 1-point increase in cognitive activity was associated with reduced decline in global cognition (by 47%), working memory (by 60%), and perceptual speed (by 30%). CONCLUSION: These results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.

Aged↗
PubMed2002

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.

Acetylcholine↗
PubMed2002

The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period.

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.

Aged↗
PubMed2002

Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment.

In Alzheimer's disease (AD), loss of cortical and hippocampal choline acetyltransferase (ChAT) activity has been correlated with dementia severity and disease duration, and it forms the basis for current therapies. However, the extent to which reductions in ChAT activity are associated with early cognitive decline has not been well established. We quantified ChAT activity in the hippocampus and four cortical regions (superior frontal, inferior parietal, superior temporal, and anterior cingulate) of 58 individuals diagnosed with no cognitive impairment (NCI; n = 26; mean age 81.4 +/- 7.3 years), mild cognitive impairment (MCI; n = 18; mean age 84.5 +/- 5.7), or mild AD (n =14; mean age 86.3 +/- 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects with end-stage AD (mean age 81.4 +/- 4.3 years) and compared to inferior parietal cortex ChAT levels of the other three groups. Only the end-stage AD group had ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT activity was unchanged in the inferior parietal, superior temporal, and anterior cingulate cortices compared to NCI. In contrast, ChAT activity in the superior frontal cortex was significantly elevated above normal controls in MCI subjects, whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT activity was significantly higher in MCI subjects than in either NCI or AD. Our results suggest that cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation. Thus, the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss. Of importance, the cholinergic system is capable of compensatory responses during the early stage of dementia. The upregulation in frontal cortex and hippocampal ChAT activity could be an important factor in preventing the transition of MCI subjects to AD.

Aged↗
PubMed2002

Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease.

Abnormally phosphorylated tau accumulates as neurofibrillary tangles and neuropil threads in older persons with and without Alzheimer's disease. The relationship between neurofibrillary tangles and neuropil threads and how they relate to cognitive function is unknown. This study investigated the relationship between phosphorylated tau lesions and cognitive function in 31 persons participating in the Religious Orders Study, a prospective, longitudinal clinicopathological study of aging and Alzheimer's disease. All subjects underwent detailed neuropsychological performance testing within a year of death and evidenced a spectrum of cognitive performance ranging from normal abilities to mild dementia. Measures of neurofibrillary tangle density and phosphorylated tau immunoreactive structures (predominantly neuropil threads) in the entorhinal and perirhinal cortices by quantitative image analysis were significantly correlated (r = 0.5). In multiple linear regression analyses controlling for age, sex, and education, parahippocampal neurofibrillary tangles and neuropil threads were significantly lower in persons without cognitive impairment compared to those with mild cognitive impairment and/or Alzheimer's disease. Further, neurofibrillary tangles were significantly correlated to measures of episodic memory but not other cognitive abilities; neuropil tangles were not significantly related to memory or other cognitive functions. These data indicate that phosphorylated tau pathology in the ventromedial temporal lobe develop prior to the onset of clinical dementia and their presence is associated with cognitive impairment, particularly impairment of episodic memory.

Aged↗
PubMed2002

Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer's disease.

A multitiered strategy was adopted to assess tau conformational changes within fibrillar lesions during the progression of Alzheimer's disease (AD). Anti-tau monoclonal antibodies whose epitopes are distributed across much of the molecule were used to probe vulnerable brain regions in 37 clinically staged cases obtained from the Religious Orders Study. In this way, tau conformational changes were evaluated as the disease progressed from early cognitive decline to AD. These analyses revealed three main findings. First, the presence of granulovacuolar and fibrillar lesions correlates with several measures of episodic memory, suggesting that these lesions significantly contribute to cognitive dysfunction. Second, neuropil threads precede the appearance of neurofibrillary tangles that in turn precede the appearance of neuritic plaques. Third, tau structural changes, or "conformational signatures," emerged as a result of in situ reactivity to a subset of antibodies and nonreactivity to others, thereby reflecting the underlying status of the tau molecule within the fibrillar lesions. These signatures allowed us to document a sequence of tau conformational changes that occur during AD and to correlate these changes with episodic memory deficits. Furthermore, we were able to compare conformational signatures of tau among different lesion types and determine that the molecular profile of tau is lesion-specific.

Aged↗
PubMed2002

Aging effects on memory encoding in the frontal lobes.

Functional magnetic resonance imaging (fMRI) was used to compare frontal-lobe activation in younger and older adults during encoding of words into memory. Participants made semantic or nonsemantic judgments about words. Younger adults exhibited greater activation for semantic relative to nonsemantic judgments in several regions, with the largest activation in the left inferior frontal gyrus. Older adults exhibited greater activation for semantic judgments in the same regions. but the extent of activation was reduced in left prefrontal regions. In older adults, there was a significant association between behavioral tests of declarative and working memory and extent of frontal activation. These results suggest that age-associated decreases in memory ability may be due to decreased frontal-lobe contributions to the initial encoding of experience.

Adult↗