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D A Bennett

Publications and source records attributed to D A Bennett.

At least 37 records · Page 2Linked to original sources
PubMed2004

Relationship between Alzheimer's disease clinical stage and Gq/11 in subcellular fractions of frontal cortex.

Alzheimer's disease (AD) is associated with impaired coupling of cell surface muscarinic cholinergic receptors to G proteins of the Gq/11 class in brain. This alteration may contribute to progression of cognitive impairment during the course of the disease. We hypothesized that increasing severity of cognitive impairment would be related to decreased levels of Gq/11 detected in key subcellular fractions made from postmortem brain tissue. In this study, we used Western blotting to determine the quantity of Gq/11alpha in P2, synaptic plasma membrane, cytoplasm, microsomal membrane, and lipid raft fractions prepared from superior frontal cortex gray matter of 25 patients with clinical AD confirmed by post-mortem examination. Multiple linear regression analysis that adjusted for age, sex, and education showed a linear relationship between frontal cortex synaptic plasma membrane Gq/11alpha levels and severity of cognitive impairment determined by Mini Mental State score measured proximate to death.

Age Factors↗
PubMed2004

Diabetes mellitus and progression of rigidity and gait disturbance in older persons.

BACKGROUND: Parkinsonian-like signs, including rigidity, gait disturbance, and bradykinesia, are common and progressive in old age and are associated with morbidity and mortality. Few risk factors for these signs have been identified. Diabetes mellitus, also a common chronic condition in old age and known to be associated with physical and neurologic disability, may be associated with parkinsonian-like signs. OBJECTIVE: To examine the relation of diabetes to four parkinsonian-like signs. METHODS: Participants were 822 older Catholic clergymen and women who were without clinically diagnosed Parkinson disease or dementia at baseline. For up to 9 years, they had uniform annual evaluations, which included a modified version of the motor portion of the Unified Parkinson's Disease Rating Scale, from which previously established measures of four specific parkinsonian-like signs were derived. Participants were evaluated for the presence of diabetes, based on direct medication inspection and history. RESULTS: Diabetes was present in 128 (15.6%) participants. In random effects models controlling for age, sex, and education, diabetes was associated with worsening rigidity (p < 0.01) and gait (p < 0.05), over an average of 5.6 years of follow-up, but not with change in bradykinesia or tremor. The presence of stroke did not substantially affect the association of diabetes with rigidity but reduced the association of diabetes with gait to a trend (p = 0.08). CONCLUSION: Diabetes may be a previously unrecognized risk factor for progression of parkinsonian-like signs in older persons.

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PubMed2004

Blood pressure and late-life cognitive function change: a biracial longitudinal population study.

OBJECTIVE: To examine the relation of blood pressure (BP) to subsequent decline in cognitive function among persons age 65 or over. METHODS: All persons age 65 or over in a geographically defined community were invited to participate in a longitudinal study of problems of the elderly. Interviews were conducted in the participants' homes and included two BP measures and four tests of cognitive function. Follow-up interviews 3 and 6 years after baseline repeated the cognitive function tests. These analyses included 4,284 individuals who had baseline and at least one follow-up measure of cognitive function. The average of z scores of the individual cognitive function tests was used as a global measure of cognitive function. RESULTS: In random effects analyses controlling for age, sex, education, and race, there was no significant linear association of either systolic or diastolic BP with 6-year change in global cognitive function score. There was no significant curvilinear association with systolic BP. In tests for a curvilinear association with diastolic BP, there was a suggestion of increased decline among those with low or high diastolic BP (p = 0.03 for the quadratic diastolic term). At baseline, 50% of participants took some type of medication affecting BP. CONCLUSION: In this community population where BP treatment was common, there was no association of either high systolic or high diastolic BP at the beginning of the observation interval with 6-year cognitive decline.

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PubMed2004

Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology.

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. The effect of cerebral infarctions on the likelihood of dementia from AD pathology is not well understood. METHODS: The study included 153 deceased Catholic clergy who participated in the Religious Orders Study. Annual evaluations, including 19 tests of cognitive function, were performed to determine a diagnosis of dementia and level of cognitive abilities proximate to death. At autopsy, neuritic and diffuse plaques and neurofibrillary tangles were counted and combined into a standardized summary measure of AD pathology. Number, volume, side, and distribution of old macroscopic infarctions were recorded. Analyses included logistic and linear regression, adjusting for age, sex, and education. RESULTS: The AD pathology score ranged from 0 to 2.93 units, and 54 persons had infarctions. There was no relationship between AD pathology and infarctions (r = 0.04, p = 0.56). Each unit of AD pathology increased the odds of dementia by 4.40-fold (95% CI = 2.33 to 8.32), and this was essentially unchanged after accounting for infarctions. The presence of one or more infarctions independently increased the odds of dementia by 2.80-fold (95% CI = 1.26 to 6.21). There was no interaction between AD pathology and infarctions to further increase the likelihood of dementia (p = 0.39). The number, size, and distribution of infarctions added to the odds of dementia but also did not show an interaction with AD pathology. Similar results were found in analyses with global cognitive function and five different cognitive systems. CONCLUSION: Cerebral infarctions independently contribute to the likelihood of dementia but do not interact with AD pathology to increase the likelihood of dementia beyond their additive effect.

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PubMed2004

MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD.

With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In the present study, 27 patients diagnosed with mild cognitive impairment (MCI) received a high-resolution MRI scan at baseline and were followed with yearly clinical evaluations. Ten of the 27 patients converted to AD during a 36-month period following the baseline clinical evaluation. Hippocampal and entorhinal cortex volumes derived from the baseline scan were compared to determine which of these two regions, known to be pathologically involved very early in the course of AD, could best differentiate MCI converters from non-converters. Although both entorhinal and hippocampal volumes were found to be independent predictors of the likelihood of conversion to AD, it was the right hemisphere entorhinal volume that best predicted conversion with a concordance rate of 93.5%.

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PubMed2004

Influence of behavioral symptoms on rates of institutionalization for persons with Alzheimer's disease.

BACKGROUND: Recent studies indicate that behavioral symptoms may play a key role in decisions to institutionalize persons with Alzheimer's disease (AD), but the specific types of behavior that contribute to this increased risk have not been reliably identified. The relationship between behavioral symptoms and time to institutionalization was evaluated in a 4-year longitudinal study. METHOD: A total of 410 persons with the clinical diagnosis of AD completed annual clinical evaluations to assess cognitive impairment, functional limitations, delusions, hallucinations, depressive symptoms and physical aggression. Participation rates among survivors exceeded 90% for four follow-up evaluations with complete ascertainment of mortality and institutionalization. Time to institutionalization was evaluated using proportional hazards regression models in relation to time-varying clinical features. RESULTS: In multivariate models, adjusted for demographic and social variables, four clinical features emerged as the predominant predictors of institutionalization: cognitive impairment level, physical aggression, hallucinations and depressive symptoms. These associations were virtually unchanged in analyses controlling for mortality. CONCLUSIONS: Specific behavioral symptoms are important independent risk factors for institutionalization in persons with AD. Because behavioral symptoms are susceptible to therapy, efforts to modify or prevent these symptoms deserve careful consideration as a means to delay institutionalization for persons with this disease.

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PubMed2004

The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults.

CONTEXT: Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute. OBJECTIVE: To evaluate the efficacy of chitosan for weight loss in overweight and obese adults. DESIGN AND SETTING: A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002. PARTICIPANTS: A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y) INTERVENTIONS: Participants were randomly assigned to receive 3 g chitosan/day (n=125) or placebo (n=125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts. MAIN OUTCOME MEASURES: The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life. RESULTS: In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P=0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P<0.01). There were no significant differences between groups for any of the other measured outcomes. CONCLUSION: In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo.

Adult↗
PubMed2004

Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline.

BACKGROUND: Dementia can be caused by severe niacin insufficiency, but it is unknown whether variation in intake of niacin in the usual diet is linked to neurodegenerative decline. We examined whether dietary intake of niacin was associated with incident Alzheimer's disease (AD) and cognitive decline in a large, prospective study. METHODS: This study was conducted in 1993-2002 in a geographically defined Chicago community of 6158 residents aged 65 years and older. Nutrient intake was determined by food frequency questionnaire. Four cognitive tests were administered to all study participants at 3 year intervals in a 6 year follow up. A total of 3718 participants had dietary data and at least two cognitive assessments for analyses of cognitive change over a median 5.5 years. Clinical evaluations were performed on a stratified random sample of 815 participants initially unaffected by AD, and 131 participants were diagnosed with 4 year incident AD by standardised criteria. RESULTS: Energy adjusted niacin intake had a protective effect on development of AD and cognitive decline. In a logistic regression model, relative risks (95% confidence intervals) for incident AD from lowest to highest quintiles of total niacin intake were: 1.0 (referent) 0.3 (0.1 to 0.6), 0.3 (0.1 to 0.7), 0.6 (0.3 to 1.3), and 0.3 (0.1 to 0.7) adjusted for age, sex, race, education, and ApoE e4 status. Niacin intake from foods was also inversely associated with AD (p for linear trend = 0.002 in the adjusted model). In an adjusted random effects model, higher food intake of niacin was associated with a slower annual rate of cognitive decline, by 0.019 standardised units (SU) per natural log increase in intake (mg) (p = 0.05). Stronger associations were observed in analyses that excluded participants with a history of cardiovascular disease (beta = 0.028 SU/year; p = 0.008), those with low baseline cognitive scores (beta = 0.023 SU/year; p = 0.02), or those with fewer than 12 years' education (beta = 0.035 SU/year; p = 0.002) CONCLUSION: Dietary niacin may protect against AD and age related cognitive decline.

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PubMed2004

Blood glucose and risk of cardiovascular disease in the Asia Pacific region.

OBJECTIVE: To assess the shape and strength of the association between usual blood glucose and cardiovascular disease (CVD) in Asian and Australasian cohorts and to determine the impact of adjusting for other determinants of CVD risk and excluding people with diabetes. RESEARCH DESIGN AND METHODS: Relative risk estimates and 95% CIs were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk on individual participant data from 17 cohort studies. Repeat measurements of blood glucose were used to adjust for regression dilution bias. RESULTS: Fasting blood glucose data were available for 237,468 participants, and during approximately 1.2 million person-years of follow-up, there were 1,661 stroke and 816 ischemic heart disease (IHD) events. Data were also available on 27,996 participants with nonfasting glucose measurements. Continuous positive associations were demonstrated between usual fasting glucose and the risks of CVD down to at least 4.9 mmol/l. Overall, each 1 mmol/l lower usual fasting glucose was associated with a 21% (95% CI 18-24%) lower risk of total stroke and a 23% (19-27%) lower risk of total IHD. The associations were similar in men and women, across age-groups, and in Asian compared with Australasian (Australia and New Zealand) populations. Adjusting for potential confounders or removing those with diabetes as baseline did not substantially affect the associations. Associations for nonfasting glucose were weaker than those with fasting glucose. CONCLUSIONS: Fasting blood glucose is an important determinant of CVD burden, with considerable potential benefit of usual blood glucose lowering down to levels of at least 4.9 mmol/l.

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PubMed2004

Depressive symptoms and cognitive decline in a community population of older persons.

BACKGROUND: An association between depressive symptoms and cognitive decline has been observed in selected cohorts of older people, but studies of defined populations have had conflicting results. OBJECTIVE: To test whether the level of depressive symptoms predicted the rate of cognitive decline in a biracial community of older persons. METHODS: 4392 older people (88% of those eligible) from a defined community in Chicago completed two or three structured interviews at approximately three year intervals for an average of 5.3 years. At the baseline interview, the number of depressive symptoms was assessed with a 10 item version of the Center for Epidemiologic Studies Depression scale. Cognitive function was assessed at each interview with four performance tests, from which a previously established measure of global cognition was derived. Random effects models were used to assess change in cognition and its relation to depressive symptoms, controlling for age, sex, race, education, and baseline cognitive function. RESULTS: Participants reported a median of one depressive symptom at baseline (interquartile range, 0 to 2). For each depressive symptom, the rate of cognitive decline increased by a mean of about 5%. Results were not substantially changed when persons with cognitive impairment at baseline were excluded, or when chronic illness or participation in cognitively stimulating activities was controlled, and the association was not modified by age, sex, race, or education. CONCLUSIONS: The results suggest that depressive symptoms predict cognitive decline in old age.

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PubMed2004

Premorbid proneness to distress and episodic memory impairment in Alzheimer's disease.

BACKGROUND: Chronic stress has been associated with impaired episodic memory, but the association of premorbidly experienced distress with memory function in Alzheimer's disease is unknown. OBJECTIVE: To investigate the link between proneness to distress and Alzheimer's disease. METHODS: Participants were 363 persons with clinically diagnosed Alzheimer's disease. At baseline, a knowledgeable informant rated each person's premorbid personality (that is, before dementia onset) along five dimensions, one of which was the tendency to experience psychological distress. Participants underwent structured clinical evaluations at baseline and then annually for up to four years. Each evaluation included 17 cognitive tests from which previously established measures of episodic memory, visuoconstruction, repetition, and naming were derived. RESULTS: In a series of random effects models adjusted for age, sex, and education, premorbid distress proneness was associated with baseline impairment in episodic memory but not with impairment in other cognitive domains, or with change in any cognitive domain. No other trait was related to baseline function or rate of decline in any cognitive domain. CONCLUSIONS: The results suggest that premorbid proneness to experience psychological distress is related to level of impairment in episodic memory in persons with Alzheimer's disease, but neither distress proneness nor other personality traits are related to disease progression.

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PubMed2003

Proneness to psychological distress is associated with risk of Alzheimer's disease.

BACKGROUND: Chronic stress is associated with hippocampal damage and impaired memory in animals and humans. OBJECTIVE: To examine this relationship with clinical and pathologic data from the Religious Orders Study. METHODS: Older Catholic clergy members underwent annual clinical evaluations, which included clinical classification of Alzheimer's disease (AD) and detailed cognitive function testing from which composite measures of global cognition and specific cognitive functions were derived. At the baseline evaluation, participants completed a measure of the tendency to experience psychological distress, a stable personality trait that served as an indicator of susceptibility to negative emotional states across the life span. More than 90% of participants who died underwent a uniform postmortem examination of the brain from which summary measures of AD pathology were derived. The association of distress proneness with incident AD and cognitive decline and with measures of AD pathology was examined in analyses adjusted for selected demographic and clinical variables. RESULTS: During a mean of 4.9 years of follow-up, 140 persons developed AD. Those high in distress proneness (90th percentile) had twice the risk of developing AD than those low in distress proneness (10th percentile). Distress proneness was related to decline in episodic memory but not in other cognitive domains, with a >10-fold increase in episodic memory decline in those high in distress proneness compared with those low in the trait. Among those who died, however, distress proneness was not related to common measures of AD pathology. CONCLUSION: Proneness to experience psychological distress is a risk factor for AD, an effect independent of AD pathologic markers such as cortical plaques and tangles.

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PubMed2003

Rate of cognitive decline and mortality in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is associated with increased mortality, but survival in those with the disease varies widely. It is uncertain how much of the variation in survival is due to individual differences in rate of disease progression. METHODS: During a 4-year period, 354 persons with AD underwent annual clinical evaluations that included administration of 17 cognitive function tests, from which global and specific measures of cognitive function were derived. A growth curve approach was used to assess individual rates of cognitive decline and proportional hazards models adjusted for age, sex, and education to examine the associations of baseline level of cognition and rate of cognitive decline with mortality. RESULTS: During the 4-year study period, 242 persons survived and 112 died. At baseline, the global measure of cognition ranged from -1.68 to 1.36 (mean = 0.03, SD = 0.57), with higher scores indicating better function. Baseline level of cognition was not related to mortality (p = 0.12). Global cognition declined an average of 0.56 unit/year, with substantial heterogeneity (SD = 0.41). To determine mortality risk, persons were divided into quartiles based on rate of cognitive decline and survival contrasted in the quartile with the least decline with survival in each remaining quartile, adjusting for baseline level of cognition. Compared with those with the least decline, risk of death was increased more than threefold in the subgroup with mild decline, more than fivefold in those with moderately rapid decline, and more than eightfold in those with the most rapid decline. Similar results were found after controlling for baseline health and disability and in analyses using specific cognitive function measures. CONCLUSION: Mortality in AD is strongly associated with rate of cognitive decline.

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PubMed2003

Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons.

BACKGROUND: Depressive symptoms in old age have been associated with risk of Alzheimer disease (AD), but it is uncertain whether they are an independent risk factor for disease or an early clinical sign of its underlying pathology. METHODS: A group of 130 older Catholic nuns, priests, and brothers underwent detailed annual clinical evaluations and brain autopsy at death. The evaluations included administration of a modified 10-item Center for Epidemiologic Studies Depression Scale (CES-D) and 19 cognitive performance tests and clinical classification of dementia and AD. On postmortem examination, neuritic plaques, diffuse plaques, and neurofibrillary tangles in tissue samples from four cortical regions were counted, and a previously established composite measure of cortical plaque and tangle density (range 0 to 2.98) was derived. All analyses were adjusted for age, sex, and education. RESULTS: Participants reported a mean 1.5 depressive symptoms (SD 1.6) on the CES-D scale averaged across evaluations. In a logistic regression model, the odds of clinically diagnosed AD proximate to death increased by 1.33 (95% CI 1.01 to 1.76) for each depressive symptom and by 8.41 (95% CI 3.49 to 20.26) for each unit on the composite measure of pathology. In subsequent analyses, depressive symptoms were not related to level of pathology and did not modify the relation of pathology to clinical AD. In a series of linear regression models that controlled for pathology, depressive symptoms were related to level of cognitive function proximate to death and did not modify the association of pathology with cognition. CONCLUSION: The association of depressive symptoms with clinical AD and cognitive impairment appears to be independent of cortical plaques and tangles.

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PubMed2003

Cognitive activity and cognitive decline in a biracial community population.

BACKGROUND: Frequent participation in cognitively stimulating activities has been associated with reduced risk of AD in several prospective studies. However, the association of cognitive activity with cognitive decline, the principal manifestation of AD, is not well understood. METHODS: More than 4,000 older residents of a geographically defined biracial community of Chicago were interviewed at approximately 3-year intervals for an average of 5.3 years. Each interview included administration of four cognitive function tests from which a previously established global measure was derived. At baseline, each person rated frequency of participation in cognitively stimulating activities (e.g., reading a magazine) from which a previously established composite measure of cognitive activity was derived. RESULTS: Cognitive activity scores ranged from 1 to 5 (mean = 3.14, SD = 0.66), with higher scores indicating more frequent participation. More frequent cognitive activity was associated with reduced cognitive decline during follow-up. In a model that controlled for baseline level of cognition, age, sex, race, and education, a 1-point increase in cognitive activity score was associated with an approximately 19% decrease in annual rate of cognitive decline (p < 0.001). This effect remained when we controlled for depressive symptoms and chronic medical conditions (p < 0.001), and when we excluded persons with evidence of memory impairment at baseline (p < 0.001). CONCLUSION: Frequent participation in cognitively stimulating activities is associated with reduced cognitive decline in older persons.

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PubMed2003

Education modifies the relation of AD pathology to level of cognitive function in older persons.

OBJECTIVE: To test the hypothesis that years of formal education modifies the relation of AD pathology to level of cognitive function. METHODS: A total of 130 older Catholic clergy participating in the Religious Orders Study underwent annual cognitive function testing and brain autopsy at the time of death. Individual cognitive function tests were z-scored and averaged to yield a global measure of cognitive function and summary measures of five different cognitive abilities. Neuritic and diffuse plaques and neurofibrillary tangles were counted in separate 1 mm(2) areas of maximal density. Counts were converted to standard scores by dividing by their SD, and combined to yield a global AD pathology score and summary scores of each postmortem index. Linear regression was used to examine the relation of education and AD pathology scores to level of cognitive function proximate to death, controlling for age and sex. Subsequent analyses tested the interaction between education and each AD pathology score to determine whether education modified the relation of AD pathology to level of cognitive function. Additional analyses examined these associations on five specific cognitive abilities. RESULTS: Both years of formal education (regression coefficient = 0.073, p = 0.0001) and the global AD pathology score (regression coefficient = -0.689, p < 0.0001) were related to level of cognitive function. When an interaction term between education and AD pathology was added to the model, the association between a unit of AD pathology and level of cognitive function was 0.088 (p = 0.0078) standard unit less for each year of education than the level predicted from the model without the interaction term. Whereas neuritic plaques, diffuse plaques, and neurofibrillary tangles were all strongly related to cognitive function, education only modified the relation of neuritic plaques (p = 0.002) and diffuse plaques (p = 0.03) to cognition, but not neurofibrillary tangles. In analyses examining five different cognitive abilities, the interaction between education and the neuritic plaque score was strongest for perceptual speed and weakest for episodic memory. CONCLUSIONS: These data provide strong evidence that the relation between senile plaques and level of cognitive function differs by years of formal education.

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PubMed2003

Gender, cognitive decline, and risk of AD in older persons.

BACKGROUND: Cross-sectional studies suggest gender differences in cognitive function and risk of AD in older persons. However, longitudinal studies comparing change in cognitive function and risk of AD in men and women have had mixed results. The authors investigated gender differences in rate of decline for different cognitive systems and for risk of developing AD. METHODS: Participants were from the Religious Orders Study, a longitudinal, clinical-pathologic study of aging and AD in older Catholic nuns, priests, and brothers. Longitudinal data were available from 577 older women and 271 older men, who completed an average of 5.8 annual evaluations with more than 95% follow-up participation in survivors. The evaluations included 21 neuropsychological tests, from which summary measures of global cognitive function and 5 functional domains were formed, and clinical classification of AD. RESULTS: Random effects models were used to analyze change in cognitive function, and proportional hazards models were used to assess risk of incident AD. On average, men and women declined in all abilities during the 8-year period but did not differ in annual rates of change in analyses that controlled for age, education, and initial level of cognitive function. Risk of incident AD did not differ between men and women. Furthermore, results were unchanged after controlling for possession of the apolipoprotein-epsilon4 allele. Duration of estrogen use was related to rate of global cognitive decline and visuospatial abilities in women but did not influence comparisons between men and women in cognitive decline. CONCLUSIONS: The results suggest that patterns of cognitive decline and incidence of AD are similar in older men and women.

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