Biomedical subjects

David A Bennett

Publications and source records attributed to David A Bennett.

102 records · Page 6Linked to original sources

PubMed2002

Future directions for EPA Superfund research.

The EPA Office of Research and Development (ORD) identifies and prioritizes future research areas through a Waste Research Coordination Team. The team works together to plan the ORD Superfund research program, and it has members from each of the ORD laboratories as well as representatives from the Superfund office. Superfund scientists have identified several research topics in applied research areas to improve risk assessment methods and reduce uncertainty in site-specific risk assessments. Research areas include: dermal exposure models and toxicity values, improved methods for exposure factors, pharmaco-kinetic dose-response models, bioavailability and statistical methods. This paper presents ORD future research plans in response to these identified research areas.

Biological Availability↗

PubMed2002

Improved detection of substantia nigra pathology in Alzheimer's disease.

The role of substantia nigra pathology in Alzheimer's disease (AD) is uncertain. Detection of pathology may be obscured by intraneuronal neuromelanin and influenced by stains. We determined methods for optimal visualization of nigral pathology in 45 cases of AD. For detection of Lewy bodies (LBs), we compared ubiquitin and alpha-synuclein immunostains to hematoxylin and eosin (H&E). For neurofibrillary tangles (NFTs) and neuropil threads (NTs), we compared Gallyas silver and paired helical filament (PHF) immunostains, after bleaching of melanin, to modified Bielschowsky, Gallyas, and PHF alone. The number of LB cases was not different using the three stains. However, more LBs per section were detected using alpha-synuclein (z=4.88, p<0.001). Twice the number of cases exhibited NFT (z=8.21; p<0.001) and the mean NFT number per section was 2.8-5.2-fold greater, using Gallyas and PHF after bleaching compared to without bleaching (chi(2)=142.17; p<0.001). More NTs (z=6.54; p<0.001) were observed with PHF and Gallyas after bleaching. With optimal methods, we found LBs in 27%, NFTs in 89%, and NTs in all 45 AD cases. We show that detection of nigra pathology is influenced by histological method. Clinicopathological studies using these methods are needed to determine the role of nigral pathology in AD.

Aged↗

PubMed2002

Individual differences in rates of change in cognitive abilities of older persons.

The authors examined change in cognitive abilities in older Catholic clergy members. For up to 6 years, participants underwent annual clinical evaluations, which included a battery of tests from which summary measures of 7 abilities were derived. On average, decline occurred in each ability and was more rapid in older persons than in younger persons. However, wide individual differences were evident at all ages. Rate of change in a given domain was not strongly related to baseline level of function in that domain but was moderately associated with rates of change in other cognitive domains. The results suggest that change in cognitive function in old age primarily reflects person-specific factors rather than an inevitable developmental process.

Aged↗

PubMedDate not supplied

Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's disease.

Herein we review the role of apolipoprotein E (ApoE) in Alzheimer's disease (AD) and how ApoE interacts with various risk factors. ApoE is localized with the major pathological hallmarks of AD, extracellular amyloid deposits and intracellular neurofibrillary tangles. The ApoE4 allele is associated with the development of late-onset familial and sporadic AD. ApoE4 has a gene dose effect on the risk and age of onset of AD. ApoE mRNA and protein are found predominantly in astrocytes within the CNS. There is also a high expression of ApoE mRNA in the brains of people with sporadic AD. ApoE acts as a cholesterol transporter in the brain. Cholesterol controls amyloid production and deposition by regulating beta-secretase. In transgenic animal studies, ApoE4 expression causes neuropathology and behavioral deficits. We also discuss data from three different cohorts for AD in the general population, in different racial and ethnic groups and the role of the 4 allele in the clinical onset of the disease. Although the 4 allele is an important genetic risk factor for AD, it accounts for a fairly small fraction of disease in the population. The effect of the 4 allele on annual decline in episodic memory is significantly stronger than its effect on decline in other cognitive systems. Notably, the 2 allele has an equal and opposite effect. Thus, ApoE allele status influences risk of AD by a relatively selective effect on episodic memory. Mechanistically, the role of APoE in AD needs to be established in terms of its gene expression, which ultimately controls levels of various ApoE isoforms. Transcriptional regulation suggests complex regulation of this gene and the resultant ApoE protein in injured neurons. We discuss the characteristics of ApoE regulatory elements, including their interactions with different transcription factors, to understand ApoE gene expression. Thus, ApoE4 contributes to the pathogenesis of AD, but additional environmental risk factors will also be identified independent of ApoE and other genetic polymorphisms.

Alzheimer Disease↗

PubMedDate not supplied

Harm avoidance and disability in old age.

The relation of personality to disability in old age is not well understood. The authors examined the relation of harm avoidance, a trait indicating a tendency to worry, fear uncertainty, be shy, and tire easily, to disability in a group of 474 older persons without dementia. Participants completed the 35-item Harm Avoidance scale. Disability was assessed with the Rosow-Breslau scale, a self-report measure of physical mobility. Performance-based tests of lower limb functions were also administered from which composite measures of gait, balance, and strength were derived. In a logistic regression model controlled for age, sex, education, and lower limb function, persons with high levels of harm avoidance were nearly three times as likely to report mobility limitations as persons with low levels, and these effects largely reflected fatigability and fear of uncertainty. The association of harm avoidance with disability was not explained or modified by frailty, physical activity, depressive symptoms, neuroticism, extraversion, or cognition. The results suggest that harm avoidance is associated with disability in old age.

Activities of Daily Living↗

PubMedDate not supplied

Parkinsonian signs and functional disability in old age.

Little is known about the association between parkinsonian signs and functional disability. The authors examined the associations between four parkinsonian signs (gait, rigidity, bradykinesia, tremor) and the ability to perform physical and instrumental activities of daily living, in a large cohort of older Rush Memory and Aging Project participants who were free of dementia, Parkinson's disease, and antipsychotic drug use. In a series of logistic regression equations that controlled for age, sex, education, depressive symptoms, cognitive ability, chronic medical conditions, and psychotropic drug use, higher levels of parkinsonian signs were associated with higher levels of disability in performing both physical and instrumental activities of daily living.

Activities of Daily Living↗

PubMedDate not supplied

Correlates of life space in a volunteer cohort of older adults.

The authors measured the spatial extent of movement of older persons (i.e., life space) and examined factors that are related to life space. A larger life space was positively correlated with self-report measures of disability. In generalized logit models adjusted for demographics and time of year, a larger life space was associated with less visual impairment, higher levels of lower extremity motor performance, global cognition, and social involvement, and with personality and purpose in life. The results suggest that the range of environmental movement in older adults is a useful indicator of health in old age and may complement measures of disability.

Activities of Daily Living↗

PubMedDate not supplied

The relation of lifetime cognitive activity and lifetime access to resources to late-life cognitive function in older African Americans.

Research in older Caucasians has demonstrated that cognitive activity is related to cognitive function in late adulthood. Knowledge of this association is limited in older minority populations. We examined the relation of cognitive activity and access to cognitive resources, with cognitive function in a group of 108 older African Americans. We constructed two scales to measure the frequency of cognitive activity and the presence of resources that promote cognitive activity during early and late life. Both measures had high internal consistency and the cognitive activity scale had adequate temporal stability over a 4-week interval. In analyses that controlled for age and education, more frequent lifetime cognitive activity was related to current cognitive function, but lifetime cognitive resources only approached significance. The results suggest that both measures are psychometrically sound in a minority population and that lifetime cognitive activity may contribute to current cognitive function in African Americans.

Black or African American↗

PubMedDate not supplied

Postmortem indices linking risk factors to cognition: results from the Religious Order Study and the Memory and Aging Project.

We present data from the Religious Orders Study and the Memory and Aging Project linking risk factors to pathology and cognitive function. Both studies involve more than 1000 older persons who agreed to annual clinical evaluation and brain donation at death. Published findings from the studies to date suggest that the relationship between risk factors, pathology, and cognitive impairment is complex. In some cases, known neuropathologic indices mediate the association of risk factors to cognition. In other cases, risk factors modify the relation of pathology to cognition. Finally, some risk factors seem to be related to clinical Alzheimer disease and cognitive decline, even decline in episodic memory, in the absence of any association with amyloid plaques, neurofibrillary tangles, or other pathologic indices that can be identified and quantified at this time. The findings to date illustrate the kinds of insights that can be gained into mechanisms of disease through the incorporation of pathologic indices into well-designed, epidemiologic studies of aging and Alzheimer disease.

Aged↗

PubMedDate not supplied

ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials.

BACKGROUND: In primary prevention trials for Alzheimer disease, the inception cohort typically has normal or minimally impaired complex activities of daily living (ADL). ADL change during a trial could trigger detailed evaluation or serve as an outcome measure. A brief, easily administered, and reliable ADL rating scale would assist prevention studies. OBJECTIVES: To develop an ADL scale for prevention trials that allows self-rating or completion by informants. METHODS: The Activities of Daily Living-Prevention Instrument (ADL-PI) was developed, comprising 15 ADL and 5 physical function questions. Six hundred forty-four elderly subjects participating in the Prevention Instrument Project completed a self-rated version of the ADL-PI, and informants for 632 subjects completed an informant version. Informants also completed a Mild Cognitive Impairment (MCI) ADL questionnaire to allow comparisons. RESULTS: Subjects performed well on all ADL scales at baseline. Completion of the ADL-PI questionnaires at home or in-clinic yielded comparable information. Scores from baseline to 3 months had good reliability. The ADL-PI, obtained from either self-report or informants, discriminated between subjects rated as CDR 0 and CDR 0.5. Subjects with worse baseline cognitive performance also had slightly worse ADL-PI scores. Preliminary analysis indicates that subjects who triggered cognitive evaluations had slightly lower baseline ADL-PI scores by both self and informant reports. CONCLUSIONS: The ADL-PI can be completed at home or in clinic, and has adequate reliability. The utility of self-administered and informant versions and predictive value of reported deficits requires further follow-up.

Activities of Daily Living↗

PubMedDate not supplied

Association between blood pressure and cognitive function in a biracial community population of older persons.

We examined whether or not blood pressure is related to cognitive function in a cross-sectional study of a biracial community of 5,816 persons aged 65 years and older. Blood pressure had a curvilinear association with cognitive performance in linear regression models adjusted for age, sex, race and education. Scores were lower by 2-5 percentiles at 100 mm Hg systolic pressure compared to scores at the mean of 140 mm Hg and lower by <1 percentile at 180 mm Hg. For diastolic pressure, scores were lower by 2-3 percentiles at 60 mm Hg and by 1-2 percentiles at 100 mm Hg compared to scores at the mean (77 mm Hg). The differences in the scores with low blood pressure were reduced with further adjustment for body mass index, self-perceived health status, depressive symptoms, alcohol use and smoking. The curvilinear associations were stronger among persons with histories of stroke, myocardial infarction and hypertension. The cross-sectional association between blood pressure and cognitive functions is small and curvilinear and more apparent in persons with cardiovascular conditions.

Black or African American↗

PubMedDate not supplied

Cerebral infarctions and the relationship of depression symptoms to level of cognitive functioning in older persons.

OBJECTIVE: Recent studies report an association between depressive symptoms and cognitive impairment in old age. The neurobiologic basis of this association is unknown. The authors examined whether cerebral infarcts (present in 55 persons) accounted for the association of depressive symptoms with cognitive impairment in a group of 153 older Catholic nuns, priests, and brothers (67 with dementia and 86 without dementia). METHODS: Subjects underwent detailed clinical evaluations and brain autopsy at death. RESULTS: Mean values for depressive symptoms during the time of participation were associated with level of cognitive functioning proximate to death in analyses that controlled for age, sex, education, and Alzheimer disease (AD) pathology. The association of depressive symptoms with cognitive functioning was essentially unchanged after controlling for cerebral infarctions, which suggests that depressive symptoms, cerebral infarctions, and AD pathology were independently related to cognitive function. Similar results were found in analyses with episodic memory, semantic memory, working memory, perceptual speed, and visual-spatial ability. The results did not change in analyses examining the volume or location of cerebral infarctions. CONCLUSIONS: These data suggest that cerebral infarctions do not account for the association of depressive symptoms with level of cognitive functioning. The neurobiologic basis for this association remains to be elucidated.

Aged↗