David W. Gilley

Environmental factors and Parkinson's disease A case‐control study in China

We studied the role of environment in the development of Parkinsons disease (PD) in China, where industrialization is relatively recent and the population geographically stable. Using a case-control method, we investigated the relationship between PD and exposure to the following factors before disease onset: place of residence, source of drinking water, environmental and occupational exposure to various agricultural and industrial processes. Occupational or residential exposure to industrial chemicals, printing plants, or quarries was associated with an increased risk of developing PD. In contrast, living in villages and exposure to the common accompaniments of village life, wheat growing and pig raising, were associated with a decreased risk for PD. PD cases and controls did not differ with respect to other factors investigated. These findings are consistent with the hypothesis that environmental exposure to certain industrial chemicals may be related to the development of PD.

Environmental factors in the etiology of Parkinson's disease.

Parkinsons disease (PD) has been proposed to result from the interaction of aging and environment in susceptible individuals. Defective metabolism of debrisoquine, inherited as an autosomal recessive, has been associated with this susceptibility. In 35 PD patients and 19 age-matched controls, no significant differences in debrisoquine metabolism were found, although a trend to impaired metabolism was noted in patients with disease onset less than or equal to 40. Foci of PD patients were associated with rural living and well water drinking, or rural living coupled with market gardening or wood pulp mills. In a questionnaire survey, patients with PD onset less than or equal to age 47 were significantly more likely to have lived in rural areas and to have drunk well water than those with onset greater than or equal to age 54 (p less than or equal to 0.01). Because of population mobility in North America, a case-control study designed to test environmental, occupational, dietary and other proposed risk factors for PD was conducted in China, where the population is more stationary and the environment more stable. No significant differences in incidences of head trauma, smoking or childhood measles were found between patients and controls.

Person-specific paths of cognitive decline in Alzheimer's disease and their relation to age.

Change in global and specific measures of cognitive function was studied in a cohort of 410 persons with Alzheimers disease. Persons completed up to 5 annual evaluations; follow-up participation among survivors exceeded 90%. Average annual decline was 0.57 standard score units (95% confidence interval [CI]: -0.51 to -0.62) on a composite measure based on 17 individual tests and 3.26 points (95% CI: -3.06 to 3.46) on the Mini-Mental State Examination, but substantial heterogeneity was apparent. On both global and specific measures, rate of cognitive decline was reduced in older persons compared with younger persons. A similar effect was observed for estimated age of disease onset. The effect of age was approximately linear and was not attributable to education, sex, race, other conditions that impair cognition, or mortality. The results indicate that person-specific paths of cognitive decline in Alzheimers disease vary substantially and suggest that in clinical settings some of this variability is related to age.

Hallucinations, delusions, and cognitive decline in Alzheimer's disease

OBJECTIVES To examine the occurrence of hallucinations and delusions in Alzheimers disease over a 4 year period and their association with rate of cognitive decline. METHODS A cohort of 410 persons with clinically diagnosed Alzheimers disease underwent annual clinical evaluations over a 4 year period. Participation in follow up exceeded 90% in survivors. Evaluations included structured informant interview, from which the presence or absence of hallucinations and delusions was ascertained, and detailed testing of cognitive function. The primary cognitive outcome measure was a composite cognitive score based on 17 individual performance tests. The mini mental state examination (MMSE) and summary measures of memory, visuoconstruction, repetition, and naming were used in secondary analyses. RESULTS At baseline, hallucinations (present in 41%) and delusions (present in 55%) were common and associated with lower cognitive function. In analyses that controlled for baseline level of cognitive function, demographic variables, parkinsonism, and use of antipsychotic medications, hallucinations, but not delusions, were associated with more rapid cognitive decline on each cognitive measure. In the primary model, there was a 47% increase in the average annual rate of decline on a composite cognitive measure in those with baseline hallucinations compared with those without them. This effect was mainly due to a subgroup with both auditory and visual hallucinations. CONCLUSION These findings suggest that the presence of hallucinations is selectively associated with more rapid cognitive decline in Alzheimers disease.

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 Alzheimers 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.

Education and the course of cognitive decline in Alzheimer disease

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.

Psychotic symptoms and physically aggressive behavior in Alzheimer's disease

OBJECTIVE: To examine the relationship between psychotic symptoms and subsequent physically aggressive behavior in outpatients with Alzheimers disease.

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.

Use of the national adult reading test to estimate premorbid iq in dementia

Two methods for estimating premorbid IQ were employed in a sample of 199 dementia patients and 26 control subjects: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula-a demographically based estimate. The dementia sample consisted of probable Alzheimers disease, multi-inf arct dementia and a mixture of the two. Controls consisted of the spouses of the patient sample. The patient sample was divided into three levels of dementia severity equated for age and level of education. The NART estimates in the mild and moderate/severe dementia groups differed significantly from those for the very mildly demented patients and controls. The results suggest that the applicability of the NART in estimating premorbid IQ in dementia may be limited.

Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer's disease

We evaluated the change in density of total senile plaques, plaque subtypes, and neurofibrillary tangles, from biopsy to autopsy in left frontal cortical sections from four patients with clinically typical Alzheimers disease (AD). Comparisons were made on sections stained with modified Bielschowsky and Thioflavin S. In two cases, comparisons were also made on tissue stained with a monoclonal Alz-50 antibody and an antiserum to A beta (beta-amyloid protein). Despite a marked decline in mental status over several years of follow-up clinical evaluations, there was no consistent significant change in numerical density of plaques or tangles among the four cases. However, we did find fewer primitive plaques in the autopsy specimens. These results from longitudinally evaluated persons with typical AD suggest that although plaques and tangles may serve as adequate markers of the presence of AD, their numerical density within a single neocortical region may not reflect dementia severity. This conclusion supports the results of recent cross-sectional studies on the progression of pathology among persons with AD.