M. X. Tang

BACKGROUND: The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk. OBJECTIVE: To explore the association of the aggregation of vascular risk factors with AD. METHODS: The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD. RESULTS: Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other. CONCLUSIONS: The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.

OBJECTIVES: To estimate the frequency and determine the risk factors for incident dementia in community-dwelling patients with Parkinson's disease (PD) and in control subjects. DESIGN: Prospective cohort study. During a 3.5-year period, 140 patients with idiopathic PD without evidence of dementia and 572 nondemented control subjects were identified in the community of Washington Heights-Inwood in New York, NY. All subjects underwent neurological and neuropsychological evaluations and follow-up examinations. RESULTS: Twenty-seven patients with PD (19.2%) became demented throughout 2 years, as compared with 87 (15.2%) of the control subjects. The relative risk (RR) for the development of dementia with PD was 1.7 (95% confidence interval [CI], 1.1 to 2.7) after adjusting for age, education, and gender. Predictive features of incident dementia were an extrapyramidal score greater than 25 (RR, 3.56; 95% CI, 1.4 to 8.9) and a Hamilton Depression Rating Scale score greater than 10 (RR, 3.55; 95% CI, 1.6 to 7.9). CONCLUSION: Patients with PD, especially those with severe extrapyramidal signs, have almost twice the risk for the development of dementia than do community-dwelling control subjects.

BACKGROUND: Mild parkinsonian signs (MPS) are associated with prevalent and incident dementia but it is not known whether they are associated with mild cognitive impairment (MCI). OBJECTIVE: To determine whether MPS and specific MPS (changes in axial function, rigidity, tremor) are associated with MCI in nondemented community-dwelling older people in northern Manhattan, NY. METHODS: Participants underwent neurologic assessment, including a modified motor portion of the Unified Parkinson Disease Rating Scale. MCI was diagnosed in nondemented participants who had cognitive impairment based on neuropsychological testing and no functional impairment. Participants with MCI were classified as having MCI with memory impairment (MCI+M) vs MCI without memory impairment (MCI-M). RESULTS: MCI was present in 608 (27.3%) of 2,230 participants, including 255 participants with MCI+M and 353 with MCI-M; 1,622 participants did not have MCI. MPS were present in 369 (16.5%) of 2,230 participants. In a univariate logistic regression model, odds of MCI+M (vs no MCI) were 51% higher in participants with MPS compared to those with no MPS (OR = 1.51, 95% CI = 1.09 to 2.09, p = 0.01). Multivariate models yielded similar results (OR = 1.45, 95% CI = 1.03 to 2.05, p = 0.03). Rigidity was present in a higher proportion of participants with MCI+M compared to participants without MCI. CONCLUSIONS: Mild parkinsonian signs, especially rigidity, are associated with amnestic mild cognitive impairment. Mild parkinsonian signs and mild cognitive impairment may share similar pathogeneses. Whether this involves Alzheimer-type pathology, Lewy bodies, or vascular changes in the basal ganglia or basal ganglia circuitry deserves further investigation in postmortem studies.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.