Epidemiology of Alzheimer Disease

The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease

Progression of extrapyramidal signs in Alzheimer's disease. clinical and neuropathological correlates

Extrapyramidal signs (EPS) are frequent in Alzheimer's disease (AD) and core manifestation of related diseases, i.e., dementia with Lewy bodies and Parkinson's disease; furthermore, Lewy bodies and AD-type pathology occur in all three conditions

Subtle Extrapyramidal Signs and Incident Dementia: A Follow-up Analysis

We previously reported [1] that the presence of mild extrapyramidal signs (EPS) significantly predicts Alzheimer's disease (AD) in elderly individuals, independent of age, education, or gender. We now report a confirmation of our data after accrual of more cases and additional follow-up assessments

Heterogeneity and Prognosis in Dementia of the Alzheimer Type

The diagnosis of dementia of the Alzheimer type (DAT) depends on the clinician's ability to document intellectual impairment in the patient and to exclude other causes of dementia. About 50% of all demented patients entering a hospital are ultimately found at postmortem examination to have Alzheimer's disease. However, using the most rigorous criteria the accuracy of correct clinical diagnosis at autopsy approaches only 80-90% and this excludes some unusual patients. Most investigators use the Diagnostic and Statistical Manual of Mental Disorder-third ed. (DSM-III) criteria for dementia, a rating of performance in activities of daily living, and an assessment of personality and intellectual function for diagnosis. Two clinical rating scales: the Blessed Dementia Rating Scale (parts 1 and 2) and the Clinical Dementia Rating Scale, are used frequently and seem to identify patients with DAT with greater accuracy than other scales

Comparison of Cognitive Changes in Patients with Alzheimer's and Parkinson's Disease

Objective. —To compare cognitive changes in the dementias of Parkinson's disease (PD) and Alzheimer's disease (AD). Design. —Case series, group comparisons. Setting. —Ambulatory care referral center. Patients. —Consecutive sample of 14 patients with PD dementia and 27 with probable AD matched for overall intellectual function using a mental status test, as well as 1 nondemented PD and 12 mild probable AD patients, similarly matched for overall intellectual function. All demented patients met Diagnostic and Statistical Manual, Revised Third Edition, criteria for dementia. Main Outcome Measures. —Performance on a battery of neuropsychological tests assessing verbal and nonverbal memory, verbal fluency, and constructional ability. Results. —Nondemented and demented patients with PD performed worse than their probable AD comparison groups on verbal fluency and visuospatial tasks. Cognitive changes attributable to dementia were similar in PD and probable AD but were not identical. The patients with probable AD demonstrated more marked change in memory performance with delay. Conclusions. —Our findings suggest that when dementia occurs in PD it is overlaid on cognitive changes that already exist in nondemented patients but that the dementing process in PD involves systems other than those responsible for cognitive change in nondemented PD patients. We hypothesize that in most cases, dementia in PD involves changes in a nondopaminergic neurotransmitter system but is not due to concomitant AD

Prism Adaptation in Parkinson's Disease

Prism adaptation is impaired by lesions in the basal ganglia in non-human primates, suggesting that this area is involved in this form of visuomotor learning. We investigated the ability of patients with Parkinson's disease to prism adapt. Patients and controls wore prisms which deflected vision laterally by 11 degrees. After baseline testing with a localisation task that permitted no feedback about performance accuracy, prism adaptation was tested at 4 minute intervals over a 28 minute trial. All subjects erred initially, reaching too far to the left of the target, but a separate pointing task encouraged adaptation and reaching error decreased at a similar rate in Parkinsonians and controls. Immediately after the prisms were removed, all subjects reached to the right of the target. This negative after effect was present in controls but not patients when assessed 4 minutes later, suggesting that the patients could not maintain the new sensorimotor relationship imposed by the prisms after their removal. This is similar to performance on visuospatial and executive tasks in Parkinsonians, where ongoing behaviour cannot be modulated without external guidance

Selective Decline in Memory Function among Healthy Elderly

Objective: To use longitudinally acquired data to establish whether aging is associated with memory decline. Background: Memory loss is one of the most frequent complaints among the elderly. Nevertheless, age-related memory decline remains controversial in large part because it has been established with cross-sectional studies. Methods: A total of 212 community-based healthy people were followed prospectively and evaluated annually with a neuropsychological battery testing memory and other cognitive domains. To control for the learning effect—the improvement in test performance associated with repeated exposure—longitudinal performance was compared between two age groups. Results: The older age group displayed a relative decline in memory performance with time. In contrast to memory, a relative age-related decline was not observed in tests of language, visuospatial ability, and abstract reasoning. Furthermore, within the memory domain, age-related decline was restricted to a specific aspect of memory, manifesting only in a measure sensitive to the acquisition and early retrieval of new information, and not in a measure of memory retention. This profile of age-related cognitive decline anatomically localizes to the hippocampal formation. Conclusion: This study establishes age-related memory decline using longitudinal data, and shows that this decline does not occur diffusely across multiple cognitive domains. Both early AD as well as non-AD processes likely contribute to age-related memory decline, and continued follow-up may reveal distinguishing features between these two

Mediterranean Diet and Alzheimer Disease Mortality

BACKGROUND: We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. OBJECTIVES: To examine the association between MeDi and mortality in patients with AD. METHODS: A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. RESULTS: Eighty-five patients with AD (44%) died during the course of 4.4 (+/-3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years' longer survival), whereas subjects at the highest tertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years' longer survival; p for trend = 0.003). CONCLUSION: Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect

Cumulative Risks of Developing Extrapyramidal Signs, Psychosis, or Myoclonus in the Course of Alzheimer's Disease

Cumulative risks of developing extrapyramidal signs, psychosis, and myoclonus in the course of Alzheimer's disease (AD) were estimated in 72 patients with probable AD by the Kaplan-Meier survival method. The cumulative risk functions were found to increase at different rates for different signs as AD progressed. Comparisons of the cumulative risk functions revealed that in the early stages of AD, extrapyramidal signs and psychosis were more likely to develop than myoclonus. As AD progressed, the risk of developing myoclonus became as great as that of developing the other two signs. This study suggests that extrapyramidal signs, psychosis, and myoclonus represent developmental features that mark the progression of AD, rather than indicators of disease subtypes. The estimated cumulative risk functions set a reasonable expectation for the timing and likelihood of the emergence of the clinical signs. This, in turn, might aid in disease prognosis because the biological bases of these signs have been established and they have been shown to be predictive of other markers of disease course