Objectives-Progression of Alzheimer's dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains. Design-Longitudinal, prospective cohort study Setting-Cache County (Utah)Participants-328 persons diagnosed with Possible/Probable AD Measurements-Mini-Mental State Exam (MMSE), Clinical Dementia Rating sum-of-boxes (CDR-sb), and Neuropsychiatric Inventory (NPI).Results-Over a mean follow-up of 3.80 (range 0.07-12.90) years, the mean (S.D.) annual rates of change were −1.53 (2.69) on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) scale points on the NPI. Among surviving participants, 30-58% progressed less than one point/year on these measures, even 5-7 years after dementia onset. Rates of change were correlated between MMSE and CDR-sb (r=−0.62, df=201, p<0.001) and between the CDR-sb and NPI (r=0.20, df=206, p<0.004). Females (LR χ 2 =8.7, df=2, p=0.013) and those with younger onset (LR χ 2 =5.7, df=2, p=0.058) declined faster on the MMSE. Although one or more APOE ε4 alleles and ever-use of FDA-approved anti-dementia medications were associated with initial MMSE scores, neither was related to the rate of progression in any domain.Conclusions-A significant proportion of persons with AD progresses slowly. The results underscore differences between population-vs. clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD. KeywordsAlzheimer's disease; dementia; cognition; neuropsychiatric symptoms; progression; decline Alzheimer's dementia (AD) is a significant cause of disability and mortality among the elderly. Some 26.6 million cases presently worldwide may increase to 106.2 million by 2050,(1) unless a means of prevention can be identified. Without a cure, better understanding of the clinical course and course-modifying factors is needed.AD causes impairment not only in cognition and function, but also in behavior prompted by neuropsychiatric symptoms (NPS). Numerous studies report significant variability in the rate of cognitive and functional decline in AD. For example, a recent review reported that the mean annual rate of change (ARC) on the Mini-Mental State Exam (MMSE), a global measure of cognition, varied from 0.8 to 4.4 points.(2) Similar variability is seen in functional decline,(3) although comparisons across studies are impeded by differences in instrumentation. NPS in AD are marked by increasing incidence over time and by an episodic course. (4) These studies of the natural history of AD share several limitations. Most come from observations in clinics or clinical research centers. Compared to panels of AD cases ascertained from populations, clinic AD patients are up to 20 years younger, have higher Here, we d...

Active involvement in cognitively stimulating pursuits may be beneficial for persons with AD.

Objective-To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD).Methods-The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or CABG, and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status.Results-One or more NPS were observed in 51.0% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR=4.76, p=0.02), depression (OR=3.87, p=0.03), and apathy (OR=4.48, p=0.02). Hypertension was associated with increased risk of delusions (OR=2.34, p=0.02), anxiety (OR=4.10, p=0.002), and agitation/aggression (OR=2.82, p=0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health. Conclusions-Resultssuggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in CORRESPONDING AUTHOR:

There are several population-based studies of aging, memory, and dementia being conducted worldwide. Of these, the Cache County Study on Memory, Health and Aging is noteworthy for its large number of "oldest-old" members. This study, which has been following an initial cohort of 5,092 seniors since 1995, has reported among its major findings the role of the Apolipoprotein E gene on modifying the risk for Alzheimer's disease (AD) in males and females and identifying pharmacologic compounds that may act to reduce AD risk. This article summarizes the major findings of the Cache County study to date, describes ongoing investigations, and reports preliminary analyses on the outcome of the oldest-old in this population, the subgroup of participants who were over age 84 at the study's inception.

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