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Progression of Cognitive, Functional, and Neuropsychiatric Symptom Domains in a Population Cohort With Alzheimer Dementia: The Cache County Dementia Progression Study

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Objectives

Progression of Alzheimer 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

Three hundred twenty-eight persons with a diagnosis of 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 (SD) annual rates of change were −1.53 (2.69) scale points on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) on the NPI. Among surviving participants, 30% to 58% progressed less than 1 point per year on these measures, even 5 to 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). Female subjects (LR χ2 = 8.7, df = 2, p = 0.013) and those with younger onset (likelihood ratio [LR] χ2 = 5.7, df = 2, p = 0.058) declined faster on the MMSE. Although one or more apolipoprotein E η 4 alleles and ever use of FDA-approved antidementia 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-based versus clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD.

Section snippets

METHODS

The DPS was derived from the longitudinal, population-based Cache County Study on Memory in Aging (CCSMA), which has examined the prevalence, incidence, and risk factors for dementia in a U.S. county recognized for its residents' longevity.13 In its first wave, CCSMA enrolled 90% of the 5,677 county residents who were 65 years or older. Three subsequent triennial waves of case detection have been completed. As described later, most individuals with incident dementia have been followed

RESULTS

The CCSMA identified 328 individuals with incident AD. The majority of the participants were female (66%) and White (99%). Table 1 displays sample characteristics at the diagnosis visit. Participants were observed at times between 0.07 and 12.9 years after onset. Sixty-three percent died while being followed, and 4% either refused further participation or moved out of the area. The remaining 33% were active participants at the time of analysis. The mean (SD) duration of dementia from onset to

DISCUSSION

This study of a population-based, incident cohort of persons with AD found the following observations: first, that 30% to 58% of those who survived 5 to 7 years after dementia onset declined slowly; second, that AD progressed faster in women than in men; third, that number and severity of NPS increased over time but the course was variable and episodic; and fourth, that rate of change in NPS was correlated weakly, if at all, with rate of change in cognition or function.

Several studies have

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  • Authors disclosure: Peter V. Rabins: Legal testimony for Janssen Pharmaceutical; Martin Steinberg: Grant support from NIA and Elan Pharmaceuticals; Kathleen A. Welsh-Bohmer: 1) Scientific advisory board for Medivation, Inc. 2) Received funding for travel and speaker honoraria from Medivation, Inc., and Elan Corporation/Wyeth. 3) Has served/serves as an associate editor of Neuropsychology Review, on the editorial boards of Alzheimer's & Dementia, the Journal International Neuropsychological Society, and the Journal of Experimental and Clinical Neuropsychology, and as a consulting editor for Aging, Neuropsychology, and Cognition and Neuropsychology. 4) Holds US Patent #6867236 (issued 2005): Nonsteroidal Anti-inflammatory drugs for the treatment of Alzheimer's disease. 5) Receives royalties from the publication of Geriatric Neuropsychology: Assessment and Intervention (Guildford Publications, 2006). 6) Receives research support from the NIH (NIA AG11380 [PI] and NIA AG028377 [PI]); Constantine Lyketsos: 1) Grant support (research or CME)—NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis. 2) Consultant/Advisor—Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Genentech. 3) Honorarium or travel support—Pfizer, Forest, Glaxo-Smith Kline, Health Monitor; JoAnn Tschanz, Chris Corcoran, Sarah Schwartz, Katherine Treiber, Robert Green, Maria Norton, Michelle Mielke, Kathleen Piercy, Jeanne-Marie Leoutsakos, and John C.S. Breitner have no disclosures.

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