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

Abstract

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...

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

“…All study researchers underwent online training and were certified as "CDR raters" [20] before scoring the CDR based on all information available from the baseline assessments. In accordance with other studies assessing progression in dementia with CDR-SB [6,8], patients who had an increase of less than 1 point in the CDR-SB score per year of follow-up were regarded as slow progressors.…”

“…A population-based study found that 30-58% of the participants with AD declined slowly, with a yearly change of less than one point on the CDR-SB and the MMSE [6]. Consistent with this finding, two memory clinic studies found that 25-30% of the patients were stable over a period of two to three years [5,8].…”

“…A mean yearly change in CDR-SB between 1.4 and 2.3 points is reported for patients with AD. Disease progression in AD is generally described as slower in the initial stages than in a more advanced stage of the disease, with yearly progression in CDR-SB of 0.5 to 1.9 points among patients with amnestic MCI (aMCI) or very mild dementia (CDR 0.5) and 1.3 to 1.9 points among patients with mild dementia (CDR 1) [3][4][5][6]. There is considerable individual variation in progression rates [7,8].…”

“…There is considerable individual variation in progression rates [7,8]. Using the Mini-Mental State Examination (MMSE) to measure cognition, the average loss is between 1.5 and 2.3 points per year [5,6,8,9]. A rapid cognitive decline, defined as a decrease of 3 to 5 points per year on the MMSE [8], has been shown in 10-30% of AD cases, depending on the threshold set and the population studied [8,10].…”

Cognitive reserve and the severity of Alzheimer’s disease

“…Tschanz et al 8 found that a significant proportion of persons with AD progresses slowly and suggest ongoing need to identify factors that may slow the progression of AD. Other studies have noted faster rates of progression in high CR patients after the diagnosis of AD 3,9,10 .…”