Operationalizing diagnostic criteria for Alzheimer's disease and other age-related cognitive impairment-Part 2

Abstract

This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment and/or dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor determining prevalence estimates of Alzheimer's disease (AD) is the severity of cognitive impairment used as a threshold to define cases. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than the studies aimed at identifying persons in the earliest stages of AD. There are limited autopsy data from the aforementioned epidemiological studies to address accuracy in the diagnosis of etiological subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment and also some persons without dementia or mild cognitive impairment meet pathological criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies.

Fig. 1

Comparing varying estimates of the prevalence of dementia based on requiring different levels of severity (mild or moderate) to diagnose clinical dementia: Persons aged 65 years or older from the Framingham Heart Study cohorts: 1990 to 2008. [Note: this is not a point or a period prevalence, but a prevalence estimated by assigning each cohort member a status as demented or not on the day they turned a given age (indicated on the x-axis).]

Fig. 2

Schematic representation of the distribution of Alzheimer’s disease (AD) in a population. 2A is realistic, 2B is not. As shown in 2C and 2D, minor differences in where the cut point is placed can strongly affect the resulting estimates of AD prevalence.

Fig. 3

The relative proportion of subjects classified as having dementia and MCI in the Mayo Clinic Study of Aging. Panel A demonstrates the current division between MCI and dementia as determined by a consensus conference. The composite cognitive z score is minus 2.4. Panels B, C, and D demonstrate the relative changes in proportions of cases with MCI and dementia as the degree of cognitive impairment moves toward the milder end of the spectrum.

Fig. 4

A hypothetical threshold for differentiating mild cognitive impairment (MCI) from Alzheimer’s disease (AD). Arrow A represents the older studies of prevalence of AD. Arrow B represents more recent studies but still characterizing fully developed dementia. Arrows C and D would result from the criteria for AD being moved into the current MCI range (see text).

Fig. 5

Participant flow chart for the diagnosis of dementia in the Baltimore Longitudinal Study of Aging from 1985 to 1998 [30]. Abbreviations: IMC, Information Memory Concentration.

Fig. 6

Age-specific incidence rates of Alzheimer’s disease on a log scale from 4 US studies: Framingham, MA, East Boston, MA, Rochester, MN, and Baltimore, MD [43]. Reproduced with permission.

Fig. 7

Neuropsychological scores for Baltimore Longitudinal Study of Aging participants by clinical diagnosis group. Box width varies with sample size. Abbreviations: CSR, Cued Selective Reminding; CIND, cognitive impairment not dementia; MMSE, Mini-Mental State Examination.