Methods

Demographic and diagnostic information as well as neuropsychological and functional data from commonly used instruments were submitted electronically and merged into a central database. The data were previously collected at the 16 participating Alzheimer's Disease Centers on subjects enrolled from the community or referred for evaluation in projects studying normal aging and/or MCI. Demographic information included subjects' age, gender, ethnicity, education and marital status. Family history of AD and apoE-e4 allele status were also included. Diagnostic information generally reflected the outcome of a clinical evaluation conducted every one to two years that concluded with each subject being given a diagnosis of normal cognition, MCI, AD, or another type of dementia. Specific test data that were collected spanned multiple cognitive and functional domains and included tests of:

1. General mental status: Mini-Mental State Examination (MMSE; Folstein et al., 1975), Blessed-Roth Information-Memory-Concentration Test (Blessed et al., 1968), Mattis Dementia Rating Scale (Mattis, 1976)

2. Attention: Digit Span (WAIS-R) (Wechsler, 1981), Digit Symbol Substitution Test (Wechsler, 1981)

3. Memory: CERAD Word-List Learning Test (Morris et al., 1989; Welsh et al., 1991), Logical Memory subtest (WMS or WMS-R) (Wechsler, 1987), Visual Reproduction subtest (WMS or WMS-R) (Troester et al., 1993; Wechsler, 1987), Rey Auditory-Verbal Learning Test (Lezak, 1995)

4. Language: Boston Naming Test (Kaplan et al., 1983), Category Fluency Test (Benton and Hamsher, 1976; Morris et al., 1989), Letter Fluency Test (Goodglass and Kaplan, 1983; Newcombe, 1969)

5. Visuoperceptual, visuospatial, and visuoconstructive ability: Clock Drawing Test (Brodaty and Moore, 1997), Block Design subtest (Wechsler, 1987)

6. Problem solving, conceptualization, and executive functions: Trail-Making Test (Parts A and B) (Armitage, 1946; Reitan, 1958)

7. Functional measures: Clinical Dementia Rating (CDR) and the CDR Sum of Boxes (Morris, 1993), Blessed Dementia Scale (Blessed et al., 1968), Pfeffer Functional Activities Questionnaire (Pfeffer et al., 1982).

We are presently collecting additional measures including the Free and Cued Selective Reminding Test (FCSR) (Grober et al., 1997), the Hopkins Verbal Learning Test (Brandt, 1991), the Physical Self-Maintenance Scale (Lawton and Brody, 1969; Lawton, 1988), the Geriatric Depression Scale (Yesavage et al., 1982), and the Neuropsychiatry Inventory (Cummings et al., 1994).

Survival analysis was used to determine the conversion rates for normal subjects to MCI and AD. This methodology was utilized because it properly accounts for varying lengths of observation. The subjects in this study were enrolled at different times and had unequal lengths of follow-up. For each individual the length of follow-up or time to a clinical diagnosis of MCI or AD was ascertained and Kaplan-Meier survival curves (Kaplan and Meier, 1958) were generated.

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