Introduction. The aim of the study was to investigate whether the preclinical stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this end we investigated whether subjects with preclinical AD could be differentiated from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. Methods. Twenty-three subjects with preclinical AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects with very mild AD-type dementia were selected from a memory clinic population. Variables that were used to differentiate the groups were demographic variables, the Mini-Mental State Examination score, performance on cognitive tests, measures of functional impairment, and measures of noncognitive symptomatology. Results. Age and the scores for the delayed recall task could best discriminate between subjects with preclinical AD and subjects with nonprogressive mild cognitive impairment. The overall accuracy was 87% The score on the Global Deterioration Scale and a measure of intelligence could best discriminate between subjects with preclinical AD and subjects with very mild AD-type dementia. The overall accuracy was 85% Conclusions. Subjects with preclinical AD can be distinguished from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. This means that preclinical AD is a diagnostic entity for which clinical criteria should be developed.

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

Normals (N = 42) and patients with mild memory difficulty (N = 123) were given a neuropsychological test battery, and then followed annually for 3 years to determine which individuals developed sufficient functional change that they met clinical criteria for AD. Twenty-three of the 123 participants with mild memory difficulty converted to a diagnosis of probable Alzheimer's disease (AD) within 3 years of follow-up. Four of the 20 neuropsychological measures obtained at baseline, were useful in discriminating the groups on the basis of their status 3 years after the tests were given. The 4 discriminating tests pertained to assessments of memory and executive function. When the controls were compared to the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 89%, based on the neuropsychological measures at baseline. The discrimination of the controls from the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the Questionables) was 74% and the discrimination of the questionables from the converters was 80%. The specific tests that contributed to these discriminations, in conjunction with recent neuropathological and neuroimaging data from preclinical cases, have implications for which brain regions may be affected during the prodromal phase of AD. (JINS, 2001, 7, 631–639.)