The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed. (JINS, 2014, 20, 1–12)

Background: Several follow-up [18F]fluorodeoxy glucose (FDG)-positron emission tomography (PET) studies have been performed in patients with mild cognitive impairment, but none have examined subjects with a Clinical Dementia Rating (CDR) of 0.5. Therefore, we used FDG-PET to investigate whether baseline glucose metabolism (CMRglc) in CDR 0.5 converters to dementia showed changes consistent with early Alzheimer's disease (AD).

Methods: Based on our earlier study, which we refer to as Prevalence Study 1998, we were able to examine 14 CDR 0, 42 CDR 0.5, and 12 AD subjects with PET and follow these subjects for five years. Baseline neuropsychological and CMRglc values were compared among groups of CDR 0, CDR 0.5/converters, CDR 0.5/non-converters, and AD subjects.

Results: All CDR 0 subjects were reassessed as CDR 0 after the five-year period. For CDR 0.5 subjects, 20 had converted to AD and 22 remained as CDR 0.5. In cognitive tests, CDR 0.5/converters showed significantly deteriorated recent memory function compared with CDR 0.5/non-converters at the baseline evaluation. Most brain areas showed decreased CMRglc in AD patients. CDR 0.5/converters had a significantly lower baseline CMRglc in the right cingulate, left inferior parietal and left temporal gyrus compared with CDR 0.5/non-converters.

Conclusions: Our findings suggest that CDR 0.5/converters have a baseline metabolic decline in areas that might be specific to AD.