Accumulating evidence suggests that subjective cognitive complaints (SCC) may indicate subtle cognitive decline characteristic of individuals with preclinical Alzheimer’s disease (AD). In this study, we sought to build upon previous studies by associating SCC and amyloid-β deposition using Positron Emission Tomography with Pittsburg Compound B (PiB-PET) in cognitively normal older individuals. One-hundred thirty one subjects (mean age 73.5 ± 6) were administered three subjective cognitive questionnaires and a brief neuropsychological battery. A relationship between a subjective memory complaints composite score and cortical PiB binding was found to be significant, even after controlling for depressive symptoms. By contrast, there were no significant relationships between objective cognitive measures of memory and executive functions and cortical PiB binding. Our study suggests that SCC may be an early indicator of AD pathology detectable prior to significant objective impairment.

ObjectiveBoth amyloid-β (Aβ) deposition and brain atrophy are associated with Alzheimer's disease (AD) and the disease process likely begins many years before symptoms appear. We sought to determine whether clinically normal (CN) older individuals with Aβ deposition revealed by positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) also have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD.MethodsA total of 119 older individuals (87 CN subjects and 32 patients with mild AD) underwent PiB PET and high-resolution structural magnetic resonance imaging (MRI). Regression models were used to relate PiB retention to cortical thickness and hippocampal volume.ResultsWe found that PiB retention in CN subjects was (1) age-related and (2) associated with cortical thickness reductions, particularly in parietal and posterior cingulate regions extending into the precuneus, in a pattern similar to that observed in mild AD. Hippocampal volume reduction was variably related to Aβ deposition.InterpretationWe conclude that Aβ deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment. ANN NEUROL 2010;

Cerebral amyloid beta (Aβ) deposition occurs in a substantial fraction of cognitively normal (CN) older individuals. However, it has been difficult to reliably detect evidence of amyloid-related cognitive alterations in CN using standard neuropsychological measures. We sought to determine whether a highly demanding face-name associative memory exam (FNAME) could detect evidence of Aβ-related memory impairment in CN. We studied 45 CN subjects (mean age = 71.7 ± 8.8) with Clinical Dementia Rating (CDR) scores = 0 and MMSE ≥ 28, using Positron Emission Tomography with Pittsburgh Compound B (PiB PET). Memory factor scores were derived from a principal components analysis for FNAME name retrieval (FN-N), FNAME occupation retrieval (FN-O) and the 6-Trial Selective Reminding Test (SRT). Using multiple linear and logistic regression analyses, we related the memory factor scores to PiB distribution volume ratios (DVR, cerebellar reference) as either a continuous or a dichotomous variable in frontal cortex and a posterior cortical region representing the precuneus, posterior cingulate and lateral parietal cortices (PPCLP), co-varying for age and AMNART IQ (a proxy of cognitive reserve (CR)). A significant inverse relationship for FN-N was found with Aβ deposition in frontal (R2 = .29, β = −2.2, p = 0.02) and PPCLP cortices (R2 = .26, β = −2.4, p = 0.05). In contrast, neither FN-O nor the SRT were significantly related to Aβ deposition. Performance on a demanding test of face-name associative memory was related to Aβ burden in brain regions associated with memory systems. Associative memory for faces and names, a common complaint among older adults, may be a sensitive marker of early Aβ-related impairment.