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.

Background/Aims: Neuropsychiatric symptoms in Alzheimer’s disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects. Methods: Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer’s Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years. Results: Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite. Conclusions: These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD.

Objectives To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment and mild AD dementia. Design Cross-sectional and longitudinal studies. Setting 57 research sites across North America. Participants 812 community dwelling volunteers; 413 participants in the CSF sub-study. Measurements Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau and phosphorylated tau derived from the Alzheimer’s Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in 7 regions, baseline CSF biomarkers and apathy and hallucinations at baseline and longitudinally. Covariates included diagnosis, gender, age, Apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration. Results Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, while reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses. Conclusions These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD.