Neuropathological Validation of the Alzheimer’s Questionnaire

Background The Alzheimer’s Questionnaire (AQ) is a brief, informant‐based screening tool that has demonstrated good diagnostic accuracy in identifying clinical Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). The AQ has been further validated by its correlations with established informant‐ and performance‐based cognitive assessments as well as with standard neuropsychological tests. Recent evidence has also demonstrated that the AQ correlates well with PET‐based measures of amyloid plaque. The aim of this study is to validate the AQ with the hallmark neuritic plaque (NP) and neurofibrillary tangle (NFT) pathology of AD. Method Data from 205 prospectively‐followed autopsy cases classified as AD (n=90), aMCI (n=42), or cognitively unimpaired (CU, n=73) were used in this analysis. The average age at death was 87.07±7.84 years with the average interval between the last clinical assessment and death of 16.48±14.32 months. Semi‐quantitative measures of NP and NFT pathology from five brain regions were used to assess total plaque and total tangle loads which were then correlated with the AQ, Clinical Dementia Rating Sum of Boxes (CDR‐SOB), and the Mini‐Mental State Exam (MMSE). Spearman correlations were used in the primary analyses and were followed up with robust regression models that adjusted for age at death, sex, education, and APOE ε4 carrier status. Result The AQ correlated significantly with NP load (r=0.37, p<0.001) and NFT load (r=0.57, p<0.001). These associations remained significant after covariate adjustment (NP: β=0.28, 95% CI: (0.21, 0.34), p<0.001; NFT: β=0.22, 95% CI: (0.17, 0.28), p<0.001). The MMSE and CDR‐SOB showed similar correlations with NP load (r=‐0.37, r=0.35, respectively) and NFT load (r=‐0.58, r=0.55, respectively). Conclusion These findings extend previous clinical and neuroimaging findings of the AQ showing that it correlates well with the hallmark NP and NFT pathology of AD and provide additional confidence to clinicians who use the AQ to screen for AD‐related cognitive impairment.