Longitudinal subcortical volume changes and their correlations with multiple PET and fluid biomarkers in dominantly inherited Alzheimer disease.

ObjectiveTo investigate longitudinal subcortical structural changes in autosomal dominant Alzheimers disease in relation to multiple PET and fluid biomarkers. MethodsParticipants underwent structural MRI, 11C-Pittsburgh Compound B PET, 18F-fluorodeoxyglucose PET, and CSF and plasma assessments. Rates of biomarker change as a function of estimated years to symptom onset were estimated using multivariate linear mixed-effects models, and longitudinal associations between subcortical atrophy and multiple biomarkers were evaluated. ResultsA total of 601 participants completed one or more clinical evaluations, with up to eight annual visits. Mutation carriers showed significantly greater longitudinal atrophy in the left amygdala, bilateral thalamus, putamen, nucleus accumbens, and hippocampus compared with non-carriers (Bonferroni-corrected p < 0.05). The earliest divergence was observed 13.2 years before the expected symptom onset in the right nucleus accumbens, following amyloid-{beta} (A{beta}) accumulation in the right thalamus that began 23.8 years before onset. Among carriers, atrophy in the right thalamus, bilateral putamen, and bilateral nucleus accumbens was significantly associated with region-specific or cortical A{beta} accumulation, as well as with CSF A{beta}42, A{beta}42/A{beta}40 ratio, total tau, and phosphorylated tau (Bonferroni-corrected p < 0.05). ConclusionAs MRI is more cost-effective and time-efficient than PET, subcortical volume atrophy measured by MRI may serve as a practical biomarker for the early detection of Alzheimers disease.