Alzheimer’s disease brain atrophy subtypes are associated with incident dementia in subjective cognitive complaint and mild cognitive impairment

Abstract

AbstractBackgroundAlzheimer’s disease (AD) brain atrophy subtypes on structural MRI have been associated with rate of cognitive decline in AD and prodromal AD. However, previous works were based on selected amyloid‐positive and/or cognitively‐impaired patients. The clinical relevance of brain atrophy subtypes categorization in people referred to Memory Clinics for subjective cognitive complaint (SCC) or mild cognitive impairment (MCI), without any a priori assumptions regarding their amyloid status, is currently unknown.MethodsWe investigated 2118 subjects from the French Memento cohort presenting either with SCC or MCI and for whom both hippocampal and cortical volumes were available at baseline. Among them, 883 also had Amyloid‐PET and/or CSF biomarkers. They were prospectively followed during 4 years for dementia status and neuropsychological performances. MRI scans at baseline were used to define groups with “limbic predominant atrophy”, “hippocampal sparing atrophy”, “typical/diffuse atrophy” and “no evidence of brain atrophy”, based on previously described algorithms.ResultsIn Cox proportional‐hazards models, “typical/diffuse atrophy” and “limbic predominant atrophy” were associated with an increased risk of developing dementia over time (HR=3.67; 95%CI 2.63–5.13 and HR=1.77; 95%CI 1.05–2.98 respectively), independently of age, gender, educational level, ApoE4 genotype and CDR‐SB at baseline. Brain atrophy subtypes categorization was more informative than hippocampal and/or cortical volumes separately, when comparing Akaike information criteria of Cox models. Very similar results were found when analyses were restricted to the sample of amyloid‐positive participants (n=236) (HR=3.69; 95%CI 2.03–6.70 for “typical/diffuse atrophy” and HR=2.40; 95%CI 0.96–5.96 for “limbic predominant atrophy”).ConclusionAD brain atrophy subtypes are associated with conversion to dementia in patients with SCC or MCI consulting in Memory Clinics, agnostic of any a priori assumptions regarding their amyloid status. Because this categorization based on structural MRI is more informative than hippocampal and/or cortical volumes, it could be widely used as a biomarker in future epidemiological and clinical studies.