Hippocampal subregional volume changes in elders classified using positron emission tomography‐based Alzheimer's biomarkers of β‐amyloid deposition and neurodegeneration

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of β‐amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11C]PIB‐PET to assess β‐amyloid aggregation (A+) and [18F]FDG‐PET to account for neurodegeneration ((N)+). Magnetic resonance imaging‐based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)− categories, subicular volumes were inversely correlated with the degree of Aβ deposition. The A−(N)+ subgroup showed reduced HSV relative to the A−(N)− subgroup also in the subiculum/presubiculum. Combining all (N)− subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A− classification (controlling for WMH load); these between‐group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)− categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)− subjects in direct proportion to the degree of Aβ deposition. The meaningful HSV reductions detected in the A−(N)+ subgroup highlights the strength of biomarker‐based classifications outside of the classical AD continuum. Volume of hippocampal subregions (presubiculum/subiculum) are reduced in elderly subjects presenting cortical β‐amyloid deposition and signs of neurodegeneration. In elderly subjects with no neurodegeneration, hippocampal subregional volumes are also reduced in those with cognitive decline (dementia or amnestic mild cognitive impairment) compared to cognitively intact individuals.