Different levels of cognitive reserve among typical and limbic‐predominant hypometabolic subtypes of Alzheimer’s Disease

Abstract

AbstractBackgroundResidual approaches for estimating cognitive reserve (CR) are assumed to reflect relative resilience of individuals to neuropathological change in Alzheimer’s disease (AD). In the present study, we characterized differences in CR in people expressing distinct hypometabolic subtypes of AD‐related neurodegeneration.MethodWe analyzed MRI, FDG‐PET and cognitive performance data of Aβ‐positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, including 58 cognitively normal (CN), 217 prodromal AD and 177 AD dementia participants. Participants’ FDG‐PET scans were classified into the two principal hypometabolic subtypes of AD – typical and limbic‐predominant – as determined previously by a data‐driven clustering analysis. W‐scores were calculated as standardized residuals from a regression model with temporoparietal gray matter (GM) volume adjusted to total intracranial volume (TIV) as the dependent variable and with memory and executive function composite scores, as well as covariates age, gender, TIV and dementia status as independent variables (Fig. 1). The scores were multiplied by “‐1” so that higher values indicated lower than expected temporoparietal GM volume at a given level of cognitive performance and therefore represented higher CR. We evaluated the effects of W‐scores on the risk of clinical progression and longitudinal cognitive decline while including temporoparietal GM as a covariate. We then compared the W‐scores between the two hypometabolic subtypes of AD.ResultHigher W‐scores, indicating higher CR, predicted a lower risk of prodromal AD participants for the progression to AD dementia (hazards ratio = 0.32, 95%CI = [0.19;0.52]). W‐scores were also associated with a slower longitudinal cognitive decline for memory (β = 0.11,p<0.01) and language performance (β = 0.12,p = 0.017) in the subsample of CN and prodromal AD (Fig. 2). The typical hypometabolic subtype showed on average higher W‐scores than the limbic‐predominant subtype in prodromal AD and AD dementia groups.ConclusionConsistent with previous research, CR as assessed by W‐scores was predictive of a lower risk of clinical progression and slower longitudinal cognitive decline. The typical subtype demonstrated higher W‐scores, which suggests a stronger resilience to the impact of neuropathological change on cognition. Future analysis will investigate longitudinal changes in W‐scores and factors contributing to the observed differences, as well as potential explanations for subtype differences.