Cortical thinning in early vs. Late-onset alzheimer’s disease: brain-behavior relationships and genetic Influences

Abstract

Our own clinical observations concur with those of this symposium in that early-onset AD appears to be more likely to be associated with non-amnesic forms of cognitive impairment, particularly executive, visuospatial, and language dysfunction. This “atypical” pattern is also associated with non-carrier status of the APOE e4 allele. We sought to compare patterns of cortical thinning in early vs late onset AD and in those with and without APOE-e4 to further understand these factors. We performed cortical thickness analysis as previously described (Dickerson et al., Cerebral Cortex, 2009) using both a hypothesis-driven and an exploratory approach, with an emphasis on the “cortical signature of AD” set of regions consistently affected in mild AD dementia. Younger age of onset was associated with more prominent atrophy in dorsal frontoparietal regions along with executive dysfunction. Older age of onset was associated with more prominent medial temporal lobe atrophy along with a temporolimbic form of memory impairment. Similar findings were present in relation to APOE carrier status, with non-carriers demonstrating more frontoparietal atrophy and carriers demonstrating more MTL atrophy. Although late onset AD may present atypically with non-memory dysfunction, the clinical and neuranatomic phenotype of early onset AD appears to consistently differ substantially from that of typical late onset AD. Further investigation of factors influencing the various forms of presentation of AD may be important for refining diagnostic and monitoring criteria, including for clinical trials.