Abstract
BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder with extensive neuropathological and clinical heterogeneity.ObjectiveWe assessed empirically derived brain atrophy profiles in relation to incident AD dementia.MethodsA secondary data analysis of two prospective cohort studies was conducted, including participants without dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 1703) and the Czech Brain Aging Study (CBAS; n = 385). Latent profile analysis identified profiles across 10 pre-selected, AD-related brain regions derived from structural magnetic resonance imaging (hippocampus, middle temporal, superior temporal, precuneus, anterior cingulate, medial orbitofrontal, pericalcarine, precentral, lingual, caudate regions). Cox proportional hazards regression assessed how profiles related to incident AD dementia.ResultsFour profiles emerged in ADNI: Minimal (n = 192), Mild (n = 691), Moderate (n = 567), and Severe (n = 253) Atrophy. Two profiles emerged in CBAS: Mild (n = 208) and Severe (n = 177) Atrophy. In ADNI, participants with Mild (HR = 3.11, 95% CI [1.43, 6.78]), Moderate (HR = 7.58, 95% CI [3.45, 16.68]), and Severe (HR = 16.95, 95% CI [7.39, 39.86]) Atrophy (versus Minimal) had increased incident AD dementia risk. In CBAS, participants with Severe Atrophy (versus Mild) had increased incident AD dementia risk (HR = 3.51, 95% CI [2.14, 5.77]). Controlling for baseline cognition attenuated effects for Mild (ADNI) and Severe (CBAS) Atrophy to non-significance.ConclusionsIn two geographically and culturally distinct samples, magnitude of atrophy, not pattern across regions, determined classification into profiles, which predicted incident AD dementia. Findings highlight generalized, rather than region-specific, atrophy patterns associated with AD, and underscore the clinical utility of brain volumetry in identifying those with elevated incident AD dementia risk.