Longitudinal trajectory of Amyloid-related hippocampal subfield atrophy in nondemented elderly.

Hippocampal atrophy and abnormal ß-Amyloid (Aß) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aß-associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aß correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET-Aß in AD-vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto-segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aß-related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aß correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal-to-widespread trajectory of Aß-associated hippocampal subfield atrophy over disease progression in nondemented elderly.

Cerebral Small Vessel Disease Influences Hippocampal Subfield Atrophy in Mild Cognitive Impairment.

To investigate patterns of hippocampal subfield atrophy among patients with amnestic mild cognitive impairment, stratified by severity of small vessel disease (SVD) and corresponding associations with cognitive domains. One hundred seventy-six MCI subjects (mean age = 65.56 years, SD = 8.77) underwent neuropsychological assessments and magnetic resonance imaging. SVD was rated 0 (no SVD), 1 (mild SVD) and 2 (moderate to severe SVD) based on load of white matter hyperintensities (WMH) and lacunes. Demographics, cerebrovascular risk factors, grey and white matter volumes and hippocampal subfield atrophies were compared across SVD severity through ANCOVA analyses. Subjects were categorized into positive or negative SVD-hippocampal subfield atrophy (HSA) and influence of positive SVD-HSA on episodic memory and frontal executive function was evaluated through ANCOVA analyses. All analyses corrected for covariates and bias-corrected bootstrap estimation with 1000 resamples was applied with Bonferroni correction. Hippocampal subfield atrophy worsened with increasing SVD severity. Positive SVD-HSA was characterised by significant atrophy in the subiculum, CA1, CA4, molecular layer and dentate gyrus. Greater atrophy was seen with moderate to severe SVD compared to mild SVD in these subfields. Atrophy in the five subfields of SVD-HSA was significantly associated with poor episodic memory and frontal executive function. Presence and burden of SVD influences the pattern and severity of hippocampal subfield atrophy. SVD-related hippocampal subfield atrophy is associated with poorer episodic memory and frontal executive function in mild cognitive impairment.