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.

Cortical cerebral microinfarcts predict cognitive decline in memory clinic patients.

Cortical cerebral microinfarcts (CMIs) - a novel MRI marker of cerebral vascular pathology have been linked with dementia and impaired cognition in cross-sectional studies. However, it is unknown if cortical CMIs are an indicator of further cognitive decline. We sought to examine whether baseline cortical CMIs predict cognitive decline in a prospective memory-clinic setting. A total of 313 patients with baseline 3T MRI scans and at least two neuropsychological assessments obtained a minimum of one year apart were recruited. Cortical CMIs were graded on baseline MRI according to a validated protocol. The Montreal Cognitive Assessment (MoCA) and a detailed neuropsychological battery were used to assess cognition. Patients with increased cortical CMIs showed greater decline in MoCA and global cognition per year. Patients with > 2 cortical CMIs decline on average by 2 scores on MoCA and 0.5 on global cognition at year two which corresponds to 109.8% and 184.5% greater decline when compared to those without CMIs. Furthermore, cortical CMIs at baseline were associated with accelerated decline in memory and language domains. Similar associations were observed when analysis was restricted to demented patients. Cortical CMIs together with other cerebrovascular disease markers can be used to design clinical trials in vascular cognitive impairment.