Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts

INTRODUCTION: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach. METHODS: We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters. RESULTS: In each cohort, a two-clusters solution best fitted the data (cophenetic correlation >0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P < .05). CONCLUSIONS: We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

The hippocampus constructs narrative memories across distant events

Supplemental files for biorxi

Time regained: how the human brain constructs memory for time

Life's episodes unfold against a context that changes with time. Recent neuroimaging studies have revealed significant findings about how specific areas of the human brain may support the representation of temporal information in memory. A consistent theme in these studies is that the hippocampus appears to play a central role in representing temporal context, as operationalized in neuroimaging studies of arbitrary lists of items, sequences of items, or meaningful, lifelike events. Additionally, activity in a posterior medial cortical network may reflect the representation of generalized temporal information for meaningful events. The hippocampus, posterior medial network, and other regions-particularly in prefrontal cortex-appear to play complementary roles in memory for temporal context

Narratives bridge the divide between distant events in episodic memory

These data supplement the manuscript of the same title

The hippocampus constructs narrative memories across distant events

Life's events are scattered throughout time, yet we often recall different events in the context of an integrated narrative. Prior research suggests that the hippocampus, which supports memory for past events, can support the integration of overlapping associations or separate events in memory. However, the conditions that lead to hippocampus-dependent memory integration are unclear. We used functional brain imaging to test whether the opportunity to form a larger narrative (narrative coherence) drives hippocampal memory integration. During encoding of fictional stories, patterns of hippocampal activity, including activity at boundaries between events, were more similar between distant events that formed one coherent narrative, compared with overlapping events taken from unrelated narratives. One day later, the hippocampus preferentially supported detailed recall of coherent narrative events, through reinstatement of hippocampal activity patterns from encoding. These findings demonstrate a key function of the hippocampus: the integration of events into a narrative structure for memory