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IC‐P‐103: RELATIONSHIPS BETWEEN P‐TAU AND CHANGES IN MYELIN CONTENT AND COGNITIVE PERFORMANCE
Author(s) -
Lee Yang Kao,
Kohli Akshay,
Dean Doug C.,
Jonaitis Erin,
Koscik Rebecca L.,
Alexander Andrew L.,
Zetterberg Henrik,
Blennow Kaj,
Johnson Sterling C.,
Asthana Sanjay,
Bendlin Barbara B.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4217
Subject(s) - psychology , white matter , myelin , longitudinal study , neuropsychology , medicine , cognition , cognitive decline , cohort , neuroscience , gastroenterology , oncology , pathology , central nervous system , dementia , disease , magnetic resonance imaging , radiology
Background: Abnormal b-Amyloid (Ab) deposition and hippocampal atrophy are characteristic of Alzheimer’s disease (AD) (Jack et al., 1997, 2013; Barnes et al., 2009). Based on the Dynamic Biomarkers of the AD Pathological Cascade model, Ab deposition is hypothesized to precede hippocampal atrophy and reaches a plateau at the dementia stage or earlier (Jack et al., 2010; Jack et al., 2013). In line with this model, studies have shown an association between Ab and hippocampal atrophy early in the dementia continuum, but not AD (Chetelat et al., 2010). Nonetheless, given the anatomical heterogeneity of the hippocampus, how Ab relates to specific hippocampal subfield atrophy and its longitudinal progression in pre-dementia stage remains unclear. We hypothesized that elevated Ab burden was associated with selective hippocampal subfield atrophy at baseline, and progressed to involve other subfields over time in elderly subjects with no cognitive impairment (NCI) or mild cognitive impairment (MCI).Methods: We examined hippocampal subfield atrophy in association with Ab both crosssectionally and longitudinally in two independent datasets: the ADNI dataset (52 NCI and 77 MCI) and a Singaporean dataset (15 NCI and 76 MCI). Participants underwent one amyloid PET and at least two structural MRI scans over a maximum of four years (ADNI dataset) or two years (Singaporean dataset). Hippocampal subfields were segmented using a novel auto-segmentation in FreeSurfer based on an ex vivo ultra-high-resolution atlas with post-mortem hippocampal tissue (Iglesias et al., 2015, 2016). Furthermore, we investigated whether any observed Ab-related progressive subfield atrophy correlated with memory decline. Results: Replicated in both datasets, greater Ab burden correlated to CA1 atrophy at baseline and greater CA1 volume decline in NCI (Figure 1). InMCI, both datasets showed morewidespread progressive atrophy over time, consistently in the CA1, molecular layer, and subiculum (Figure 2). Moreover, memory decline correlated with those Ab-related progressive subfield atrophy in Singaporean MCI patients. Conclusions: There was converging evidence showing a longitudinal trajectory of focal-to-widespread subfield atrophy in association with Ab in non-demented elderly. These may serve as potential imaging markers for the early detection and prevention of memory impairment and/or dementia.