Background: The ɛ4-allele of apolipoprotein E
(APOE-ɛ4) increases the risk not only for
Alzheimer’s disease (AD), but also for Parkinson’s disease dementia and
dementia with Lewy bodies (collectively, Lewy body dementia [LBD]).
Hippocampal volume is an important neuroimaging biomarker for AD and LBD,
although its association with APOE-ɛ4 is
inconsistently reported. We investigated the association of
APOE-ε4 with hippocampal atrophy quantified
using magnetic resonance imaging in AD and LBD.
Methods: Electronic databases (PubMed, Embase,
PsycINFO, Scopus, Web of Science) were systematically searched for studies
published up until December 31st, 2020.
Results: Thirty-nine studies (25 cross-sectional,
14 longitudinal) were included. We observed that: (1)
APOE-ε4 was associated with greater rate of
hippocampal atrophy in AD and those who progressed from mild cognitive
impairment to AD, (2) APOE-ε4 carriers showed
greater involvement of cornu ammonis-1 hippocampal subfield versus
non-carriers in AD, (3) APOE-ɛ4 may influence
hippocampal atrophy in dementia with Lewy bodies, although longitudinal
investigations are required, and (4) APOE-ε4
associated with earlier rather than very late expression of mediotemporal
degeneration and memory-related neurocognitive impairment.
Conclusions: The role of
APOE-ɛ4 in modulating hippocampal phenotypes
may be further clarified through more homogenous, well-powered,
pathology-proven studies. Understanding the underlying mechanisms will
facilitate development of prevention strategies targeting
APOE-ɛ4.