ReviewNeuroImage. Clinical2026
Impact of apolipoprotein Ε4 (APOE ε4) on neuroimaging outcomes in cognitively healthy midlife adults: A systematic review.
Review in NeuroImage. Clinical, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe apolipoprotein E ε4 (APOE ε4) allele is the strongest genetic risk factor for Alzheimer's disease (AD); however, its neurobiological impact assessed by neuroimaging outcomes during midlife, before the onset of cognitive impairment, has not been summarised. This systematic review synthesises evidence on neuroimaging differences associated with APOE ε4-carrier status in cognitively healthy midlife adults and evaluates whether AD-related risk can be detected across imaging modalities.
methodsA literature search was conducted up until November 2025 to identify studies reporting neuroimaging outcomes in healthy adults aged 30-60 years with known APOE genotype. Eligible studies employed positron emission tomography (PET) and/or magnetic resonance imaging (MRI) and reported outcomes stratified by APOE ε4-carrier status. Risk of bias was assessed using the ROBINS-E tool, and a narrative synthesis was performed.
resultsSearches yielded 7786 articles, and 46 studies met the inclusion criteria. Nine studies used PET, forty used MRI, and three of these studies employed both modalities. Substantial heterogeneity in methods and outcome reporting meant that a meta-analysis was not feasible. PET evidence consistently identified greater amyloid deposition and lower glucose metabolism in midlife APOE ε4-carriers compared with non-carriers, while MRI findings most reliably indicate higher cerebral blood flow. In contrast, other MRI-derived structural, microstructural, functional, and metabolic findings were mixed and largely inconclusive.
conclusionCognitively healthy APOE ε4-carriers demonstrate measurable neurobiological differences as early as midlife, consistent with a preclinical vulnerability associated with genetic risk for AD. These findings highlight the importance of characterising APOE-related mechanisms during midlife to inform early detection strategies and the development of preventative interventions for AD.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.