SynthesisNeurology2020
Biological subtypes of Alzheimer disease: A systematic review and meta-analysis.
Synthesis in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 3 of them syntheses that pooled it.
What it found
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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
254 citing papers in PubMed, 3 syntheses or guidelines pooled it, 390 citations in OpenAlex.
- Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis.Neuropsychology review · 2023Pooled it
- The hippocampal sparing subtype of Alzheimer's disease assessed in neuropathology and in vivo tau positron emission tomography: a systematic review.Acta neuropathologica communications · 2022Pooled it
- White matter variability, cognition, and disorders: a systematic review.Brain structure & function · 2022Pooled it
- Brain patterns and risk factors in the FINGER RCT multimodal lifestyle intervention.The journal of prevention of Alzheimer's disease · 2025Trial
- Differential response to donepezil in MRI subtypes of mild cognitive impairment.Alzheimer's research & therapy · 2023Trial
- Discovering Heterogeneous Neurodegenerative Disease Patterns From MRI Data for Improved Prediction.Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention · 2027Article
- Learning robust and task-invariant functional representation from fMRI through Siamese self-supervised learning.Medical image analysis · 2026Article
- Global and regional amyloid-β in explaining APOE-ε4 and sex associations with medial temporal tau: a neuropathology study.Acta neuropathologica · 2026Article
- Multimodal neuroimaging in dementia and neurodegenerative disorders: complementary roles of clinically available nuclear medicine and MRI in the era of disease-modifying therapies.Japanese journal of radiology · 2026Review
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
- Beyond statistical thresholds: Mapping sequential ATN cascade transitions via brain structural topography in Alzheimer's disease.Science advances · 2026Article
- Atypical Alzheimer disease: a multi-axis framework toward defining heterogeneity.Nature reviews. Neurology · 2026Review
- Machine learning-derived Alzheimer's disease dimensions: neuroanatomical, cognitive, clinical, functional, and genetic risk heterogeneity signatures.medRxiv : the preprint server for health sciences · 2026Article
- Cognitive heterogeneity in mild cognitive impairment due to Alzheimer's disease pathology.Neural regeneration research · 2026Article
- What Do Persistent Misclassifications Tell Us About Alzheimer's Disease Detection using Structural MRI?medRxiv : the preprint server for health sciences · 2026Article
- Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk.medRxiv : the preprint server for health sciences · 2026Article
- Subtyping and staging of Alzheimer's disease from routine structural MRI with PHASE-AD.medRxiv : the preprint server for health sciences · 2026Article
- Alzheimer's disease and cerebrovascular biomarkers in relation to odor identification in a naturalistic clinical cohort.Alzheimer's research & therapy · 2026Article
- Marine Lipids and Alzheimer's Disease: Biochemistry, Bioaccessibility/Bioavailability, Metabolism, and Health Effects.Marine drugs · 2026Review
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
194 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data.
methodsEMBASE, PubMed, and Web of Science databases were consulted until July 2019.
resultsNeuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels.
conclusionWe identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
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Identifiers
What OpenQuestion 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 OpenQuestion graph.