Evidence map›Paper›PMID 39240044›Full record

ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Pathways to personalized medicine-Embracing heterogeneity for progress in clinical therapeutics research in Alzheimer's disease.

Steven E Arnold, Bradley T Hyman, Rebecca A Betensky, Hiroko H Dodge

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Trial
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  10. Pooling Alzheimer's disease: when methodological rigor risks obscuring biological complexity.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  11. Article
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  16. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Steven E ArnoldDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-9487-415X
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Rebecca A BetenskyDepartment of Biostatistics, New York University School of Global Public Health, New York, New York, USA.
Hiroko H DodgeDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Funding

Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Hyun-Sik Yang · 2010 to 2026
$50.2M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Challenger FoundationNIA NIH HHS P01 AG036694NIA NIH HHS P30 AG062421NIH HHS P30 AG062421
6 · The paper itself

Abstract

Biological and clinical heterogeneity is a major challenge in research for developing new treatments for Alzheimer's disease (AD). AD may be defined by its amyloid beta and tau pathologies, but we recognize that mixed pathologies are common, and that diverse genetics, central nervous system (CNS) and systemic pathophysiological processes, and environmental/experiential factors contribute to AD's diverse clinical and neuropathological features. All these factors are rational targets for therapeutic development; indeed, there are hundreds of candidate pharmacological, dietary, neurostimulation, and lifestyle interventions that show benefits in homogeneous laboratory models. Conventional clinical trial designs accommodate heterogeneity poorly, and this may be one reason that progress in translating candidate interventions has been so difficult. We review the challenges of AD's heterogeneity for the clinical trials enterprise. We then discuss how advances in repeatable biomarkers and digital phenotyping enable novel "single-case" and adaptive trial designs to accelerate therapeutics development, moving us closer to personalized research and medicine for AD. HIGHLIGHTS: Alzheimer's disease is diverse in its clinical features, course, risks, and biology. Typical randomized controlled trials are exclusive and necessarily large to attain arm comparability with broad outcomes. Repeated blood biomarkers and digital tracking can improve outcome measure precision and sensitivity. This enables the use of novel "single-case" and adaptive trial designs for inclusivity, rigor, and efficiency.

Indexed as

Alzheimer DiseasePrecision MedicineAdaptive Clinical Trials as TopicBiomarkersClinical Trials as TopicHumansBiomarkersAlzheimer's diseaseamyloidbiomarkersclinical trialscombination therapyco‐morbiditiesdementiadigital healthheterogeneityinflammationpersonalized medicinerisk factorstau

Identifiers

PMID39240044
PMCPMC11485305

What OpenQuestion holds

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Registered trials

None linked

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.