Evidence map›Paper›PMID 36323521›Full record

ArticleNeurology2023

Plasma Phosphorylated Tau at Threonine 181 and Neuropsychiatric Symptoms in Preclinical and Prodromal Alzheimer Disease.

Maryam Ghahremani, Meng Wang, Hung-Yu Chen, Henrik Zetterberg, Eric Smith, Zahinoor Ismail, Alzheimer's Disease Neuroimaging Initiative*

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
–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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Mild Behavioral Impairment: A Population-Based Study.The Journal of neuropsychiatry and clinical neurosciences · 2026
    Article
  11. Article
  12. Observational
  13. Article
  14. Article
  15. Article
  16. Review
  17. Updates and future perspectives on neuropsychiatric symptoms in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  18. Article
  19. Review
  20. Observational
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

7 authors.

Maryam GhahremaniFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom.
Meng WangFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom.
Hung-Yu ChenFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom.
Henrik ZetterbergFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom.ORCID 0000-0002-4671-6763
Eric SmithFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom.ORCID 0000-0003-3956-1668
Zahinoor IsmailFrom the Department of Psychiatry (M.G., H.-Y.C., Z.I.), Hotchkiss Brain Institute (M.G., M.W., H.-Y.C., E.S., Z.I.), Department of Clinical Neurosciences (M.W., E.S., Z.I.), Cumming School of Medicine, and Department of Community Health Sciences (M.W., E.S., Z.I.), University of Calgary, Alberta, Canada; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.); Hong Kong Center for Neurodegenerative Diseases (H.Z.), China; Mathison Centre for Mental Health Research & Education (Z.I.), University of Calgary, Alberta, Canada; and College of Medicine and Health (Z.I.), University of Exeter, United Kingdom. ismailz@ucalgary.ca.ORCID 0000-0002-5529-3731
Alzheimer's Disease Neuroimaging Initiative*

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

BACKGROUND AND

objectivesPlasma phosphorylated tau at threonine 181 (p-tau181), a well-validated marker of Alzheimer disease (AD) pathologic change, could be a more efficient way to diagnose AD than invasive or expensive biomarkers requiring CSF or PET. In some individuals, neuropsychiatric symptoms (NPS) are the earliest manifestation of AD, observed in advance of clear cognitive decline. However, the few studies assessing AD biomarkers in association with NPS have often had imprecision in capturing behavioral symptoms that represent sequelae of neurodegenerative disease. Thus, the mild behavioral impairment (MBI) construct was developed, framing NPS in a way to improve the precision of risk estimates for disease. MBI core criteria stipulate that NPS emerge de novo in later life and persist for at least 6 months. Here, cross-sectionally and longitudinally, we investigated associations of MBI with p-tau181, neuropsychological test performance, and incident AD.

methodsCognitively unimpaired and mild cognitive impairment (MCI) Alzheimer's Disease Neuroimaging Initiative participants were selected. MBI status was derived from the Neuropsychiatric Inventory (NPI) using a published algorithm. NPI total scores at baseline and year 1 visits were used to operationalize MBI (score >0 at both visits), NPS not meeting the MBI criteria (NPS-not-MBI, score >0 at only 1 visit), and no NPS (score = 0 at both visits). Linear regressions were fitted for cross-sectional analyses; multilevel linear mixed-effects and Cox proportional hazards models were implemented to examine the longitudinal associations of MBI with changes in p-tau181 and cognition and incident dementia.

resultsThe sample included 571 participants (age 72.2 years, 46.8% female, 64.8% MCI). Cross-sectionally (β = 8.1%, 95% CI 1.4%-15.2%, DISCUSSION: These findings extend the evidence base that MBI is associated with elevated risk of cognitive decline and dementia and a sequela of emerging Alzheimer-related proteinopathies. MBI offers a substantial improvement over current approaches that explore behavior as a proxy marker for Alzheimer-related proteinopathies, with both clinical and AD trial enrichment implications.

Indexed as

Alzheimer DiseaseCognitive DysfunctionNeurodegenerative DiseasesAgedAmyloid beta-PeptidesBiomarkersCross-Sectional StudiesDisease ProgressionFemaleHumansMaleNeuropsychological Teststau ProteinsAmyloid beta-PeptidesBiomarkerstau Proteins

Identifiers

PMID36323521
PMCPMC9969916

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.