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

Humans Female Aged Male Alzheimer Disease / diagnosis Neurodegenerative Diseases Cross-Sectional Studies Cognitive Dysfunction / epidemiology tau Proteins Neuropsychological Tests Disease Progression Biomarkers Amyloid beta-Peptides

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
14 02 2023
Historique:
received: 31 05 2022
accepted: 20 09 2022
pubmed: 3 11 2022
medline: 16 2 2023
entrez: 2 11 2022
Statut: ppublish

Résumé

Plasma 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. Cognitively 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. The 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%, 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.

Sections du résumé

BACKGROUND AND OBJECTIVES
Plasma 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.
METHODS
Cognitively 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.
RESULTS
The 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.

Identifiants

DOI: 10.1212/WNL.0000000000201517 PMID: 36323521 PMC: PMC9969916
pubmed: 36323521
pii: WNL.0000000000201517
doi: 10.1212/WNL.0000000000201517
pmc: PMC9969916
doi:

Substances chimiques

tau Proteins 0
Biomarkers 0
Amyloid beta-Peptides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e683-e693

Subventions

Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States

Informations de copyright

© 2022 American Academy of Neurology.

Références

Neurology. 2019 Oct 22;93(17):e1647-e1659
pubmed: 31371569
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
J Clin Psychiatry. 2022 Mar 16;83(3):
pubmed: 36036661
Acta Neuropathol. 2018 Dec;136(6):821-853
pubmed: 30488277
Acta Neuropathol. 2020 Sep;140(3):267-278
pubmed: 32720099
J Alzheimers Dis. 2021;81(3):1295-1309
pubmed: 33935098
J Alzheimers Dis. 2018;62(1):227-238
pubmed: 29439333
J Alzheimers Dis. 2020;75(1):277-288
pubmed: 32250302
JAMA Neurol. 2019 May 1;76(5):598-606
pubmed: 30830207
Nat Rev Drug Discov. 2022 Apr;21(4):306-318
pubmed: 35177833
Brain. 2021 Feb 12;144(1):325-339
pubmed: 33257949
Int Psychogeriatr. 2018 Feb;30(2):171-175
pubmed: 29448970
Neurobiol Dis. 2014 Dec;72 Pt A:3-12
pubmed: 25173806
Mol Brain. 2019 Mar 28;12(1):26
pubmed: 30922367
Dement Geriatr Cogn Disord. 2008;25(6):559-63
pubmed: 18536520
EMBO Mol Med. 2016 Jun 01;8(6):595-608
pubmed: 27025652
JAMA Neurol. 2019 Jul 1;76(7):791-799
pubmed: 31009028
Front Aging Neurosci. 2021 May 24;13:643271
pubmed: 34108874
Alzheimers Dement. 2016 Feb;12(2):195-202
pubmed: 26096665
J Alzheimers Dis. 2020;76(3):1017-1027
pubmed: 32597801
Alzheimers Dement. 2015 Mar;11(3):249-57.e1
pubmed: 25217292
Int Psychogeriatr. 2018 Feb;30(2):233-244
pubmed: 28879833
Am J Geriatr Psychiatry. 2016 Nov;24(11):1095-1104
pubmed: 27426238
J Alzheimers Dis. 2019;71(2):477-501
pubmed: 31424398
Neurology. 2022 May 24;98(21):e2132-e2139
pubmed: 35351783
Arch Clin Neuropsychol. 2006 Jan;21(1):15-21
pubmed: 16125364
Int Psychogeriatr. 2022 Feb 08;:1-10
pubmed: 35130991
J Alzheimers Dis. 2021;80(1):459-469
pubmed: 33554909
Alzheimers Dement (N Y). 2020 Sep 06;6(1):e12016
pubmed: 32995467
Alzheimers Dement. 2021 Jul;17(7):1145-1156
pubmed: 33491853
J Alzheimers Dis. 2017;56(3):929-938
pubmed: 28059789
Neurology. 1994 Dec;44(12):2308-14
pubmed: 7991117
Int J Geriatr Psychiatry. 2021 Sep;36(9):1398-1406
pubmed: 33778998
Arch Neurol. 2011 Mar;68(3):351-6
pubmed: 21403020
Alzheimers Dement. 2018 Aug;14(8):989-997
pubmed: 29626426
Nat Med. 2020 Mar;26(3):379-386
pubmed: 32123385
Nat Rev Neurol. 2018 Oct;14(10):577-589
pubmed: 30171200
J Geriatr Psychiatry Neurol. 2023 Mar;36(2):107-120
pubmed: 35430902
Transl Psychiatry. 2021 Jan 26;11(1):76
pubmed: 33500386
Lancet Neurol. 2010 Jan;9(1):119-28
pubmed: 20083042
Alzheimers Dement. 2020 Jan;16(1):192-199
pubmed: 31914223
Alzheimers Res Ther. 2022 Jan 5;14(1):2
pubmed: 34986891
Lancet Neurol. 2020 May;19(5):422-433
pubmed: 32333900
Alzheimers Dement. 2017 Aug;13(8):841-849
pubmed: 28734653
Mol Psychiatry. 2021 Feb;26(2):429-442
pubmed: 33106600
J Geriatr Psychiatry Neurol. 2022 May;35(3):434-441
pubmed: 34036829
J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):233-9
pubmed: 11001602
Neurology. 2016 Aug 2;87(5):539-47
pubmed: 27371494

Auteurs

Maryam Ghahremani (M)

From 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 Wang (M)

From 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 Chen (HY)

From 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 Zetterberg (H)

From 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 Smith (E)

From 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 Ismail (Z)

From 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

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Disciplines et activités comportementales › Tests psychologiques › Tests neuropsychologiques › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Plasma Phosphorylated Tau at Threonine 181 and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Plasma Phosphorylated Tau at Threonine 181 and...