The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease.
Alzheimer's disease
behavioral symptoms
locus coeruleus
phenotype
sleep
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
30
11
2021
received:
04
10
2021
accepted:
02
12
2021
pubmed:
5
12
2021
medline:
5
4
2022
entrez:
4
12
2021
Statut:
ppublish
Résumé
The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored. In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed. At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p < 0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD. Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.
Sections du résumé
BACKGROUND AND PURPOSE
The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored.
METHODS
In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed.
RESULTS
At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p < 0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD.
CONCLUSIONS
Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.
Identifiants
pubmed: 34862834
doi: 10.1111/ene.15203
pmc: PMC8901553
mid: NIHMS1771414
doi:
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
957-967Subventions
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIA NIH HHS
ID : K24 AG045333
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG057195
Pays : United States
Organisme : NIA NIH HHS
ID : K24 AG053435
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027859
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060477
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG032289
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG031861
Pays : United States
Organisme : NIA NIH HHS
ID : K08 AG052648
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064314
Pays : United States
Informations de copyright
© 2021 European Academy of Neurology.
Références
Alzheimers Res Ther. 2020 Jan 4;12(1):5
pubmed: 31901236
Lancet Neurol. 2011 Sep;10(9):785-96
pubmed: 21802369
J Alzheimers Dis. 2009;17(1):105-14
pubmed: 19494435
Neurobiol Aging. 2018 Jan;61:1-12
pubmed: 29031088
J Alzheimers Dis. 2017;59(3):975-985
pubmed: 28697559
Alzheimers Dement. 2012 Jan;8(1):1-13
pubmed: 22265587
J Neuropathol Exp Neurol. 2016 Jul;75(7):628-35
pubmed: 27283329
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Eur J Neurol. 2014 Sep;21(9):1149-54, e64-5
pubmed: 24780092
Cureus. 2016 May 27;8(5):e625
pubmed: 27433404
Int J Geriatr Psychiatry. 2017 Dec;32(12):1264-1271
pubmed: 27714849
J Alzheimers Dis. 2018;66(1):139-148
pubmed: 30248052
Alzheimers Dement. 2011 May;7(3):270-9
pubmed: 21514249
Am J Alzheimers Dis Other Demen. 2019 Nov-Dec;34(7-8):433-438
pubmed: 30935215
Psychogeriatrics. 2015 Dec;15(4):242-7
pubmed: 25737233
Brain Commun. 2020;2(1):fcaa068
pubmed: 32671341
Acta Neuropathol. 1966 Mar 4;6(2):181-7
pubmed: 5963288
J Alzheimers Dis Rep. 2021 Mar 08;5(1):171-177
pubmed: 33981954
Neuropathol Appl Neurobiol. 2009 Aug;35(4):406-16
pubmed: 19508444
Mol Psychiatry. 2021 Mar;26(3):897-906
pubmed: 31138892
Alzheimers Dement. 2019 Oct;15(10):1253-1263
pubmed: 31416793
Alzheimers Dement (N Y). 2017 Aug 05;3(3):440-449
pubmed: 29067350
Alzheimers Res Ther. 2017 Aug 31;9(1):70
pubmed: 28859660
Eur Neuropsychopharmacol. 2015 Jul;25(7):1010-7
pubmed: 25891378
Cochrane Database Syst Rev. 2020 Nov 15;11:CD009178
pubmed: 33189083
Brain. 2021 Aug 17;144(7):2186-2198
pubmed: 33693619
Dement Geriatr Cogn Disord. 2012;34(5-6):319-27
pubmed: 23208452
J Alzheimers Dis. 2017;57(1):147-155
pubmed: 28222514
J Geriatr Psychiatry Neurol. 2007 Mar;20(1):29-33
pubmed: 17341768
Alzheimers Dement. 2011 Sep;7(5):532-9
pubmed: 21889116
J Neurol. 2019 Jun;266(6):1490-1500
pubmed: 30968171
Psychiatry Clin Neurosci. 2005 Dec;59(6):730-5
pubmed: 16401251
J Neuropsychiatry Clin Neurosci. 2014 Winter;26(1):73-80
pubmed: 24515678
Alzheimers Dement. 2021 Aug;17(8):1403-1406
pubmed: 33710762
J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9
pubmed: 22002422
Int Psychogeriatr. 2015 Mar;27(3):357-66
pubmed: 25382659
J Geriatr Psychiatry Neurol. 2021 Sep 9;:8919887211044755
pubmed: 34496652
Sci Transl Med. 2020 Jan 1;12(524):
pubmed: 31894103
Front Aging Neurosci. 2020 Mar 06;12:56
pubmed: 32210790
J Alzheimers Dis. 2018;66(1):115-126
pubmed: 30223398
J Alzheimers Dis. 2015;44(2):661-73
pubmed: 25322926
Brain. 2021 Apr 12;144(3):999-1012
pubmed: 33501939
Am J Alzheimers Dis Other Demen. 2018 Mar;33(2):93-99
pubmed: 29210282
J Alzheimers Dis. 2015;46(1):17-34
pubmed: 25720408
Dement Neuropsychol. 2015 Jan-Mar;9(1):2-8
pubmed: 29213935
Neurology. 2011 Nov 8;77(19):1737-44
pubmed: 22031532
Neurology. 1993 Nov;43(11):2412-4
pubmed: 8232972
Brain. 2015 Sep;138(Pt 9):2732-49
pubmed: 26141491
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):233-9
pubmed: 11001602
Neuropathol Appl Neurobiol. 2017 Aug;43(5):393-408
pubmed: 28117917
Acta Neuropathol. 2019 Oct;138(4):597-612
pubmed: 31250152