Non-memory cognitive symptom development in Alzheimer's disease.
Alzheimer’s
age
cognition
progression
symptom change
symptom history
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
05
08
2019
accepted:
17
02
2020
pubmed:
23
2
2020
medline:
23
6
2021
entrez:
21
2
2020
Statut:
ppublish
Résumé
Memory is known to be the most common first symptom in Alzheimer's disease (AD). Assessing non-memory cognitive symptom development in AD is important for understanding disease progression and the potential identification of treatment-responsive subtypes. Data from the National Alzheimer's Coordinating Center were examined. Logistic regression models were fitted evaluating the development of judgement, language, visuospatial and attention symptoms at first and second visits to Alzheimer's Disease Centers. Predictors were age and prior symptoms, adjusting for symptom length and sex. The models were then refitted assessing apolipoprotein E ε4 (APOE-ε4) effects. Each decade reduction in presentation age increased the odds of language, visuospatial and attention symptom development at both visits by 8%-18% (P < 0.05, all tests), and judgement symptoms at the second visit by 13% (P < 0.05). Prior symptoms were not equally predictive of symptom development. For example, having first predominant language symptoms carried the lowest risk of developing other first-visit symptoms and having memory symptoms was a stronger predictor of developing judgement than other symptoms. The APOE-ε4 gene showed little impact on symptom development when included as a predictor. Our findings provide support for the concept that younger-onset AD is associated with the progressive development of more non-memory symptoms beyond the first time point. Associations between symptoms were evident, which may reflect that pathology can remain isolated in a network for some time. APOE-ε4 status had little influence on cognitive symptom development which may indicate that the effect it has occurs very early in the disease course.
Sections du résumé
BACKGROUND AND PURPOSE
Memory is known to be the most common first symptom in Alzheimer's disease (AD). Assessing non-memory cognitive symptom development in AD is important for understanding disease progression and the potential identification of treatment-responsive subtypes.
METHODS
Data from the National Alzheimer's Coordinating Center were examined. Logistic regression models were fitted evaluating the development of judgement, language, visuospatial and attention symptoms at first and second visits to Alzheimer's Disease Centers. Predictors were age and prior symptoms, adjusting for symptom length and sex. The models were then refitted assessing apolipoprotein E ε4 (APOE-ε4) effects.
RESULTS
Each decade reduction in presentation age increased the odds of language, visuospatial and attention symptom development at both visits by 8%-18% (P < 0.05, all tests), and judgement symptoms at the second visit by 13% (P < 0.05). Prior symptoms were not equally predictive of symptom development. For example, having first predominant language symptoms carried the lowest risk of developing other first-visit symptoms and having memory symptoms was a stronger predictor of developing judgement than other symptoms. The APOE-ε4 gene showed little impact on symptom development when included as a predictor.
CONCLUSIONS
Our findings provide support for the concept that younger-onset AD is associated with the progressive development of more non-memory symptoms beyond the first time point. Associations between symptoms were evident, which may reflect that pathology can remain isolated in a network for some time. APOE-ε4 status had little influence on cognitive symptom development which may indicate that the effect it has occurs very early in the disease course.
Identifiants
pubmed: 32078209
doi: 10.1111/ene.14185
pmc: PMC10124327
mid: NIHMS1573400
doi:
Substances chimiques
Apolipoprotein E4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
995-1002Subventions
Organisme : NIA NIH HHS
ID : P50 AG005142
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047366
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010129
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG033514
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG053760
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005131
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG035982
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013846
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047270
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG012300
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008017
Pays : United States
Informations de copyright
© 2020 European Academy of Neurology.
Références
Alzheimer Dis Assoc Disord. 2013 Jul-Sep;27(3):218-25
pubmed: 23954887
Brain. 2000 Mar;123 Pt 3:484-98
pubmed: 10686172
Alzheimers Dement. 2015 Nov;11(11):1349-57
pubmed: 25916562
Cortex. 2007 Oct;43(7):835-45
pubmed: 17941342
J Clin Exp Neuropsychol. 2006 Aug;28(6):884-97
pubmed: 16822730
Lancet Neurol. 2011 Mar;10(3):280-8
pubmed: 21185234
Neurology. 1984 Jul;34(7):939-44
pubmed: 6610841
Neurology. 2011 May 17;76(20):1720-5
pubmed: 21576687
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10256-61
pubmed: 20479234
Dement Geriatr Cogn Disord. 2012;33(2-3):189-203
pubmed: 22572810
Neurology. 1996 Jan;46(1):136-41
pubmed: 8559362
Int J Psychiatry Med. 2006;36(4):401-12
pubmed: 17407994
Science. 1993 Aug 13;261(5123):921-3
pubmed: 8346443
Lancet Neurol. 2010 Nov;9(11):1118-27
pubmed: 20934914
J Neurol Neurosurg Psychiatry. 2011 Jan;82(1):45-51
pubmed: 20562467
Neurology. 1994 Jul;44(7):1215-20
pubmed: 8035918
Alzheimer Dis Assoc Disord. 2006 Oct-Dec;20(4):210-6
pubmed: 17132964
J Alzheimers Dis. 2010;19(4):1401-8
pubmed: 20061618
Alzheimers Dement. 2016 Aug;12(8):862-71
pubmed: 26993346
J Alzheimers Dis. 2012;30(1):101-8
pubmed: 22366769