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Early- versus late-onset Alzheimer's disease in clinical practice : Cognitive and global outcomes over 3 years

Wattmo, Carina LU and Wallin, Åsa LU (2017) In Alzheimer's Research and Therapy 9(1).
Abstract

Background: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. Methods: This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years). At baseline and semi-annually, patients were assessed using cognitive, global and activities of daily living (ADL) scales, and the dose of ChEI was recorded. Potential predictors... (More)

Background: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. Methods: This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years). At baseline and semi-annually, patients were assessed using cognitive, global and activities of daily living (ADL) scales, and the dose of ChEI was recorded. Potential predictors of decline were analysed using mixed-effects models. Results: Six-month response to ChEI therapy and long-term prognosis in cognitive and global performance were similar between the age-at-onset groups. However, deterioration was significantly faster when using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) over 3 years in participants with EOAD than in those with LOAD; hence, prediction models for the mean ADAS-Cog trajectories are presented. The younger cohort had a larger proportion of homozygote apolipoprotein E (APOE) ϵ4 allele carriers than the older cohort; however, APOE genotype was not a significant predictor of cognitive impairment in the multivariate models. A slower rate of cognitive progression was related to initiation of ChEIs at an earlier stage of AD, higher ChEI dose and fewer years of education in both groups. In LOAD, male sex, better instrumental ADL ability and no antipsychotic drug use were additional protective characteristics. The older patients received a lower ChEI dose than the younger individuals during most of the study period. Conclusions: Although the participants with EOAD showed a faster decline in ADAS-Cog, had a longer duration of AD before diagnosis, and had a higher frequency of two APOE ϵ4 alleles than those with LOAD, the cognitive and global responses to ChEI treatment and the longitudinal outcomes after 3 years were similar between the age-at-onset groups. A higher mean dose of ChEI and better cognitive status at the start of therapy were independent protective factors in both groups, stressing the importance of early treatment in adequate doses for all patients with AD.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholinesterase inhibitors, Cognition, Early-onset Alzheimer's disease, Late-onset Alzheimer's disease, Longitudinal study, Mixed-effects models, Predictors
in
Alzheimer's Research and Therapy
volume
9
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85028631346
  • wos:000409178600001
ISSN
1758-9193
DOI
10.1186/s13195-017-0294-2
language
English
LU publication?
yes
id
c1f1124d-afd0-4683-a2e1-a6c8d1fe76ae
date added to LUP
2017-10-06 09:45:27
date last changed
2018-01-16 13:21:14
@article{c1f1124d-afd0-4683-a2e1-a6c8d1fe76ae,
  abstract     = {<p>Background: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. Methods: This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset &lt; 65 years) and 874 had LOAD (age at onset ≥ 65 years). At baseline and semi-annually, patients were assessed using cognitive, global and activities of daily living (ADL) scales, and the dose of ChEI was recorded. Potential predictors of decline were analysed using mixed-effects models. Results: Six-month response to ChEI therapy and long-term prognosis in cognitive and global performance were similar between the age-at-onset groups. However, deterioration was significantly faster when using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) over 3 years in participants with EOAD than in those with LOAD; hence, prediction models for the mean ADAS-Cog trajectories are presented. The younger cohort had a larger proportion of homozygote apolipoprotein E (APOE) ϵ4 allele carriers than the older cohort; however, APOE genotype was not a significant predictor of cognitive impairment in the multivariate models. A slower rate of cognitive progression was related to initiation of ChEIs at an earlier stage of AD, higher ChEI dose and fewer years of education in both groups. In LOAD, male sex, better instrumental ADL ability and no antipsychotic drug use were additional protective characteristics. The older patients received a lower ChEI dose than the younger individuals during most of the study period. Conclusions: Although the participants with EOAD showed a faster decline in ADAS-Cog, had a longer duration of AD before diagnosis, and had a higher frequency of two APOE ϵ4 alleles than those with LOAD, the cognitive and global responses to ChEI treatment and the longitudinal outcomes after 3 years were similar between the age-at-onset groups. A higher mean dose of ChEI and better cognitive status at the start of therapy were independent protective factors in both groups, stressing the importance of early treatment in adequate doses for all patients with AD.</p>},
  articleno    = {70},
  author       = {Wattmo, Carina and Wallin, Åsa},
  issn         = {1758-9193},
  keyword      = {Cholinesterase inhibitors,Cognition,Early-onset Alzheimer's disease,Late-onset Alzheimer's disease,Longitudinal study,Mixed-effects models,Predictors},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research and Therapy},
  title        = {Early- versus late-onset Alzheimer's disease in clinical practice : Cognitive and global outcomes over 3 years},
  url          = {http://dx.doi.org/10.1186/s13195-017-0294-2},
  volume       = {9},
  year         = {2017},
}