Abstract
BackgroundWhether 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.MethodsThis 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.ResultsSix-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.ConclusionsAlthough 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.
Highlights
Whether age at onset influences Alzheimer’s disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear
Socio-demographic and clinical characteristics according to age at onset of AD The 1017 Swedish Alzheimer Treatment Study (SATS) participants were divided into two cohorts according to their age at onset of AD: early-onset Alzheimer’s disease (EOAD) (< 65 years, n = 143 [14%]) and late-onset Alzheimer’s disease (LOAD) (≥ 65 years, n = 874 [86%])
In this study performed in routine clinical practice, the 6-month cognitive and global responses to ChEI therapy and the longitudinal outcomes after 3 years were similar between the age-at-onset groups; a somewhat faster decline in the EOAD group at some time points was detected when we used the ADAS-Cog scale
Summary
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. People who have a clinical onset of Alzheimer’s disease (AD) before the age of 65 years are diagnosed with early-onset Alzheimer’s disease (EOAD). EOAD might be a separate, more severe entity than late-onset Alzheimer’s disease (LOAD). Patients with AD who died before 80 years of age had a more widespread and severe cholinergic deficit with. Younger persons are often more educated than older individuals and have a higher cognitive reserve capacity that could lead to a delayed diagnosis [8].
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