Early- versus late-onset Alzheimer’s disease – differences in functional impairment

Abstract

Background: Persons with clinical onset of Alzheimer’s disease (AD) before 65 years of age are diagnosed with early-onset AD (EOAD). The prevalence of EOAD is low, but varies among studies from 6% to 16%. Most individuals with EOAD are still working, have an active social life, and might have children living at home. Therefore, the consequences of being diagnosed early with a disease that implies progressive deterioration of cognitive performance and activities of daily living (ADL), and personality and behavior changes, are enormous. These individuals may also have a decreased average life expectancy of 15–18 years. Some studies suggest that EOAD might be a separate, more severe entity than late-onset AD (LOAD). Neuropathological studies have found that younger patients exhibit a higher burden of AD pathology and a larger, more widespread cholinergic deficit than older patients. A faster cognitive progression among patients with EOAD has also been described. The clinical diagnosis of AD in younger persons can be difficult because of atypical symptoms and/or nonamnestic presentations. The present study aimed to investigate the functional outcomes in EOAD versus LOAD, and potential predictors of nursing home placement (NHP). Methods: The Swedish Alzheimer Treatment Study (SATS) is a 3-year, prospective, observational, multicenter study that investigated the long-term effectiveness of cholinesterase inhibitor (ChEI) treatment from various perspectives, e.g., cognition, ADL, and community-based service usage. Among the 1,258 outpatients clinically diagnosed with probable or possible AD, 1,021 had mild-to-moderate AD (Mini-Mental State Examination [MMSE] score, 10–26) at the start of ChEI therapy (baseline). Of these, 143 patients were defined as having EOAD (onset =65 years), and age at onset was missing for 4; thus, 1,017 patients were enrolled in the present study. Participants were assessed for cognitive ability (MMSE) and functional capacity (Instrumental Activities of Daily Living [IADL] scale and Physical Self-Maintenance Scale [PSMS]). The NHP date was recorded if this occurred during the study. Binary logistic regression was used to determine the patient characteristics that affected NHP. Potential predictors were investigated, including: sex, apolipoprotein E e4 carrier status, solitary living, years of education, duration of AD, age at baseline, specific concomitant medications, and cognitive and functional abilities at baseline and their rates of decline. Results: A significant difference in mean (95% confidence interval) IADL score at the start of ChEI treatment was observed between participants in the EOAD and LOAD groups, 13.9 (13.0–14.8) vs. 16.3 (15.9–16.7) points, p<0.001. The corresponding PSMS scores were 6.7 (6.5–6.9) vs. 7.6 (7.5–7.8) points, p<0.001. The IADL capacity was already markedly impaired at baseline; about 40–65% of the participants with EOAD and 55–75% of those with LOAD were dependent on assistance to perform these activities (IADL score, 2–5). The percentage of participants with impairment in the individual IADL items was significantly lower at baseline in the EOAD cohort, except for the “ability to handle finances” task. After 3 years, the IADL capacity had deteriorated further; 70–90% of the remaining participants in both groups could not perform these tasks independently. Thus, younger individuals showed a faster decline in some tasks including “ability to use telephone,” “shopping,” “food preparation,” and “housekeeping.” However, the participants with LOAD still showed worse capacity in “laundry,” “mode of transportation,” and “responsibility for own medications.”Except for physical ambulation (more than 50% of the individuals with LOAD needed assistance; PSMS score, 2–5), most participants could manage their basic ADL independently at baseline. A significantly larger percentage of the participants with LOAD were impaired in the ADL items: “toilet,” “physical ambulation,” and “bathing.” After 3 years, 35–55% of the remaining participants needed assistance in “dressing,” “grooming,” and “bathing.”The mean time from commencing ChEI therapy to institutionalization for participants with EOAD (n=26) and LOAD (n=205), was 22.3 (18.7–25.8) vs. 19.3 (18.0–20.7) months (p=0.156), and the survival time in nursing homes was 4.6 (3.4–5.8) vs. 4.0 (3.6–4.4) years (p=0.352), which were similar between the groups. In a logistic regression model, NHP risk factors for all participants were solitary living, worse IADL capacity at baseline, and faster IADL decline during the study. In the EOAD cohort, more years of education and use of antihypertensives/cardiac therapy, were independent predictors of a lower risk of institutionalization. Conclusion: The present study highlights the clinical importance of functional evaluations for individuals with EOAD. Patients in the LOAD group had significantly worse functional ability at baseline than those with EOAD; however, younger patients deteriorated faster in some individual items. Performance in IADL, but not cognitive ability, predicted NHP in both groups. A similar need for NHP and survival time in nursing homes might be expected for both groups, which is important knowledge for community-based services. Among patients with EOAD, higher education or antihypertensives/cardiac therapy might predict less risk of institutionalization. (Less)