Abstract
BackgroundA varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer’s disease (AD). Whether the individual-specific response, specific ChEI agent or dose affects mortality is unclear. We aimed to examine the relationship between the 6-month response to ChEI and lifespan.MethodsSix hundred and eighty-one deceased patients with a clinical AD diagnosis and a Mini-Mental State Examination (MMSE) score of 10–26 at the start of ChEI therapy (baseline) were included in a prospective, observational, multicentre study in clinical practice. At baseline and after 6 months of treatment, the participants were assessed using the MMSE, the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician’s Interview-Based Impression of Change (CIBIC), the Instrumental Activities of Daily Living (IADL) scale, and the Physical Self-Maintenance Scale (PSMS). The individuals’ socio-demographic characteristics, ChEI dose, and date of death were recorded. Responses to ChEI and the association of possible risk factors with survival were analysed using general linear models.ResultsA longer lifespan (mean of 0.5 years) was observed among the improved/unchanged patients, as measured by MMSE or CIBIC score, but not by ADAS-cog score, after 6 months of ChEI therapy. In the multivariate models, increased survival time was independently related to a better 6-month response in MMSE, CIBIC, IADL, and PSMS scores, female sex, no antihypertensive/cardiac or antidiabetic therapy, younger age, lower education, milder disease stage at baseline, and higher ChEI dose. Apolipoprotein E genotype did not affect mortality significantly. The patients who received a higher ChEI dose during the first 6 months had a mean lifespan after baseline that was 15 months longer than that of those who received a lower dose.ConclusionsA better short-term response to ChEI might prolong survival in naturalistic AD patients. In individuals who received and tolerated higher ChEI doses, a longer lifespan can be expected.
Highlights
A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer’s disease (AD)
A recent study from our group that compared the Swedish Alzheimer Treatment Study (SATS) participants with untreated AD cohorts found no difference between these groups in patients aged < 85 years; a longer lifespan was observed among the ChEI-treated oldest old participants [5]
A significant association between a higher dose of ChEI and a lower amount of home help services [45], and delays in the need for nursing home placement [28,46], has been reported. These results show that a higher ChEI dose would be beneficial as long as the individuals can tolerate this medication
Summary
A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer’s disease (AD). Whether the individual-specific response, specific ChEI agent or dose affects mortality is unclear. Multiple placebo-controlled randomised clinical trials have shown modest responses after 6 months of ChEI therapy regarding cognition, global performance, and ADL [9]. Not every patient with AD benefits from ChEI treatment, because the level of response varies among individuals. In some AD studies, a more positive cognitive response to ChEI was observed in participants with a faster disease progression [10] or lower cognitive ability [11,12] and in patients taking larger doses of ChEIs [12,13]. Whether shortterm response to ChEI alters the survival time in AD is not clear
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