Five-Year Outcome of Cholinergic Treatment of Alzheimer’s Disease: Early Response Predicts Prolonged Time until Nursing Home Placement, but Does Not Alter Life Expectancy

Background/Aims: Factors including rate of disease progression, different aspects of cholinesterase inhibitor (ChEI) treatment, and use of community-based services might affect the longitudinal outcome of Alzheimer's disease (AD). Whether these factors alter life expectancy in AD is unclear. We therefore examined the association between long-term ChEI therapy and survival. Methods: The present study included 1,021 patients with a clinical diagnosis of AD and a Mini-Mental State Examination score of 10-26 at baseline from a 3-year, prospective, multicenter study of ChEI therapy in clinical practice. The relationship of potential predictors with mortality was analyzed using Cox regression models. Results: After up to 16 years of follow-up, 841 (82%) of the participants had died. In the Alzheimer's Disease Assessment Scale-cognitive subscale, a mean decline of ≥4 points/year or ≥2 points/year on the Physical Self-Maintenance Scale was a risk factor for an earlier death. In the multivariate models, longer survival was associated with higher ChEI dose and longer duration of treatment. Users of community-based services at baseline exhibited a 1-year shorter mean life expectancy than nonusers. Conclusion: A longer survival time can be anticipated for AD patients with slower deterioration who receive and tolerate higher ChEI doses and a longer duration of treatment.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

Wattmo¹,

Londos²,

Minthon³

2015

“…The fact that such a large fraction of patients in both diagnostic groups was treated with cholinesterase inhibitors should be taken into consideration since this has been shown to alter the cognitive progression in AD [32,38,39,40,41] and is most likely to do so in DLB as well [42,43,44]. …”

Section: Discussionmentioning

confidence: 99%

Differences in Survival between Patients with Dementia with Lewy Bodies and Patients with Alzheimer's Disease - Measured from a Fixed Cognitive Level

Stubendorff

Hansson

Minthon

et al. 2011

Introduction: The aim of this study was to compare survival in patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB). Since anamnestic and retrospective information about disease duration are unreliable variables, we measured survival from a fixed cognitive level. Methods: Survival time was measured from the reported disease onset, from the time of diagnosis, from Mini-Mental State Examination (MMSE) 20 ± 1, and from MMSE 17 ± 1. Results: Survival time was significantly shorter in the DLB group compared to the AD group both from the time of diagnosis and from the cognitive levels of 20 and 17 on the MMSE. There was no difference in survival when measured from the reported disease onset. Discussion: Our findings indicate that DLB patients have a more malignant clinical course. Our method of investigating survival in a cognitively homogenous population may gain scientific power. Reliable methods to predict survival and the clinical course are of great value for patients, caregivers, doctors, and society.

“…The APOE genotype was also determined in a part of AD patients included in a fi ve-year outcome study of tacrine effect on AD and the results did not demonstrate a signifi cant difference in the rate of mortality or response to treatment between 4 carriers versus non-carriers with AD [17] .…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ε4 Allele Differentiates the Clinical Response to Donepezil in Alzheimer’s Disease

Bizzarro¹,

Marra²,

Acciarri³

et al. 2005

The existence of an association between apolipoprotein E (APOE) and Alzheimer’s disease (AD) has been reported in several studies. The possession of an ApoE ε4 allele is now considered a genetic risk factor for sporadic AD. There has been a growing agreement about the role exerted by the ApoE ε4 allele on the neuropsychological profile and the rate of cognitive decline in AD patients. However, a more controversial issue remains about a possible influence of the APOE genotype on acetylcholinesterase inhibitor therapy response in AD patients. In order to address this issue, 81 patients diagnosed as having probable AD were evaluated by a complete neuropsychological test battery at the time of diagnosis (baseline) and after 12–16 months (retest). Patients were divided into two subgroups: (1) treated with donepezil at a dose of 5 mg once a day (n = 41) and (2) untreated (n = 40). Donepezil therapy was started after baseline evaluation. The APOE genotype was determined according to standardized procedures. We evaluated the possible effect of the APOE genotype on the neuropsychological tasks in relation to donepezil therapy. The statistical analysis of the results showed a global worsening of cognitive performances for all AD patients at the retest. Differences in the clinical outcome were analysed in the four subgroups of AD patients for each neuropsychological task. ApoE ε4 carriers/treated patients had improved or unchanged scores at retest evaluation for the following tasks: visual and verbal memory, visual attention and inductive reasoning and Mini Mental State Examination. These results indicate an effect of donepezil on specific cognitive domains (attention and memory) in the ApoE ε4 carriers with AD. This might suggest an early identification of AD patients carrying at least one ε4 allele as responders to donepezil therapy.