Long-term progression of Alzheimer's disease in patients under antidementia drugs
ABSTRACT Patients with Alzheimer's disease (AD), even in the presence of symptomatic relief from medical intervention, face a persistent worsening of cognitive decline and performance in activities of daily living. Data regarding the long-term disease progression outside of therapeutic trials are lacking. We examined the effects of standard of care for AD patients on the prognosis of the disease in a real-life study over a 4-year period.
A total of 686 patients with mild-moderate AD were enrolled in 16 memory clinics (REseau sur la maladie d' Alzheimer FRançais [REAL.FR] cohort) and followed up twice annually with tools used in therapeutic trials (Mini-Mental Status Examination, Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-cog]: cognitive function, Clinical Dementia Rating: dementia severity, Activity of Daily Living [ADL]: incapacities, NeuroPsychiatric Inventory: neuropsychiatric symptom).
More than 90% of the patients used AD-specific medication over 4 years. Patients lost on average 2.4 points per year on the Mini-Mental Status Examination and gained 4.5 points on the ADAS-cog. ADL and NeuroPsychiatric Inventory scores became significantly worse over time. Incidence of incapacities for ADL and worsening of neuropsychiatric symptoms were 52.5 (95% confidence interval [CI]: 47.7-57.4) and 51.1 (95% CI: 46.2-56.1), respectively. Rates of mortality and institutionalization were 7.4 (95% CI: 6.2-8.5) and 13.4 (95% CI: 11.7-15.1). In all, 17% of patients in mild stage at baseline (Clinical Dementia Rating = 0.5) did not experience a major event (functional disabilities, neuropsychiatric symptoms, or death) over a 4-year period.
As compared with previous surveys, the current study shows slower rates of decline in AD patients. The present data also underline the high level of variability of disease progression among AD patients. Outcome measures commonly used in clinical trials will need to take into account the recent changes in the prognosis of the disease.
[Show abstract] [Hide abstract]
ABSTRACT: Objectives: To describe the sequence of basic activities of daily living (ADL) loss to determine whether there is a hierarchical structure of ADL in dementia in two epidemiological prospective studies: the Paquid study and the Three City Study (3C). Design: Two prospective population-based cohort studies: Paquid (over 22 years of follow-up) and 3C (over 10 years of follow-up). Setting: Paquid Study, Gironde, Dordogne, France; The Three Cities Study, Bordeaux, Montpellier, Dijon, France. Main outcomes measures: We analyzed four ADL of the Katz scale: bathing, dressing, transferring and feeding. The a priori hierarchical relationship of the 4 activities tested was 1) no ADL-disability at all four activities; 2) moderate ADL-disability, or disability at bathing and/or dressing (and no disability in transferring nor feeding); and 3) severe ADL-disability, or disability in bathing and/or dressing and transferring and/or feeding. We performed a Guttman scale analysis to establish the hierarchical properties scale. Results: In total, 845 incident cases of dementia were included, among which 838 cases (99.2%) were without any missing data for ADL. Upon diagnosis of dementia, 564 subjects (67.3%) had no ADL-disability, 236 (26.2%) had moderate ADL-disability, and 38 subjects (4.5%) had severe disability. The a priori hierarchy was respected with non-discordance. Conclusion: We defined 3 simple relevant stages of ADL functional decline in dementia that would be easy to collect in clinical practice: stage 1, subjects with no major ADL disabilities; stage 2, subjects with complete disability in bathing and/or dressing; and stage 3, subjects with complete disability in all 4 tasks.The Journal of Nutrition Health and Aging 08/2014; 18(7):698-704. DOI:10.1007/s12603-014-0028-0 · 2.66 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.Molecular Psychiatry advance online publication, 6 May 2014; doi:10.1038/mp.2014.32.Molecular Psychiatry 05/2014; 20(3). DOI:10.1038/mp.2014.32 · 15.15 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Measuring and predicting Alzheimer's disease (AD) progression is important in order to adjust treatment and allocate care resources. We aimed to identify a combination of subtests from the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) that best correlated with AD progression in follow-up as well as to predict AD progression. A total of 236 participants with very mild [Clinical Dementia Rating (CDR) = 0.5] or mild AD (CDR = 1.0) at baseline were followed up for 3 years. The CERAD-NB and Mini-Mental State Examination (MMSE) were used to assess cognition, and the CDR scale sum of boxes (CDR-sb) was employed to evaluate AD progression. Generalized estimating equations were used to develop models to predict and follow up disease progression. Performance declined on all CERAD-NB subtests. The ability of the separate subtests to distinguish between groups (baseline CDR = 0.5 or 1.0) diminished during follow-up. The best combination of subtests that explained 62% of CDR-sb variance in follow-up included verbal fluency, constructional praxis, the clock drawing test, and the MMSE. Baseline values of the same combination predicted 37% of the CDR-sb change. A short version of the CERAD-NB subtests provides a promising and time-efficient alternative for measuring cognitive deterioration during AD follow-up. Although the initial signs of AD include memory difficulties, it may be useful to assess non-memory tasks in follow-up.