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.
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ABSTRACT: The formation of the first Gerontopole in Toulouse was a response to a mission letter sent by French Ministers of Health on February 2007. The mission of the Toulouse Gerontopole is based around three major axes: 1) To facilitate the access of frail elderly people to innovative therapy and clinical research: the Gérontopôle set up the national network for clinical investigation into Alzheimer's disease (AD) funded through the CeNGEPS (National Centre For Management of Trials on Health Products) calls for proposals since July 2008. In addition, the Gérontopôle coordinates several national clinical trials with promising drugs with potential effect on the mechanisms and evolution of AD and actively participates in studies on biomarkers; 2) To develop health promotion actions and prevention trials for healthy elderly people, through the Institute of Aging: the Gérontopôle has implemented the GuidAge (Phase III trial concerning the efficiency of Ginkgo Biloba on the impact and delay of appearance of an Alzheimer type dementia) and MAPT (Multi-domain Alzheimer Preventive Trial) studies on prevention of AD and cognitive decline. It is curently working on the new generation of preventive trials based on biomarkers; 3) To develop clinical research for dependant elderly people, through the implementation of the REHPA research network including 240 nursing homes in France. In December 2009, additional grants were delivered by the French government to extend the three research axes for two more years, and establish a charter of quality for geriatric care in relation with the administration and relevant agencies.Journal of Alzheimer's disease: JAD 01/2012; 28(3):721-32. DOI:10.3233/JAD-2011-112202 · 4.15 Impact Factor
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ABSTRACT: Few studies have reported the risk of death related to Alzheimer's disease (AD) in large population-based cohorts. The objective of this study was to analyze the impact of AD on all-cause mortality in a nationwide sample of persons with AD. Community-dwelling persons with AD and an equal number of individually matched (age, gender, and region of residence) control persons without AD were identified from the registers of Social Insurance Institution of Finland at the end of 2005. Deaths in this sample (n = 56,041, mean age 79.7 years, 67.8% women) during a 57-month follow-up period were recorded. Using a nested case-control design, unadjusted and adjusted (cardiovascular disease, cancer, diabetes, and asthma and/or COPD) hazard ratios (HR) with 95% confidence intervals (CI) were computed using proportional hazards regression. The results were categorized according to age at death (<80, 80 to 89, ≥90 years) and duration of AD (≤3, 4 to 6, ≥7 years). The unadjusted HR for death associated with AD was 2.03 (95% CI: 1.97 to 2.09). The HR was highest in the youngest age category [HR = 3.46 (95% CI: 3.18 to 3.77)], and still significantly elevated in the oldest age category [HR = 1.50 (95% CI: 1.41 to 1.60)]. Comorbidity adjustments did not change the HRs, and even a short duration of AD (≤3 years) was associated with a significantly increased risk of death. In conclusion, AD was associated with an increased risk of death that was more pronounced at younger ages and existed even after a recent diagnosis of AD.Journal of Alzheimer's disease: JAD 08/2012; 33(1). DOI:10.3233/JAD-2012-120808 · 4.15 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the effects of caprylic triglyceride (CT) in patients with mild-to-moderate Alzheimer's disease (AD) in routine clinical practice via review of medical records and caregiver questionnaires. Participants were outpatients aged ≥50 years with a diagnosis of probable mild-to-moderate AD who had received CT for ≥6 months. The primary outcome was change from baseline in the patient's condition as rated by the treating physician using a physician's overall assessment. A total of 55 patients were included. The physician's overall assessment indicated that ~80% of patients who had CT added to ongoing pharmacotherapy were stable or improved. Mini-Mental State Examination scores also remained stable over 15 months of therapy (20.6 ± 3.0 at baseline and 20.1 ± 5.6 at follow-up, P = 0.5233, n = 27). Caregiver assessments indicated that most patients were stable or improved with respect to memory and ability to carry out activities of daily living. The most frequent adverse events with CT involved the gastrointestinal system. Results from this chart review indicate that addition of CT to pharmacotherapy was associated with stable disease or improvement over a follow-up period of 18.8 months.Neuropsychiatric Disease and Treatment 10/2013; 9:1619-27. DOI:10.2147/NDT.S52331 · 2.15 Impact Factor