Long-term progression of Alzheimer's disease in patients under antidementia drugs

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.