Objective: To characterize the rate of cognitive decline in patients with mild-to-moderate Alzheimer’s disease (AD) who remain untreated and to evaluate the relationship between changes in cognition and changes in activities of daily living (ADL). The secondary objective was to investigate the effect on caregiver time of declining ADL in mild-to-moderate AD.
Design: Data from 2 previously conducted, 12-month, randomized, placebo-controlled studies (one in the United States, one international) of sabeluzole, a drug initially developed for AD but since discontinued, were reanalyzed. Individuals enrolled in the studies had a diagnosis of probable AD, baseline MMSE scores of 14 to 22, and no clinical evidence of another cause for cognitive impairment.
Materials and methods: Cognition was assessed using the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog), and ADL were assessed using the Disability Assessment for Dementia (DAD). Assessments were carried out at Months 6, 9, and 12, although no DAD assessment was conducted at Month 9 in the international study. A post hoc analysis also was performed in patients categorized as having mild AD (MMSE > 18) or moderate AD (MMSE £ 18) at baseline. As a secondary analysis, data were gathered on time spent by caregivers assisting patients with ADL.
Results: Baseline characteristics of patients receiving placebo in the 2 trials were similar, and therefore the 2 groups could be pooled for analysis. Patients receiving placebo experienced a significant and progressive decline in cognition over 12 months. Patients with moderate AD showed greater decline in ADAS-cog than those with mild AD. The observed rate of decline over 12 months in placebo-treated patients (5.6 ± 0.40 points) was comparable to that predicted by the equation of Stern et al (4.9 ± 0.12 points). Patients receiving placebo experienced a significant, progressive decline in ADL over 12 months, with moderate patients showing greater decline in DAD than those with mild AD. Patients with mild AD showed loss of instrumental AD, whereas both basic and instrumental AD were lost in patients with moderate disease. Cognitive decline was correlated with functional decline (r = –0.52), although correlations between individual ADAS-cog and DAD items were less strong. The amount of time that caregivers spent assisting with ADL increased from 33 hours every 2 weeks to 47 hours every 2 weeks.
Conclusions: There is a correlation between functional and cognitive decline. Declining functional ability leads to an increase in caregiver time. This study was the first to assess long-term cognitive deterioration in untreated AD using disease-specific, validated measures of cognition and daily function. The availability of these 12-month placebo data will allow the efficacy of AD treatments to be assessed more accurately in open-label trials.
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