Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer’s disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer’s disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0–4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4–10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points; 95% CI, 14.5–16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting.
Background and Objectives:ATN (β-Amyloid, Tau, Neurodegeneration) system categorizes individuals based on their core Alzheimer’s disease (AD) biomarkers. An important potential future use for ATN is therapeutic decision-making in clinical practice once disease-modifying treatments, e.g., anti-amyloid, become widely available. In this cross-sectional study, we applied ATN and estimated potential eligibility for anti-amyloid treatment in a real-life memory clinic with biomarker assessments integrated into the routine diagnostic procedure and all specialized resources available for the implementation of novel treatments.Methods:We included all consecutive patients at the Karolinska University Hospital Memory clinic in Solna, Stockholm, Sweden, who had their first diagnostic visit in April 2018–February 2021, informed consent for the clinic research database, and available clinical and biomarker (CSF, imaging) data. ATN classification was based on CSF Aβ42 (or Aβ42/40; A), CSF phosphorylated tau (T), and medial temporal lobe atrophy (N). For CSF markers, we applied laboratory cut-offs and data-driven cut-offs for comparison (determined with Gaussian mixture modelling). Anti-amyloid treatment eligibility was assessed following the published recommendations for aducanumab (AD dementia or MCI with no evidence of non-AD etiology, appropriate level of cognition, AD-consistent CSF profile).Results:Study population consisted of 410 patients (52% subjective cognitive impairment, 23% mild cognitive impairment MCI, 25% any dementia; age 59±7 years, 56% women). Regardless of biomarker cut-offs, most patients were A−T−N− (54–57%). A+ prevalence was 17–30% (higher with data-driven cut-offs). Up to 13% of all patients (27% of those with MCI and 28% of those with dementia) were potentially eligible for anti-amyloid treatment when AD-consistent CSF was defined as any A+ profile. When A+T+ profile was required, treatment was targeted more to the dementia than MCI stage (eligibility up to 14% in MCI, 22% in dementia). The opposite applied to earlier stage intervention (A+T−N−; eligibility up to 12% in MCI, 2% in dementia).Discussion:In a memory clinic setting with all necessary infrastructure and national guidelines in place for dementia diagnostic examination (“best-case scenario”), most patients did not meet the eligibility criteria for anti-amyloid treatment. Continuing the development of disease-modifying treatments with different mechanisms of action is a priority.
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