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A short yet reliable cognitive measure is needed that separates treatment and placebo for treatment trials for Alzheimer’s disease. Hence, we aimed to shorten the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) and test its use as an efficacy measure.
Methods
Secondary data analysis of participant-level data from five pivotal clinical trials of donepezil compared with placebo for Alzheimer’s disease (N = 2,198). Across all five trials, cognition was appraised using the original 11-item ADAS-Cog. Statistical analysis consisted of sample characterization, item response theory (IRT) to identify an ADAS-Cog short version, and mixed models for repeated-measures analysis to examine the effect sizes of ADAS-Cog change on the original and short versions in the placebo versus donepezil groups.
Results
Based on IRT, a short ADAS-Cog was developed with seven items and two response options. The original and short ADAS-Cog correlated at baseline and at weeks 12 and 24 at 0.7. Effect sizes based on mixed modeling showed that the short and original ADAS-Cog separated placebo and donepezil comparably (ADAS-Cog original ES = 0.33, 95% CI = 0.29, 0.40, ADAS-Cog short ES = 0.25, 95% CI =0.23, 0.34).
Conclusions
IRT identified a short ADAS-cog version that separated donepezil and placebo, suggesting its clinical potential for assessment and treatment monitoring.
Neuropsychiatric symptoms in major neurocognitive disorders have been strongly associated with suicidality.
Methods
The objectives were to explore suicide rates in degenerative neurocognitive disorders (DNDs), alcohol-related neurocognitive disorders (ARNDs), and traumatic brain injuries (TBIs). Patients who received these diagnoses between 1998 and 2015 (N = 231,817) were identified from nationwide registers, and their mortality was followed up until December 31, 2018. We calculated incidences of suicides per 100,000 person-years, types of suicides, and suicide rates compared with the general population (standardized mortality ratio [SMR]).
Results
During the follow-up, 0.3% (95% confidence interval [95% CI]: 0.2–0.5) of patients with DNDs, 1.1% (0.7–1.8) with ARNDs, and 1.0% (0.7–1.3) with TBIs committed suicide. Suicide mortality rate was higher in men (58.9, 51.3, to 67.4 per 100,000) than in women (9.8, 7.5, to 12.5 per 100,000). The highest suicide rate was in ARNDs (98.8, 65.1, to 143.8 per 100,000), followed by TBIs (82.0, 62.4, to 105.8 per 100,000), and DNDs (21.2, 18.3, to 24.5 per 100,000). The SMRs (95% CI) were 3.69 (2.53–5.38), 2.99 (2.31–3.86), and 1.31 (1.13–1.51), respectively, and no sex difference emerged. The most common cause of death was self-inflicted injury by hanging or drowning (12.4, 10.3, to 14.8 per 100,000).
Conclusions
Suicide rates were higher in all three patient groups than the general population. Suicide risk remained elevated for more than 10 years after diagnosis. The suicide methods were mostly violent.