Cognitive impairment is common in individuals presenting to alcohol and other drug (AOD) settings and the presence of biopsychosocial complexity and health inequities can complicate the experience of symptoms and access to treatment services. A challenge for neuropsychologists in these settings is to evaluate the likely individual contribution of these factors to cognition when providing an opinion regarding diagnoses such as acquired brain injury (ABI). This study therefore aimed to identify predictors of cognitive functioning in AOD clients attending for neuropsychological assessment.

Clinical data from 200 clients with AOD histories who attended for assessment between 2014 and 2018 were analysed and a series of multiple regressions were conducted to explore predictors of cognitive impairment including demographic, diagnostic, substance use, medication, and mental health variables.

Regression modelling identified age, gender, years of education, age of first use, days of abstinence, sedative load, emotional distress and diagnoses of ABI and developmental disorders as contributing to aspects of neuropsychological functioning. Significant models were obtained for verbal intellectual functioning (Adj R2 = 0.19), nonverbal intellectual functioning (Adj R2 = 0.10), information processing speed (Adj R2 = 0.20), working memory (Adj R2 = 0.05), verbal recall (Adj R2 = 0.08), visual recall (Adj R2 = 0.22), divided attention (Adj R2 = 0.14), and cognitive inhibition (Adj R2 = 0.07).

These findings highlight the importance of careful provision of diagnoses in clients with AOD histories who have high levels of unmet clinical needs. They demonstrate the interaction of premorbid and potentially modifiable comorbid factors such as emotional distress and prescription medication on cognition. Ensuring that modifiable risk factors for cognitive impairment are managed may reduce experiences of cognitive impairment and improve diagnostic clarity.

Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).

In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.

Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.

We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.