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Introduction: Neuropsychiatric symptoms (NPS) are common at all stages of Alzheimer disease (AD). Delusions in AD are associated with negative clinical consequences and may signal rapid disease progression. Hence, we sought to determine the prevalence of delusions in drug-naïve (no cholinesterase inhibitor or neuroleptic medications) AD patients., Methods: In this meta-analysis, a search of the EMBASE, MEDLINE, and PsycINFO databases was performed. We selected studies reporting delusion prevalence measured by the Neuropsychiatric Inventory (NPI) in drug-naïve AD patients. An aggregate delusion event rate with 95% confidence interval (CI) was calculated. The I 2 statistic was used to assess the magnitude of between-study heterogeneity. Single variable meta-regressions allowed examination of the effect of moderating factors and heterogeneity. Quantitative measures were used to appraise for publication bias., Results: We identified 6 studies with 591 participants allowing calculation of the aggregate delusional prevalence rate. Irrespective of dementia severity, the aggregate event rate for delusions was 29.1% (95% CI: 20-41%; I 2  = 84.59). No publication bias was observed., Conclusion: This meta-analysis calculates a 29.1% prevalence rate of delusions in AD patients. There is a trend towards increasing delusion prevalence in concordance with increasing severity of dementia. Given delusions are associated with poorer outcomes, the obtained prevalence should motivate clinicians to screen carefully for delusions. Current literature limitations warrant future studies, with sub-analyses on dementia severity, and other neurobiological factors known to influence the presence of delusions., (Copyright © 2017 John Wiley & Sons, Ltd.)

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

Background: Comorbid depression is a leading neuropsychiatric complication in the Alzheimer's disease (AD) syndrome. In 2011, diagnostic criteria for AD were revised to include neuropsychiatric symptoms. It has been proposed that adding an antidepressant to existing treatment for AD could provide relief for not only depressive but also cognitive symptoms., Objective: The aim was to quantitatively review published studies to examine the efficacy of selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) therapy for alleviation of comorbid, diagnosed depression as well as cognitive decline in AD., Methods: A search of electronic databases was performed. Studies were retained for analysis if SSRI/SNRI antidepressant therapy was compared with placebo among AD patients with comorbid depression. Effect-size (ES) estimates (Hedges' g) were calculated using Comprehensive Meta-Analysis software., Results: From 598 examined studies, 12 SSRI studies met the inclusion criteria, and from these, only six met all criteria, among which five reported sufficient and consistent data to be included in the meta-analysis. Within a random effect model, ES estimates of the first and second nested global analyses were non-significant, non-heterogeneous and small to null at the endpoint for depression, favouring SSRIs, -0.06 and -0.10, respectively (p > 0.05). The ES for global cognition as measured by the Mini-Mental State Examination was negligible (ES = 0.001)., Conclusions: Current evidence does not support the efficacy of SSRI treatment for symptoms of comorbid depression in AD. However, studies differed in terms of criteria for diagnosis of depression, the compound tested and outcome measures for depression. These factors could account for the lack of a clear benefit for depression.

Objective: To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology., Methods: We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology., Results: Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02)., Conclusion: While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.