Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

Background: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. Objectives: The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer’s disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD, or FTD and BD or (hypo) mania have been included. Results: Manic symptoms seem to be associated to disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincide with or precede cognitive impairment in FTD. Overall, mood stabilizers, and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert neuroprotective activity in patients with AD. Conclusion: Prevalence, course, and characteristics of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.