Affiliations: [a]
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| [b]
The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
Correspondence:
[*]
Correspondence to: Milap A. Nowrangi, MD, Department of Psychiatry, Johns Hopkins Bayview Medical Center, 5300 Alpha Commons Drive, 4th Floor, Baltimore, MD 21224, USA. Tel.: +1 410 550 2294; Fax: +1 410 550 1407; E-mail: [email protected].
Abstract: Background:Despite the burden on patients and caregivers, there are no approved therapies for the neuropsychiatric symptoms of Alzheimer’s disease (NPS-AD). This is likely due to an incomplete understanding of the underlying mechanisms. Objective:To review the neurobiological mechanisms of NPS-AD, including depression, psychosis, and agitation. Methods:Understanding that genetic encoding gives rise to the function of neural circuits specific to behavior, we review the genetics and neuroimaging literature to better understand the biological underpinnings of depression, psychosis, and agitation. Results:We found that mechanisms involving monoaminergic biosynthesis and function are likely key elements of NPS-AD and while current treatment approaches are in line with this, the lack of effectiveness may be due to contributions from additional mechanisms including neurodegenerative, vascular, inflammatory, and immunologic pathways. Conclusion:Within an anatomic-genetic framework, development of novel effective biological targets may engage targets within these pathways but will require a better understanding of the heterogeneity in NPS-AD.
