Abstract: Neurocognitive impairment due to Alzheimer’s disease (previously termed Alzheimer’s dementia) (AD) is the most common form of cognitive impairment worldwide. Given the anticipated increase in the population aged 65 and over, the prevalence of persons with AD is expected to increase exponentially during the next 30 years. Noncognitive neuropsychiatric symptoms (NPS) commonly occur in AD and are associated with adverse outcomes for patients and their caregivers. This review summarizes randomized, controlled trials (RCTs) published between 2004 and 2014 with a primary outcome measure of change in symptom severity for NPS in AD. Of the 388 articles initially identified through a literature search, 33 trials met inclusion criteria. Fifteen of these studies had agitation/aggression as a targeted symptom. Twenty-eight evaluated pharmacologic treatments, including psychotropics, cognitive enhancers, stimulants, and nutraceuticals. Nonpharmacologic interventions included bright light, music, exercise, and cognitive-stimulation therapies. Among the pharmacologic interventions, modest efficacy was reported with aripiprazole, citalopram, trazodone, methylphenidate, and scheduled analgesics. Significant reduction in symptom severity was reported with nearly all the nonpharmacologic interventions. Variations in methodology such as inclusion criteria, study setting, and outcome measures limit the generalizability of these results. Barriers to the implementation of nonpharmacologic interventions in clinical settings include resource and training limitations. Electroconvulsive therapy and dronabinol are promising as emerging treatment strategies. Randomized clinical trials are needed in order to validate the utility of electroconvulsive therapy and dronabinol, including where and with whom these interventions will prove most valuable.
From the Sheppard Pratt Health System, Neuropsychiatry Program, Baltimore, MD (Dr. McClam); Johns Hopkins Bayview Medical Center, Division of Geriatric Psychiatry and Neuropsychiatry, Baltimore, MD (Drs. Marano, Rosenberg, and Lyketsos).
Supported, in part, by National Institute on Aging grant nos. R01 AG039384 (Dr. Rosenberg) and P50 AG005146 (to the Johns Hopkins Alzheimer’s Disease Research Center; Dr. Lyketsos).
Original manuscript received 25 April 2014; revised manuscript received 1 April 2015, accepted for publication subject to revision 3 May 2015; revised manuscript received 3 June 2015.
Correspondence: Tamela D. McClam, MD, Neuropsychiatry Program at Sheppard Pratt, 6501 N. Charles St, Gibson Bldg., Suite 100, Towson, MD 21204. Email: firstname.lastname@example.org