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Current Clinical Perspective on the Management of Behavioral Disturbances in Dementia

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The DSM-V diagnosis of Major Neurocognitive Disorder, which largely corresponds to dementia, requires substantial impairment to be present in one or more cognitive domains as memory, attention, and language, etc. The impairment must be sufficient to interfere with the patient’s independence in performing everyday activities.

According to Alzheimer’s Foundation, more than 6.5 million Americans over 65 live with impairing symptoms of the neurocognitive disorder. The number is doubling, reaching an estimated 13 million by 2050. The average cost of treatment was over $350 million in 2021 and is expected to triple by 2050. Caregiver fatigue carries an undoubtedly paramount psychological burden alongside the financial cost of lost wages.

While the most prevalent subtype of neurocognitive disorder is Alzheimer’s dementia (60-80%), the most common presentation is a mixed form of vascular or other neurodegenerative culprits. About 25% of patients living with Parkinson’s disease develop symptoms of neurocognitive disorder later in the course of their illness.

There’s a growing clinical investment in understanding the risk factors in preclinical stages and recognizing the earlier signs of mild cognitive impairment. A healthy lifestyle, including diet, exercise, and controlling risk factors such as hypertension and diabetes mellitus, mitigate the illness.

Two main dementia treatment target domains of clinical symptoms are memory impairment and behavioral disturbances. The behavioral disturbances that often accompany the cognitive impairment include mood symptoms, irritability, anxiety, agitation, and even delusions and perceptual disturbances. 

Antidepressants class of selective serotonin reuptake inhibitors have been studied in numerous trials showing modest effects in alleviating some of those symptoms. Antipsychotics have also been trialed with intermittent effects especially with psychotic symptoms. However, they should be carefully used given their various side effects, including a black box warning for increased mortality risk largely related to metabolic and cardiac risks. On smaller scales, mood stabilizers, atypical antidepressants and anxiolytics have shown inconsistent results.

While the FDA approved several medications to delay the progression of memory impairment, the domain of behavioral disturbances continues to rely mainly on clinicians’ judgment and off-label use of psychotropic medications. However, earlier this month, the FDA approved the very first drug — brexpiprazole — for the treatment of agitation in dementia. The expedited FDA review noted reduction of agitation by about 31% in the study subjects when compared to placebo groups of phase 3 trials.

A cornerstone for the management hinges upon tailored plans that are centralized around the individual. In many parts of the United States, clinicians are defining various models of multidisciplinary collaborative care among medical specialties to deliver personalized and encompassing treatment plans. Through collaborative care, treatments transcend to include the patients’ environments, diet, sleep, medical comorbidities and caregivers’ support. Patients and families continue to help us — clinicians — understand their clinical and social needs and to deliver safe and effective healthcare.

Dr. Botros has no conflicts of interest to report.

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