Common neuropsychiatric symptoms of Alzheimer’s disease

Neuropsychiatric symptoms (NPS) affect approximately 97% of patients with AD,⁷ and are associated with impairments in daily function, poor quality of life, earlier institutionalization, accelerated progression of cognitive decline, and caregiver stress.^7-10 The most common NPS are apathy and depression.¹ Depression is common during the MCI stage and is a predictor of progression from normal cognition to MCI, and from MCI to dementia.¹

Another common NPS of AD with limited available treatment is sleep disturbance, which impacts cognition, behaviour and the quality of life of the patient and caregiver.^11,12 These disturbances may occur independently of and alongside depression.¹ Suvorexant, which is approved for insomnia in the US, has had successful results in the treatment of insomnia in AD.¹³It is important that when treating patients with AD, the impact of NPS on the patients’ quality of life should not be overlooked.¹ However, there is a need for additional research and the development of assessment tools for depression in the geriatric population.¹

The most active research area in drug development for neuropsychiatric symptoms in AD is the treatment of agitation.² In 2023, brexpiprazole received FDA approval for the treatment of agitation associated with dementia due to Alzheimer’s disease.³ Other drugs such as dextromethorphan/quinidine and AXS-05 (dextromethorphan/bupropion) have shown promising results for the treatment of agitation in Alzheimer’s dementia.^4,5 Disease-modifying and symptomatic therapies are both needed to improve the outcomes of patients with AD continuum disorders.¹¹ It is likely that future treatment plans will incorporate both types of therapy to maximize patient benefit.¹¹

References:
1. Burke AD, Goldfarb D, Bollam P, Khokher S. Diagnosing and treating depression in patients with Alzheimer’s disease. Neurol Ther 2019; 8 (2): 325–350.

2. Sano M, Cummings J, Auer S, et al. Agitation in cognitive disorders: progress in the International Psychogeriatric Association consensus clinical and research definition. Int Psychogeriatr 2023: 1–13.

3. Nørgaard A, Jensen-Dahm C, Wimberley T, et al. Effect of antipsychotics on mortality risk in patients with dementia with and without comorbidities. J Am Geriatr Soc 2022; 70 (4): 1169–1179.

4. APA Work Group on Alzheimer’s Disease and other Dementias; Rabins PV, Blacker D, Rovner BW, et al; Steering Committee on Practice Guidelines; McIntyre JS, Charles SC, Anzia DJ, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry 2007; 164 (12 Suppl): 5–56.

5. Richardson K, Loke YK, Fox C, et al. Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study. BMC Med 2020; 18 (1): 351.

6. Cardinali DP, Brown GM, Pandi-Perumal SR. Melatonin’s benefits and risks as a therapy for sleep disturbances in the elderly: current insights. Nat Sci Sleep 2022; 14: 1843–1855.

7. Steinberg M, Shao H, Zandi P, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 2008; 23 (2): 170–177.

8. Lyketsos CG, Carrillo MC, Ryan JM, et al. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimers Dement 2011; 7 (5): 532–539.

9. Taragano FE, Allegri RF, Krupitzki H, et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry 2009; 70 (4): 584–592.

10. Allegri RF, Sarasola D, Serrano CM, et al. Neuropsychiatric symptoms as a predictor of caregiver burden in Alzheimer’s disease. Neuropsychiatr Dis Treat 2006; 2 (1): 105–110.

11. Cummings J. New approaches to symptomatic treatments for Alzheimer’s disease. Mol Neurodegener 2021; 16 (1): 2.

12. Borges CR, Poyares D, Piovezan R, et al. Alzheimer’s disease and sleep disturbances: a review. Arq Neuropsiquiatr 2019; 77 (11): 815–824.