Treating the Behavioral and Psychological Burdens of Alzheimer’s Disease
By Aaron Pinkhasov, MD Chairman, Department of Behavioral Health NYU Winthrop Hospital
Alzheimer’s disease (AD), is a chronic, slowly progressive disorder that involves impairment of cognitive functions, speech, personality and executive function.1
While it is estimated that over 5 million Americans are affected by AD, it also places a profound burden on the lives of approximately 15-20 million caregivers.2 They must deal with the impact of this devastating disease on the patient, as well as the stress their responsibilities place on their own health. Much of a caregiver’s burden stems from having to deal with the AD patient’s difficult-to-manage and heartbreaking behaviors.
The non-cognitive behavioral and psychiatric disturbances resulting from AD were described under the umbrella of Behavioral and Psychological Symptoms of Dementia (BPSD) by The International Psychogeriatric Association in 1996. BPSD typically presents in the later stages of AD and is seen in up to 90% of patients during the course of this shattering illness.3
BPSD frequency increases as dementia intensifies. It is more prevalent in long-term care facilities and associated with elderly abuse risk, caregiver stress, increased duration of hospitalization, greater likelihood of nursing home placement and substantial financial burden. Symptoms may include verbal and physical aggression, psychomotor agitation, motor and verbal perseveration, anxiety, depression, disinhibition, delusions, hallucinations, sleep disturbances, wandering and hoarding.5
First Rule Out Delirium
It is important to distinguish BPSD from delirium. AD patients are especially at risk for delirium due to acute medical problems and/or medications. While BPSD and delirium symptoms overlap considerably, acute presentation and resolution of symptoms with elimination of the underlying medical cause is indicative of delirium.
Depression in Alzheimer’s Disease
The incidence of depression in AD patients runs as high as 43%, often occurring concomitantly with agitation, anxiety and irritability. However, due to expressive difficulties, AD patients rarely report typical depression symptoms. Instead, they may get preoccupied with somatic symptoms, pessimistic thoughts, worries, apathy and loss of self-esteem. Considering the side effect profile, selective serotonin reuptake inhibitors (SSRI) — but not tricyclic antidepressants (TCA) or monoamine oxidase inhibitors (MAOi) — should be employed. Recent studies have revealed a limited role of conventional antidepressants in depressed AD patients, indicating alterations in glutamatergic transmission and the potential need for a different psychopharmacological approach. 9
Psychosis in Alzheimer’s Disease
Psychosis occurs in up to 50% of AD patients, usually presenting with delusions and hallucinations. Common delusions include suspicion of theft, infidelity, abandonment and persecution. Rapid cognitive decline is more likely to be associated with the onset of psychosis in AD, which highly correlates with incidence of depression, agitation and care-giver burden. 10
BPSD Treatment Options
Treatment options for managing BPSD involve psychopharmacological and non-psychopharmacological approaches. Due to the associated risk and limited efficacy of psychotropic medications in BPSD patients, it is important to try a non-pharmacological approach before prescribing medications. While the FDA has not approved medication for the management of BPSD, treatment is largely based upon symptoms, and may include the use of cholinesterase inhibitors, anti-psychotics, antidepressants and mood stabilizers. 11,12
Since cholinergic deficiency appears to underlie the development of BPSD, cholinesterase inhibitors are used in an attempt to delay onset and to ameliorate AD-related behavioral disturbances. Memantine, alone or in combination with acetylcholinesterase inhibitors, has also been shown to have some anti-agitation effects. 13
Recent reviews of the use of pharmacological interventions for BPSD highlight the potential risks of medications, particularly antipsychotics. Due to increased incidence of strokes, pneumonia, cardiovascular events and overall mortality in elderly demented patients treated with antipsychotics, it is crucial to assess, discuss and document risks and benefits of antipsychotics. 14,15
The American Geriatric Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults discourage use of medications with strong anti- cholinergic side effects, such
as antihistamines, TCAs and antispasmodics, as well as benzodiazepine and non-ben- zodoazepine hypnotics in this population. 16 Even though some suggest the use of low-dose valproic acid (VPA) in AD agitation, 17 VPA has not been shown to delay onset of agitation or psychosis in AD patients. Rather, it has been associated with somnolence, gait disturbance and overall functional decline. 18
Non-Pharmacological Approach to Managing BPSD
Growing evidence suggests that comprehensive non-pharmacological approaches, grounded in maintaining the physical and emotional comfort of the individual, may be more appropriate. 11,15,19
Educating caregivers to address possible triggers of BPSD, such as discomfort, hunger, thirst, over/under stimulation and fear of abandonment, will ensure implementation of the “unmet needs” model. Unfortunately, inadequate resources, secondary to the cost and/or lack of skill sets, often lead to use of off-label psychotropic medications. 21
In order to prevent and reduce caregiver burnout, specialized training in the person-centered approach is required to improve empathy and resiliency toward the disease-related behaviors of people with AD. 22
- Butler R, Radhakrishnan R. Dementia. BMJClinEvid 2012 Sep10;2012. pii:1001. PubMed PMID:23870856.
- http://www.alzfdn.org/AboutAlzheimers/statis- tics_pr.html.
- Finkel SI, Costa e Silva J, Cohen G, et al. Behavioral and psychological signs and symp- toms of dementia: a consensus statement on current knowledge and implications for research and treatment. IntPsychogeriatr 1996;8(Suppl.3):497–500.
- Jost BC, Grossberg GT. The evolution of psy- chiatric symptoms in Alzheimer’s disease: a natural history study. JAGS 1996;44(9):1078- 1081. PubMed PMID: 8790235.
- Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. FrNeuro 2012;3:73. doi:10.3389/fneur.2012.00073.
- Burke A. Pathophysiology of behavioral and psychological disturbances in dementia. In:McNamara P, ed. Vol. 2:Science and Biology. Santa Barbara, CA; ABC-CLIO, LLC; 2011:135-158.
- Hirono N, Mega MS, Dinov ID, et al. Left fron- totemporal hypoperfusion is associated with aggression in patients with dementia. ArchNeurol 2000;57:861-866.
- Geschwind D, Nestler EJ. Neurodegenerative dementias: connecting psychiatry and neurolo- gy through a shared neurobiology. BiolPsychiatry 2014;75(7):518-519. doi: 10.1016/j.biopsych.2014.02.007. PubMed PMID:24629667.
- Khundakar AA, Thomas AJ. Neuropathology of depression in Alzheimer’s disease: current knowledge and the potential for new treat- ments. JAlzDis 2015;44(1):27-41. doi: 10.3233/JAD-148003. PubMed PMID: 25208623.
- Zahodne LB, Ornstein K, Cosentino S, et al. Longitudinal relationships between Alzheimer disease progression and psychosis, depressed mood, and agitation/aggression. AmJGerPsychiatry 2015;23(2):130-40. doi:10.1016/j.jagp.2013.03.014. PubMed PMID: 23871118.
- American Geriatrics Society; American Association for Geriatric Psychiatry. Consensus statement on improving the quality of mental health care in U.S. nursing homes: management of depression and behavioral symptoms associ- ated with dementia. JAGS 2003;51(9):1287-1298.
- Conn DK, Gibson M, Feldman S, et al. National guidelines for seniors mental health: the assess- ment and treatment of mental health issues in long-term care homes (focus on mood and behaviour symptoms). CanJGeriatr 2006;9:S59–S64.
- Alexopoulos GS, Streim J, Carpenter D, et al. Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. Using antipsychotic agents in older patients. JClinPsychiatry 2004;65(suppl 2):5-10.
- Ballard CG, Waite J, Birks J. Atypical antipsy- chotics for aggression and psychosis in Alzheimer’s disease: review. 2006 Cochrane Database Syst Rev 1.
- Azermai M, Petrovic M, Elseviers MM, et al. Systematic appraisal of dementia guidelines for the management of behavioural and psycholog- ical symptoms. AgeingResRev 2012;11(1):78-86. doi:10.1016/j.arr.2011.07.002.
- https://www.dcri.org/trial-participation/the- beers-list/
- Dolder C, McKinsey J. Low-dose divalproex in agitated patients with Alzheimer’s disease. JPsychPract 2010;16(1):63-67. doi: 10.1097/01.pra.0000367781.26507.86.