Addressing Alzheimer’s: A pragmatic approach

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Applied Evidence

Addressing Alzheimer’s: A pragmatic approach

J Fam Pract. 2015 January;64(1):10-18

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References

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2, 2014.

11. Jack CR, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207-216.

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13. Centers for Medicare and Medicaid Services. National coverage determination (NCD) for FDG PET for dementia and neurodegenerative diseases (220.6.13). Centers for Medicare and Medicaid Services Web site. Available at: http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=288&ncdver=3&bc=BAABAAAAAAAA&. Accessed December 2, 2014.

14. Albert MS, DeKosky ST, Ruckson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270-179.

15. Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive impairment to dementia—meta-analysis of 41 robust inception studies. Acta Psychiatr Scand. 2009;119:252-265.

16. Farias ST, Mungas D, Reed BR, et al. Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts. Arch Neurol. 2009;66:1151-1157.

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18. Ngo-Metzger Q, August KJ, Srinivasan M, et al. End-of-life care: guidelines for patient-centered communication. Am Fam Physician. 2008;77:167-174.

19. Sayegh P, Knight BG. Cross-cultural differences in dementia: the Sociocultural Health Belief Model. Int Psychogeriatr. 2013;25:517-530.

20. McDaniel SH, Campbell TL, Hepworth J, et al. Family-Oriented Primary Care. 2nd ed. New York, NY: Springer; 2005.

21. Bensadon BA, Odenheimer GL. Current management decisions in mild cognitive impairment. Clin Geriatr Med. 2013:29;847-871.

22. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;9:CD009132.

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25. Fillit HM, Doody RS, Binaso K, et al. Recommendations for best practices in the treatment of Alzheimer’s disease in managed care. Am J Geriatr Pharmacother. 2006;4(suppl A):S9-S24;quiz S25-S28.

26. Schneider LS, Tariot PN, Dagerman KS, et al; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355:1525-1538.

27. US Food and Drug Administration. Public health advisory: Deaths with antipsychotics in elderly patients with behavioral disturbances. US Food and Drug Administration Web site. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm053171.htm. Published April 11, 2005. Updated August 16, 2013. Accessed December 2, 2014.

28. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616-631.

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30. Huckans M, Hutson L, Twamley E, et al. Efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) in older adults: working toward a theoretical model and evidence-based interventions. Neuropsychol Rev. 2013;23:63-80.

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32. McLaren AN, Lamantia MA, Callahan CM. Systematic review of non-pharmacologic interventions to delay functional decline in community-dwelling patients with dementia. Aging Ment Health. 2013;17:655-666.

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TABLE 2

AD, Alzheimer’s disease; NIA, National Institute on Aging.
Resources for newly diagnosed patients and families
Issue	Resources
Education	Alzheimer’s and Dementia Caregiver Center http://www.alz.org/care/overview.asp NIA Alzheimer’s Disease Education and Referral Center http://www.nia.nih.gov/alzheimers/
Planning (medical, financial, legal)/benefits	AARP Caregiving Resource Center http://www.aarp.org/home-family/caregiving Alzheimer’s Association Alzheimer’s Navigator https://www.alzheimersnavigator.org/ National Council on Aging Benefits Checkup https://www.benefitscheckup.org/
Safety	Association for Driver Rehabilitation Specialists: Driving and Alzheimer’s/Dementia https://c.ymcdn.com/sites/www.aded.net/resource/resmgr/fact_Sheets/ADED_alzheimers-Dementia_fac.pdf NIA’s Home Safety for People with Alzheimer’s booklet http://www.nia.nih.gov/alzheimers/publication/home-safety-people-alzheimers-disease
Support	Caregiver Action Network http://caregiveraction.org/

Drugs address cognitive and behavioral function

No current treatments  can cure  or significantly alter the progression of AD, but 2 classes of medications are used to improve cognitive function. No currently available treatments can cure or significantly alter the progression of AD, but 2 classes of medications are used in an attempt to improve cognitive function. One is cholinesterase inhibitors (ChEIs), which potentiate acetylcholine synaptic transmission. The other is N-methyl-D-aspartate (NMDA) glutamate receptor blockers. Other classes of drugs are sometimes used to treat behavioral symptoms of dementia, such as agitation, aggression, mood disorders, and psychosis (eg, delusions and hallucinations).

Cognitive function. Results from studies of pharmacologic management of MCI vary widely, but recent reviews have found no convincing evidence that either ChEIs or NMDA receptor blockers have an effect on progression from MCI to dementia.^21,22 Neither class is FDA-approved for treating MCI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and often of questionable clinical relevance.²³ Nonetheless, among ChEIs, donepezil is approved by the US Food and Drug Administration (FDA) for mild, moderate, and severe dementia and galantamine and rivastigmine are approved for mild and moderate dementia. There is no evidence that any one ChEI is more effective than any other,²⁴ and the choice of drugs is often guided by cost, adverse effects, and health plan formularies. Memantine, the only FDA-approved NMDA receptor blocker, is approved for moderate to severe dementia and can be used alone or in combination with a ChEI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and are often of questionable clinical relevance. If these drugs are used in an attempt to improve cognition in AD, guidelines recommend the following approach for initial therapy: Prescribe a ChEI for the mild stage, a ChEI plus memantine for the moderate stage, and memantine (with or without a ChEI) for the severe stage.²⁵ The recommendations also include monitoring every 6 months.

There is no consensus about when to discontinue medication. Various published recommendations call for continuing treatment until the patient has “lost all cognitive and functional abilities;”²² until the patient’s MMSE score falls below 10 and there is no indication that the drug is having a “worthwhile effect;”²¹ or until he or she has reached stage 7 on the Reisberg Functional Assessment Staging scale, indicating nonambulatory status with speech limited to one to 5 words a day.¹⁰

Behavioral function. A variety of drugs are used to treat behavioral symptoms in AD. While not FDA-approved for this use, the most widely prescribed agents are second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone). The main effect of these drugs is often nothing more than sedation, and one large multisite clinical trial concluded that the adverse effects offset the benefits for patients with AD.²⁶ Indeed, the FDA has issued an advisory on the use of second-generation antipsychotics in AD patients, stating that they are associated with an increased risk of death.²⁷ The recently updated Beers Criteria strongly recommend avoiding these drugs for treating behavioral disturbances in AD unless nonpharmacologic options have failed and the patient is a threat to self or others.²⁸

The FDA has issued an advisory on the use of second-generation antipsychotics in Alzheimer’s patients, stating that they are associated with an increased risk of death. Because of the black-box warning that antipsychotics increase the risk of death, some physicians have advocated obtaining informed consent prior to prescribing such medications.²⁹ At the very least, when family or guardians are involved, a conversation about risks vs benefits should take place and be documented in the medical record.

Other drug classes are also sometimes used in an attempt to improve behavioral function, including anti-seizure medications (valproic acid, carbamazepine), antidepressants (trazodone and selective serotonin reuptake inhibitors), and anxiolytics (benzodiazepines and buspirone). Other than their sedating effects, there is no strong evidence that these drugs are effective for treating dementia-related behavioral disorders. If used, caution is required due to potential adverse effects.

Nonpharmacologic management is “promising”

A recent systematic review of nonpharmacologic interventions for MCI evaluated exercise, training in compensatory strategies, and engagement in cognitively stimulating activities and found “promising but inconclusive” results. The researchers found that studies show mostly positive effects on cognition but have significant methodologic limitations.³⁰ Importantly, there is no evidence of delayed or reduced conversion to dementia.