Losing it... The challenge of diagnosing and managing cognitive impairment in older patients

With the aging of the U.S. population, more Americans are developing dementing illnesses such as Alzheimer's disease.¹ No treatments for these conditions are truly satisfactory, and many cause bothersome or dangerous side effects.

Addressing this problem can be one od the most difficult challenges in primary care; behavioral and community supports provide a helpful but under-utilized approach.

Getting the diagnosis right

Many people over age 60 have occasional minor memory lapses; it's critical to distinguish these normal changes from the onset of a dementing illness, and - if one is present - to gauge the severity of cognitive impairment.

No single test establishes the diagnosis of dementia. The Mini-Cog test² can rapidly screen for gross abnormalities of cognition and trigger further evaluation if needed. The test is quick and easy to administer.

Performing well on this test does not prove that the patient has normal cognition; more testing may be needed if symptoms persist.

The Mini-Mental State Exam (MMSE) can also be easily administered in the office.³ It evaluates cognition in five areas: orientation; immediate recall; attention and calculation; delayed recall; and language. A full description of the MMSE is provided in the accompanying evidence document. Test scores must be interpreted in the context of the patient's language, level of education, and developmental disability.⁴

Is there a treatable cause?

If no reversible cause is found...

... then the patient is probably suffering from an age-related cause of cognitive impairment. The most common diagnosis is Alzheimer's disease, but other conditions should be considered as well.

Causes of dementia in people over age 70:

• Alzheimer's disease, 70%
• Vascular dementia, 17%
• Other dementia, 13%

 Begin with non-drug approaches

It is tempting to write a prescription as the first approach to managing cognitive decline and the behavioral problems which may accompany it, but the drugs used for these conditions have many limitations. Starting with behavioral and environmental interventions can be effective, safer, and more affordable.

Some non-drug approaches can make it easier for patients and caregivers to cope with reduced memory,^{5, 6} although few have been clearly shown to help with cognitive decline. The best-studied include cognitive stimulation, spaced-retrieval technique, procedural motor memory training, and dual cognitive support^{5, 7-10} (see evidence document).

Drug treatment for cognitive impairment

The prescriber, patient, and caregivers must keep in mind that none of the available treatments work really well, and that all can cause side effects. The products currently on the market have shown statistical superiority over placebo, but in many studies this "advantage" may have been just a few points of change on a psychometric scale rather than a clinically noticeable improvement.^11-14

• All currently available drugs for cognitive impairment work about as well as each other.¹¹
• The cholinesterase inhibitors (donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon)), frequently produce anorexia, nausea, vomiting and/or diarrhea. They can also cause adverse cardiac outcomes.
• Memantine is generally well tolerated but can cause hypertension, dizziness, and adverse CNS and gastrointestinal effects.
• All these drugs are costly, which can be a problem for many patients.

Dealing with the behavioral problems of dementia

Cognitive impairment is often accompanied by behavioral disorders that range from odd to annoying to life-threatening, and may precipitate institutional placement.15-18 The drugs used to treat this component of dementia generally act by sedating the patient, which can further worsen cognitive function. Benzodiazepines can sometimes precipitate a paradoxical reaction that makes the patient more, rather than less agitated.

Antipsychotic drugs such as risperidone (Risperdal), olanzapine (Zyprexa), haloperidol, and quetiapine (Seroquel) have been widely used to manage behavioral problems in older patients with dementia, but there are problems with this approach.

•  No antipsychotic agent has been FDA-approved for behavioral symptoms in the elderly.¹⁹
• Both conventional and atypical antipsychotics can increase the risk of death, causing the FDA to place a black-box warning on each.¹⁹
• There is little evidence that any one antipsychotic works significantly better than any other or placebo.
• Most of the newer ("atypical") antipsychotics substantially raise the risk of weight gain and diabetes.

Before prescribing an antipsychotic drug for an older patient with cognitive impairment

• Assess and treat any underlying medical conditions that may be contributing to the problem (e.g., pain, delirium, depression).
• Review any medications that may be implicated (e.g., anticholinergics, psychotropics).
• Identify one or more target behaviors that warrant drug treatment..
• Consider whether these behaviors pose a risk to the patient or others, or are merely a nuisance.
• Determine the behavioral goal being sought for each target problem, and how it will be assessed.
• Implement all practical environmental and behavioral interventions.
• Start with the lowest possible dose if a drug must be used.
• Monitor carefully for expected side effects, including metabolic (increase in serum glucose, weight gain), cardiac (Q-T prolongation on ECG, new onset cardiac symptoms), and behavioral (excessive sedation, worsening of cognitive impairment).
• Reassess the need for medication regularly.
• Reduce dose or stop treatment if target behaviors improve or if unacceptable side effects occur.

Whether or not medications are used, community resources are an essential part of managing patients with memory and behavioral problems

Area Agencies on Aging (AAA) and other community services can provide useful help to older patients and their families in coping with cognitive impairment. Sometimes this can enable a person to remain at home and avoid or delay the need for institutionalization. See http://www.n4a.org/about-n4a/?fa=aaa-title-VI for national information. Information specific to Pennsylvania is at http://www.aging.state.pa.us/aging/cwp/view.asp?a=275&Q=177124

References:

1. National Institute on Aging, National Institutes of Health, US Department of Health and Human Services. Alzheimer's Disease: Unraveling the Mystery. Available at http://www.nia.nih.gov/NR/rdonlyres/0FA2EE06-0074-4C45-BAA3-34D56170EB8B/0/Unraveling_final.pdf.2008. 2. Borson S, Scanlan J, Brush M, Vitaliano P, Dokmak A. The mini-cog: a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly. International Journal of Geriatric Psychiatry. Nov 2000;15(11):1021-1027. 3. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A Practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research. 1975;12(3):189-198. 4. National Institute of Clinical Excellence. Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease (amended). Technology Appraisal. Available at www.nice.org/uk/TA111. 2007. 5. National Institute for Clinical Excellence. Dementia: the NICE-SCIE guideline on supporting people with dementia and their carers in health and social care. National Clinical Practice Guideline Number 42 2007; 1-191: London, The British Psychological Society & The Royal College of Psychiatrists; 2007. 6. Clare L, Woods RT. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia (Cochrane Review). Cochrane Database of Systematic Reviews. Issue 4 Art. No.:CD003260 ed.2003: pp.DOI: 10.1002/14651858.CD003260. 2003. 7. Knapp M, Thorgrimsen L, Patel A, et al. Cognitive stimulation therapy for people with dementia: cost-effectiveness analysis. Br J Psychiatry. Jun 2006;188:574-580. 8. Onder G, Zanetti O, Giacobini E, et al. Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: randomised controlled trial. Br J Psychiatry. Nov 2005;187:450-455. 9. Spector A, Thorgrimsen L, Woods B, et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Br J Psychiatry. Sept 2003;183:248-254. 10. Acevedo A, Loewenstein DA. Nonpharmacological cognitive interventions in aging and dementia. Journal of Geriatria Psychiatry and Neurology. Dec 2007;20(4):239-249. 11. Birks J. Cholinesterase inhibitors for Alzheimer's disease (Cochrane Review). Cochrane Database of Systematic Reviews. Issue 1 Art. No.:CD005593 ed.2006:pp DOI: 10.1002/14651858.CD005593. 2006. 12. Farlow MR, Graham SM, Alvan G. Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. Drug Safety. 2008:31(7):577-585. 13. Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148:379-397. 14. McShane R, Sastre A, Minakaran N. Memantine for dementia. (Cochrane Review). Cochrane Database of Systematic Reviews. Issue 2. Art. No.:CD003154 ed.2006.pp. DOI: 10.1002/14651858.CD003154.pub5. 2006. 15. Lawlor BA. Behavioral and psychological symptoms in dementia: the role of atypical antipsychotics. The Journal of Clinical Psychiatry. 2004;65 Suppl 11:5-10. 16. Byrne GJ. Pharmacological treatment of behavioural problems in dementia. Australian Prescriber. 2005;28:67-70. 17. Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nature Reviews Neuroscience. June 2006;7(6):492-500. 18. Ballard C, Waite J, Birks J. Atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database of Systematic Reviews (Online). 2006(1):CD003476. 19. US Food and Drug Administration. Information for Healthcare Professionals: Antipsychotics. Available at http://www.fda.gov/cder/drug/InfoSheets/HCP/antipsychotics_conventional.htm. 2008. 20. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. The New England Journal of Medicine. 2009;360(3):225-235.
   

Additional references documenting these recommendations are provided in the evidence document accompanying this material.

This material was produced by Leslie Jackowski, B.Sc.(Hon).,M.B.B.S., Research Fellow, Harvard University; Niteesh K. Choudhry, M.D., Ph.D., Assistant Professor of Medicine, Harvard Medical School; Michael A. Fischer, M.D, M.S., Assistant Professor of Medicine, Harvard Medical School; and William H. Shrank, M.D., M.S.H.S., Assistant Professor of Medicine, Harvard Medical School. Series editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs Avorn, Choudhry, Fischer, and Shrank are all physicians at the Brigham and Women's Hospital in Boston.

The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania, the Washington D.C. Department of Health, and the Department of Public Health of the Commonwealth of Massachusetts. This material is provided by the nonprofit Alosa Foundation, which is not affiliated in any way with any pharmaceutical company.

These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient's clinical condition.