Southwestern Internal Medicine Conference
The Primary Care of Alzheimer Disease

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ABSTRACT

Alzheimer disease is the most common cause of progressive irreversible intellectual loss in aging humans. The number of individuals and families affected by this disorder will continue to grow as society ages worldwide. Our understanding of the biology, underlying pathophysiology, and diagnosis of Alzheimer disease has greatly expanded over the past few years and much has been published in these areas. This review focuses on the primary care of this disorder and addresses the “now what” question. Topics examined include limiting excess disability, responding to commonly raised questions of family members, pharmacologic and nonpharmacologic therapeutic options, long-term planning, and caregiver issues.

Section snippets

Limiting Excess Disability by Optimal Management of Comorbid Conditions

The value of a complete medical evaluation of a patient with AD is to ascertain the overall medical status of the individual. This helps the family understand the overall health status of the individual and to optimally manage other problems that may have an impact on the individual’s functional state. Reversible conditions should be treated.

Polypharmacy and Adverse Drug Reactions

Patients with AD are particularly vulnerable to the adverse effects of anticholinergic drugs. Loss of the cholinergic synapses and neurons that support memory function is one of the cardinal features of AD. A prudent therapeutic strategy is to eliminate all nonessential medications and in particular to shun anticholinergic agents that may further impair cholinergic and cognitive function. Furthermore, the use of unproven treatment guidelines in older patients with comorbidity may lead to

Sensory Impairment

Attention to sensory losses is important. If the patient has not had a visual assessment, this should be completed and refractive errors corrected. Hearing loss is common and what is not heard cannot be remembered. However, hearing aids are generally not recommended. In addition to their high cost, they often are lost; patients have difficulty applying and adjusting them; and they forget to use them. Appropriate communication for hearing-impaired individuals (speaking face-face) is more useful

Cardiovascular Disease and Alzheimer Risk

Hypertension and other cardiovascular risk factors are common in the aged with and without AD.25., 26. There is some evidence that cerebrovascular disease can aggravate dementia in patients with AD and also be a direct cause of dementia. It makes inherent sense to avoid additional cerebral injury in the brain of an AD patient who is already being ravaged by neuronal loss and injury. The former may be preventable even though the latter currently is not. The diagnosis of Mixed Dementia (AD plus

Depression

Patients should be evaluated for depression for two reasons. It is a common problem that can clinically present with cognitive symptoms such as marked inability to concentrate (dementia of depression; pseudodementia) and should be identified and treated appropriately. Furthermore, patients with dementia can develop depression and, to the extent the depression can be treated, the patient’s functional state can improve. Patients with dementia may not be able to offer a history of depression, but

Case Report

MJ is an 81-year-old man with AD. The patient’s wife reported that he had over the preceding week started complaining of anxiety over their lack of money and that they were destitute. He would not accept any assurances by his wife and family that there were no financial problems. He stated he understood what his family was saying but assured his physician that he knew he had no money and that his family was just wrong. He had difficulty sleeping and began to lose weight because he declined

Health Maintenance

The appropriateness of ongoing health maintenance measures should be considered. Routine vaccinations should generally be continued and other screening measures should be considered in the context of comorbidity and the clinical state of the patient.

Disease Progression and Survival

Families frequently inquire about the life expectancy of their relative diagnosed with AD. Larson et al45 found the median survival from initial AD diagnosis of 521 patients enrolled in a managed care organization was 4.2 years for men and 5.7 years for woman, equal to about half that predicted using U.S. Census life tables. Predictors of mortality included an MMSE score of 17 or less and a Blessed Dementia Rating Scale score of 5 or greater,46 presence of frontal lobe release signs, presence of

Family Risk

Children of people with AD are often concerned about their risk of developing the disease. Increasing age, female sex, family history, and presence of one or two copies of the apolipoprotein E €4 allele are risk factors for AD.49

Autosomal dominant AD beginning before 60 years of age accounts for less than 1% of cases of AD worldwide. Fifty percent of these cases are thought to involve mutations in the presenilin 1,2 or the amyloid precursor protein (APP) gene.50 The lifetime risk of AD at age 65

Outcome Scales Used to Assess Interventions in Alzheimer Disease

A variety of scales are used to evaluate the efficacy of pharmacologic interventions for AD. They can be grouped into four major domains: cognition, behavior, function, and global assessment. Some understanding is necessary to interpret the significance of findings in intervention trials and to appreciate the magnitude of effect size. Many different assessment tools exist, but the following is a summary of some commonly used ones. Examples of the actual tools are readily available in related

ADAS-cog

Probably the most common tool to assess cognition in patients with mild to moderate disease is the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog).58 This tool is used to measure selective elements of cognitive function, specifically memory, orientation, language, reasoning, and practices. The scoring ranges from 0 to 70, with higher scores indicating increased magnitude of cognitive impairment. There are 11 individual tests. Spoken language ability (0–5), comprehension of

Global Assessment

The Clinician’s Interview-Based Impression of Change scale (CIBIC-plus)65 provides a global rating of patient function in four areas: general, cognitive, behavioral, and activities of daily living (ADL). Measurements are derived through independent, comprehensive interviews of the patient and caregiver by a trained clinician who is blinded to all other patient assessments and outcomes. Patients are scored on global severity at baseline and subsequent assessments on a scale of 1 to 7 are

Physical Function

Overall physical function is assessed by evaluating ADLs. A variety of tools have been used. Some include:

The ADCS (AD Cooperative Study-Activities of Daily Living inventory) ADL19 is a 19-item inventory of items appropriate for evaluating later stages of dementia. The tool can be administered as an interview of patient’s caregivers. Scores range from 0 to 54. Higher scores reflect higher levels of functioning.66

The Progressive Deterioration Scale (PDS)67 is a disease-specific measure of

Behavioral Assessments

The Neuropsychiatric Inventory (NPI)69 is a 12-item, caregiver administered instrument used to evaluate behavioral and neuropsychiatric symptoms, including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy, disinhibition, irritability, aberrant motor behavior, night-time behavior, and appetite/eating disorder. Frequency is rated from 1 (occasional, less than once a week) to 4 (very frequent) and severity from 1 (mild) to 3 (severe). The

Pharmacologic Agents for the Treatment of Agitation and Other Behavioral Symptoms Associated with Dementia

Agitation is a common problem associated with demented patients, occurring in as many as 70% of patients.109 Agitation can be defined as “inappropriate verbal, vocal, or motor activity that is not explained by needs or confusion per se.”110 Agitation may be manifest by wandering, crying out, assault, hostility, suspiciousness, or aggression. A number of agents are used in clinical practice to treat agitation, including benzodiazepines, neuroleptics, antidepressants, beta-blocking agents,

Future Directions

Over the past couple of decades there has been increasing understanding of the biology of AD. Recent investigations have revolved around attempts to develop a vaccine to reduce or eliminate the accumulation of amyloid plaques (composed of amyloid-β-peptide [Aβ], a 40–42-amino-acid fragment of the β-amyloid precursor protein [APP]). Amyloid plaques are thought by many to be the cause of cognitive decline in AD. In 1995, Games et al136 reported that production of transgenic mice that express high

Conclusion

Unfortunately Alzheimer disease is an all too common disease affecting millions of people worldwide. Comprehensive medical care is essential to maximize function and limit disability. Treatable and reversible comorbid problems should be identified and optimally managed. Family and caregiver education and support are a critical component of care. Currently available medications have a small clinical effect but should be considered. They may improve global and cognitive symptoms and slow progress

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    This work was supported by the Margaret and Trammell Crow Fund for Alzheimer and Geriatrics Research.

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