Alzheimer disease: Time to improve its diagnosis and treatment

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ABSTRACTBasic research is bringing a much-needed infusion of optimism and urgency to the clinical diagnosis and treatment of Alzheimer disease. Some of its risk factors may be modifiable, and although current drugs offer only modest benefit, true disease-modifying drugs are on the horizon. This review is aimed at primary care physicians, who are the first clinicians to see patients with Alzheimer disease and are responsible for their ongoing care throughout the course of their dementia.


  • Interpret screening tests carefully in patients who have very low or very high education levels, who are not tested in their native language, or who have deficits that might limit their performance.
  • Patients with Alzheimer disease function best in a safe, calm, and predictable environment. Their caregivers require ongoing support and education to develop realistic expectations throughout the course of the illness.
  • It is important that families be made aware that treatments for Alzheimer disease, such as cholinesterase inhibitors, attenuate decline over time rather than improve cognitive and behavioral symptoms.
  • Evidence is growing that nutritional factors (eg, dietary restriction, antioxidant intake, and the Mediterranean diet) and lifestyle factors (eg, social and mental activity and exercise) can delay the onset of Alzheimer disease.



The number of patients with Alzheimer disease, the most common cause of disability in the elderly, is about to rise dramatically. More than 5 million people in the United States are affected, and by 2050 this figure may rise to between 11 and 16 million.1 The prevalence doubles every 5 years from ages 65 to 85, so that Alzheimer disease affects 30% to 50% of all people at age 85.1,2

Primary care physicians bear the brunt of diagnosing and treating all these patients,3 requiring that they have the training to meet this critical public health problem.

But diagnosing this disease is not easy. In the early stages, it can be difficult to distinguish between the decline in certain cognitive functions due to normal aging (eg, name recall) and the mild cognitive impairment that often precedes Alzheimer disease.

Once a patient is diagnosed with Alzheimer disease, there needs to be a realistic discussion with the patient and family about what treatment with different drugs can—and cannot—accomplish.


While much has been accomplished in Alzheimer disease research in the last 20 years, a great deal remains to be done to improve its diagnosis and treatment. There is increasing evidence that early diagnosis of Alzheimer disease will be key to maximizing treatment benefits. But too often, patients are diagnosed in later stages of the disease, when disabling symptoms and neuropathologic changes have become well established.

Mild cognitive impairment: A predementia phase

The pathologic changes of Alzheimer disease typically begin many years before its clinical signs are apparent. Most patients pass through a predementia phase called mild cognitive impairment, with early memory loss but with relatively well-preserved activities of daily living.

From 6% to 25% of patients with mild cognitive impairment progress to dementia annually, a rate far higher than the incidence rate in the general population of 0.3% to 3.9% per year, depending on age.4,5 Therefore, patients with mild cognitive impairment are a good population in which to test interventions to prevent dementia.6,7

The concept of mild cognitive impairment is controversial because it is a transitional stage between normal aging and dementia rather than a distinct pathologic entity.8 Moreover, in some large community-based studies,9,10 a sizeable number of people with mild cognitive impairment reverted to normal cognitive function over 5 years, suggesting that mild cognitive impairment may be unstable over time.

Are other factors causing the dementia?

The Diagnostic and Statistical Manual IV-Text Revision11 defines dementia as memory loss and at least one other area of cognitive impairment, not due to delirium, that interferes with social and occupational functioning. Alzheimer disease is the most common cause of dementia in the United States.1

Still, Alzheimer disease does not typically exist in isolation. For example, while Alzheimer disease was the predominant cause of dementia in a recent postmortem series, 38% of dementia cases featured Alzheimer disease with lacunar infarction.12 Accordingly, clinicians must consider factors other than Alzheimer disease that could contribute to (or even fully account for) the complaints or observed deficits.

Is it Alzheimer disease or normal aging?

Although cognitive impairment and changes in behavior are common in the elderly, they are not a normal part of aging. Like other chronic disorders associated with aging, Alzheimer disease can be diagnosed and treated. Cognitive impairment may come to light when the patient or a family member reports a problem or the clinician asks about problems or observes signs of impairment in the office. The cognitive difficulties should be taken seriously, and their impact on daily functioning should be evaluated.

Certain cognitive functions such as mental flexibility and speed of processing decline in normal aging,13 and many older people report cognitive symptoms. Therefore, it is important to differentiate mild age-associated cognitive changes from the beginning of a cognitive disorder such as Alzheimer disease. This can be difficult because the cognitive complaints of normal aging overlap with the symptoms of early Alzheimer disease, and there are no clear rules for distinguishing the two.13

Clues that a more serious problem exists may come from details such as a history of decline in cognitive abilities, involvement of more than one domain, and the extent to which the problem disrupts daily functioning. 13 When evaluating the nature and severity of a cognitive disorder, one must take into account the patient’s level of education, premorbid intellectual and occupational functioning, and concurrent medical and psychiatric conditions. Clinicians must also consider the impact that medications, possible substance abuse, and language and culture of origin have on cognition.

The most common cognitive complaints in the elderly tend to be related to working memory (eg, recalling the name of a recent acquaintance or a telephone number that was just looked up).14 Other common complaints center on the speed of mental processing (eg, thinking quickly), memory (eg, recalling the name of an old acquaintance, or remembering where objects were placed or why one entered a room), executive function (eg, multitasking or planning a series of events), attention, and concentration.14

People with age-related cognitive changes can learn new information and recall previously learned information, although they may do so less rapidly and less efficiently. Furthermore, age-related cognitive change is not substantially progressive and does not significantly impair daily functioning.14 Nevertheless, complaints of cognitive changes should be monitored, since several studies showed that elderly people with cognitive complaints have an increased risk of developing dementia.15,16


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