Alzheimer's Disease

The global management of AD includes a number of steps (see Table 4). In most countries the family practitioner handles them all, in consultation with a variety of health professionals and other community resources throughout the course of AD. For instance, an atypical presentation or pattern of progression may suggest a diagnosis of dementia other than AD, and an expert diagnostic opinion may be needed. Depression or cognitive or behavioral symptoms unresponsive to standard pharmacotherapy may require a trial of another class of drug, with input from experienced clinicians.

Many patients in early stages of AD require treatment with an antidepressant, preferably of the selective serotonin reuptake inhibitor class, for six to twelve months. Most will want to try a cholinesterase inhibitor (CI) in an attempt to increase brain acetylcholine levels and improve symptoms. Randomized clinical trials and clinical experience have shown that in mild to moderately severe stages of AD (stages 3 to 6), therapeutic doses of CI cause an initial improvement, variable between individuals. After nine to twelve months the improvement above the starting point is followed by a slower decline in cognition Table 4 Global management of Alzheimer's disease SOURCE: Author and functional autonomy relative to patients not on CI, for periods lasting up to three years. It is likely but not yet fully established that CI delays the emergence of neuropsychiatric symptoms seen in stages 5 and 6. There has been some disappointment at the modest size of improvement, the relatively short duration of benefit, and the lack of predictability of who will improve. A more realistic expectation is a delay in progression of symptoms until drugs (currently in various phases of experimental testing) acting on the pathophysiology of AD are proven safe and effective, leading to a combination of symptomatic and stabilization therapy.

A number of possible treatments to delay progression of AD, based on data generated from large-scale epidemiological studies, human brain banks, and the transgenic animal models of AD (see Table 6), are available for evaluation. Largescale randomized studies are required to test these, some as long as five years, depending on the therapeutic target (for instance, delaying emergence of cognitive symptoms in healthy elderly persons, or conversion from mild cognitive impairment to diagnosable AD).

Table 5 Cholinesterase inhibitors in use for the symptomatic treatment of Alzheimer's disease SOURCE: Author