Dr. Small described brain aging as a continuum. Some people may have mild age-associated memory impairment. This may progress to mild cognitive impairment. The end result of this process is dementia.

The transition between these phases is not precise, however. In fact, the brain undergoes very gradual changes. Normal people with some age-related memory loss may exhibit some plaques and tangles. There is a characteristic buildup of lesions over time. Autopsy studies of persons with dementia will reveal a high concentration of plaques and tangles.

Technological advances in imaging can provide an advantage in early detection of age-related memory loss. For example, modern positron emission tomography (PET) scans utilizing a radioactively labeled glucose analogue can show the metabolic activity of cells.

Dr. Small and colleagues performed PET imaging studies in patients with normal memory performance. Some of the patients had the epsilon 4 allele of the apolipoprotein E gene (APOE-4), the primary known genetic risk factor for Alzheimer’s disease. Patients with a single APOE-4 allele had lower lateral temporal, inferior parietal, and posterior cingulate metabolism. This predicted cognitive decline at 2 years of follow-up.

Investigators have also used APOE-4 in conjunction with magnetic resonance imaging to identify subtle brain abnormalities. Investigators gave study subjects a memory test. Subjects with the APOE-4 allele had a greater magnitude of brain activation during the test. It is possible that different patterns of brain activation could predict later declines in memory.

Early intervention may prevent or slow down the progression of memory loss. Dr. Small said protecting intact neurons would be easier than trying to repair damage already done.

One strategy is drug treatment. Cholinesterase inhibitor trial data suggest earlier treatment improves outcome. In one study, patients received donepezil or placebo during a double-blind period. Then, after a 3-week washout, most subjects received donepezil 10 mg/day. As the chart shows, there is an apparent benefit for people who had received high-dose donepezil in the double-blind phase.

Researchers are studying early treatment in ongoing studies of patients with only mild impairment. Using PET scanning as a surrogate marker to track progression, they hope to see whether early drug interventions affect brain metabolism in key memory regions. He said the field is moving forward with many compounds to see if these treatments will delay onset of dementia.

Dr. Small said a number of “brain fitness strategies” may be helpful in preventing brain aging. For example, some drugs for physical illnesses may improve brain health. These include statins, antihypertensives, and perhaps non-steroidal anti-inflammatory drugs.

Physical activity may be another way to improve brain fitness. A large study has shown that leisure activity involving mental effort lowers dementia risk among seniors. In addition, studies of volunteers show that aerobic conditioning programs improve mental function.

Lifestyle choices may be important. For example, quitting smoking may reduce risk for dementia later in life, while some epidemiological data show that drinking alcohol in moderation is associated with lower risk for dementia.

The effect of diet on the brain is very difficult to assess. However, moderating caloric intake can lower risk of obesity and associated diseases such as diabetes and hypertension, which can lead to strokes. Some data suggest antioxidants may lower risk of cognitive decline. In addition, diets rich in omega-3 fatty acids are associated with better brain performance scores.

Finally, mental activity is very important. Dementia risk is lower in college graduates. Mentally challenging leisure activity may reduce Alzheimer’s disease risk. In addition, specific memory training techniques may effectively improve memory scores in older adults.

Ball et al. showed this in a compelling study published in 2002 in the Journal of the American Medical Association. The study included more than 2,800 volunteers aged 65 to 94 years randomized to group training in verbal memory, reasoning, processing speed or no intervention. Each intervention improved the targeted cognitive symptom, and booster training enhanced the benefit; participants maintained improvements at 2-year follow-up.