Alzheimer's disease (AD), the irreversible and progressive brain disease, is the most common cause of dementia in older Americans. People affected by Alzheimers lose their abilities to reason and think clearly, care for themselves and perform activities of daily life. Eventually, they are unable to recognize others and remember events and skills.

The signs of Alzheimer's typically show up when people are in their 60s, but they can occur earlier in life. Estimates show that over 5 million Americans may have Alzheimer's. Much research has gone into determining how to prevent it from occurring, and how to treat it once it strikes; but it is currently incurable. Available medications are variably disappointing in their ability to slow the loss of functioning.

Because Alzheimer's changes seem to develop over many years, much interest has been focused on risk factors that are present before old age.

Years before people show the behavioral features associated with AD, it is believed that changes are taking place in the brain. These changes are related to deposits of abnormal proteins that form amyloid plaques and tau tangles throughout the brain and prevent nerve cells from growing and functioning normally. Over time, the damage spreads to many parts of the brain, causing the loss of interconnections among cells and their ultimate death. The brain slowly loses its ability to function normally.

Stopping Alzheimer's Disease Before It Starts

Because Alzheimer's changes seem to develop over many years, much interest has been focused on risk factors that are present before old age. A recent study looked at factors that occur during midlife (45-64 years) that may impact the presence of the amyloid plaques later in life (67-88 years).

Since healthy blood vessel functioning is critical for nourishing brain tissues, the researchers were interested to see if factors that increased vascular disease might lead to the amyloid deposition that would eventually cause problems seen later in life.

First, the researchers identified some of the midlife health conditions that are vascular risk factors — hypertension, diabetes, smoking and high cholesterol — particularly when measured in midlife, have been associated with risk of dementia generally and AD specifically. Then, over the course of the study, they compared the types and numbers of midlife vascular risk factors to the amount of amyloid deposits that they could observe later on.

Over three hundred people took part in the study. Their mean age, at the start of the study, was 52 years. The study participants had an initial visit in 1987-1989. Over the years they had four more visits, as well as annual or semiannual telephone calls during the rest of the study.

At each point they were assessed for the presence of vascular risk factors, including a body mass index greater than 30 (obesity), smoking, hypertension, diabetes and total cholesterol. At the first visit, 20 percent of the participants had no risk factors, 38 percent had one risk factor and 42 percent had two or more risk factors for vascular disease.

Other factors, such as age, sex, race, genetic predisposition to Alzheimers and educational level, that might make a person predisposed to Alzheimer's were also included in the analysis. Cognitive function was evaluated at the second and fourth visits, and an in-depth neuropsychological evaluation was done at the fifth visit, between 2011-2013.

Twenty-some years after the start of the study, the amyloid deposits in participants' brains were analyzed using positron emission tomography, or PET scans.

As the number of midlife vascular risk factors increased, so did the presence of amyloid in the brain in late life.

The results revealed the importance of good midlife health in preparing for a healthy old age. Having a higher number of vascular risk factors in midlife increased your risk of elevated brain amyloid in later life. Thirty-one percent of participants with no risk factors in midlife had elevated brain amyloid later on, while 61 percent of those with at least two vascular risk factors in midlife did. As the number of midlife vascular risk factors increased, so did the presence of amyloid in the brain in late life.

Even when a participant had a genetic predisposition to Alzheimer disease, these findings did not change. Notably, there was no association between the number of vascular risk factors in late life and the deposition of amyloid.

Start Early

The message for those in their 40s and 50s is that researchers conclude that vascular risk factors in midlife, but not late life, are important for amyloid deposition. The findings support the idea that vascular disease plays a role in the development of Alzheimer's.

Since many midlife vascular risk factors can be modified with medications, diet and lifestyle changes, and other available interventions, the findings have important implications. If these findings are supported by additional research, efforts at prevention of dementia may need to start early on. A healthier midlife may set the stages for healthier aging for many people.

The study is published in JAMA, the Journal of the American Medical Association.