Genetic Mapping in Combination with Brain Imaging May Help Diagnose Early Dementia

Alzheimer's disease, which is the most common form of dementia, is an irreversible, progressive disorder that causes the brain cells (neurons) to degenerate. This results in loss of cognitive functions – primarily memory, language, and abstract thinking. Eventually, all mental functioning may be lost.

Currently, there is no cure for Alzheimer’s disease, but there are treatments that may help prevent some symptoms from becoming worse. This makes early detection crucial. However, at present, since the defining neuronal hallmarks can not be detected in the living brain, the diagnosis is based mainly on behavioural symptoms and by excluding other possible causes. This means that by the time the patient starts treatment, he or she already suffers from irreversible and disabling brain damage.

While scientists have not yet identified any single reason why cells fail, they have identified certain risk factors that increase the likelihood of developing Alzheimer’s. In addition to increased age, one major risk factor is a specific form of the gene that codes for apolipoprotein E (APOE å4).

By using magnetic resonance imaging (MRI), our research group found that healthy, non-demented carriers of APOE å4 have structural as well as functional brain alterations that are similar to what is commonly seen in Alzheimer’s disease patients. Given that APOE å4 increases the risk for Alzheimer’s, and the fact that the Alzheimer’s disease process likely begins years, sometimes even decades, before any cognitive symptoms occur, these findings may represent preclinical markers of impending dementia.

One main finding was that the at-risk individuals had reduced neuronal activation in posterior parts of the brain (the parietal cortex), and that the degree of parietal activation predicted memory decline two to three years later. In other words, the lower the activation, the greater memory decline. Indeed, memory decline is one of the first and most prominent behavioural signs of Alzheimer’s. This finding is of particular high interest, given that APOE å4 is not consistent markers for Alzheimer’s disease. Indeed, many carriers of APOE å4 remain healthy.

Thus, brain imaging may help us to discriminate between at-risk individuals who will or will not ultimately develop dementia. This is an important step towards better diagnostic methods. If the method is developed, people at increased risk may be identified and start preventive treatment before severe brain damage develops.

Reference:

Thesis: Memory, genes, and brain imaging - relating the APOE gene to brain function and structure; Lind, Johanna