Nonesterified fatty acids, cognitive decline, and dementia

Dementia is rapidly growing as sources of morbidity and mortality as the US population ages, but its pathophysiology remains poorly understood. As a result, no disease-modifying treatments currently exist. We review the evidence that nonesterified fatty acids may play a key role in this condition.

Nonesterified fatty acids appear to influence several pathways leading to dementia. In addition to their vascular effects, these moieties cross the blood-brain barrier, where they are toxic to several cell types. They may also influence insulin metabolism in the brain directly and indirectly, and some drugs that lower circulating levels appear to slow cognitive decline and brain atrophy in diabetes.

Nonesterified fatty acids may contribute to dementia, much as they do to diabetes and cardiovascular disease. Several therapeutic agents lower circulating levels of nonesterified fatty acids and should be tested for their potential preventive effects on cognitive decline in healthy populations before irreversible neuronal attrition occurs.