The evolutionary origins of dementia.

Evidence has grown that the core pathology of age-related dementias, including Alzheimer's disease, is microvascular-small, symptomless bleeds from cerebral capillaries, accelerated by the hypertension of age. Each such bleed, this evidence suggests, damages a patch of brain, causing the death of neurons. This review asks how this vulnerability of the brain emerged from evolution, to cause age-related dementia? And has the vulnerability spurred the evolution of mitigating mechanisms? It is argued that seven features of human evolution contribute to the cause of dementia: the dependence of our tissues, especially the brain, on oxygen; the toxicity of the molecule (heme) that binds to oxygen to enable its transport; the pulsatility of the heart; the danger of glutamate as an excitatory neurotransmitter; the irreparability of elastin; the low level of adult neurogenesis in humans; and the breakdown, in late life, of the blood-brain barrier. Also discussed are mechanisms that have evolved to counter these threats to the brain, including the generation of a reserve of brain tissue. We argue that the vulnerabilities of the brain to damage that accumulates throughout life, and leads to dementia in the aged, were established early in the evolution of vertebrates. Several can be understood as unavoidable yet damaging outcomes of highly advantageous steps in evolution. Human cognition fails when and because, with age, the damage that results from these vulnerabilities overwhelms the evolved protections and exhausts any reserve of brain tissue. Implications of these vulnerabilities for the delay and management of dementia are discussed.