A radical new approach may overturn the prevailing medical wisdom that Alzheimer’s disease has its origins in the brain, according to a new review of the evidence.
The alternative explanation argues that aged-related dementia has an earlier origin in the heart and vascular system, not the brain.
If the rival theory is correct, it will require a major rethink of drug therapies, and the level and direction of research investments, currently aimed at preventing and treating a disease that will soon engulf 100 million globally.
The established medical view is that Alzheimer’s is primarily a degenerative disease of the brain caused by beta-amyloid senile plaques and neurofibrillary tangles—that interfere with neural pathways and signalling.
Whether these plaques and tangles are the primary cause for the onset of Alzheimer’s is still uncertain.
“Aged-related dementia is the result of undetected bleeding into the brain caused by the lifelong destructive effects of the heart’s pulse on tiny blood vessels in the brain,” says Jonathan Stone, Professor of Neurobiology at the University of Sydney.
Together with colleagues from the University of Sydney and the Victor Chang Cardiac Research Institute, Stone led a recently published comprehensive review assessing the vascular explanation for age-dementia in the Journal of Alzheimer’s Disease.
“If we live to old age, the heart destroys us. That’s the conclusion more scientists are beginning to take seriously,” he says.
“We propose that dementia is primarily vascular, caused by the destructive effect of the pulse on the cerebral blood vessels, with the loss of neurons and the pathology that Alois Alzheimer described over a century ago occurring secondarily to vascular breakdown.
“We argue, further, that dementia is age-related because the pulse becomes more intense and destructive with age.”
Over the course of a lifetime, the aorta gradually hardens as the elastin in the wall of the aorta starts to fail. As an analogy, a 20-year-old’s artery is like a flexible balloon, while an 80-year-old’s artery is more like a stiff, hard garden hose.
“As this hardening happens, the aorta causes higher peaks and troughs resulting in higher blood pressure as a person ages,” says Stone. “With blood spurting into them with increasing intensity, the brain’s blood vessels become damaged.”
A major contribution to understanding has come from the insights of research cardiologists, in particular Dr Michael O’Rourke of the Victor Chang Institute, who has drawn a correlation between age-related stiffening of the aorta and an increase in the intensity of the pulse. This may be the factor which links age to dementia.
Researchers from the University of Sydney, the Brain and Mind Research Institute, the George Institute for Global Health, and the University of Cambridge are following the vascular explanation to lead a world-first effort to prevent dementia.
Using a suite of new electronic and web-based interventions, they will soon commence a massive trial of low cost, high impact interventions targeting dementia risk factors in 40,000 people aged 50 to 80 years.