Scientists discover first physiological sign that indicates Alzheimer's

Scientists have identified the first physiological sign to indicate Alzheimer's disease - a decrease in blood flow in the brain - using a powerful tool to better understand the progression the debilitating disease.

Led by Alan Evans, a professor at the Montreal Neurological Institute (MNI) in Canada, the researchers analysed more than 7,700 brain images from 1,171 people in various stages of Alzheimer's progression using a variety of techniques including magnetic resonance imaging (MRI) and positron emission tomography (PET).

Blood and cerebrospinal fluid were also analysed, as well as the subjects' level of cognition.

The researchers found that, contrary to previous understanding, the first physiological sign of Alzheimer's disease is a decrease in blood flow in the brain. An increase in amyloid protein was considered to be the first detectable sign of Alzheimer's.

While amyloid certainly plays a role, this study finds that changes in blood flow are the earliest known warning sign of Alzheimer's. The study also found that changes in cognition begin earlier in the progression than previously believed.

Late-onset Alzheimer's disease (LOAD) is an incredibly complex disease but an



equally important one to understand. It is not caused by any one neurological mechanism but is a result of several associated mechanisms in the brain.

LOAD is the most common cause of human dementia and an understanding of the interactions between its various mechanisms is important to develop treatments.

Previous research on the many mechanisms that make up LOAD has been limited in scope and did not provide a complete picture of this complex disease. This study factored in the pattern of amyloid concentration, glucose metabolism, cerebral blood flow, functional activity and brain atrophy in 78 regions of the brain, covering all grey matter.

"The lack of an integrative understanding of LOAD pathology, its multifactorial mechanisms, is a crucial obstacle for the development of effective, disease-modifying therapeutic agents," said Yasser Iturria Medina, a post-doctoral fellow at the MNI.

The trajectory of each biological factor was recorded using data from each patient taken over a 30-year period. This process was then repeated 500 times to improve robustness of estimations and stability of the results.

The study was published in the journal Nature Communications.