Stony Brook scientists new research on age-related brain decline

Alzheimer’s and other dementia-related conditions are some of the most cruel afflictions, as anyone can attest to who has had a loved one gradually losing the power of recognizing those closest to them, and beginning to live a life centered around confusion and anger. 

In the most extreme form, sudden violent outbursts add to the misery for all concerned.

But now, with groundbreaking research, scientists have discovered telltale signs of oncoming dementia as well as methods of preventing further cognitive decline. A study published by the National Academy of Sciences finds what it has termed “critical transition points” in the brain, and when interventions might be the most successful for patients.

Botond Antal, Ph.D., a postdoctoral associate in Biomedical Engineering at Stony Brook, said, “This represents a paradigm shift in how we think about brain aging prevention. Rather than waiting for cognitive symptoms, which may not appear until substantial damage has occurred, we can potentially identify people at risk through neuro-metabolic markers and intervene during this critical window.”

The breakthrough emerged from the work of an international team of scientists led by Lilianne R. Mujica-Parodi, Ph.D., of Stony Brook University (SBU).

According to SBU, the study, which looked at more than 19,000 individuals, found that “functional communication between brain regions (brain networks) begins to destabilize around age 44, with the degeneration of brain networks accelerating most rapidly at age 67 and plateauing by age 90. These transition points follow an S-shaped statistical curve with clear transition points, rather than either the late-life clinical onset or gradual linear decline previously assumed, suggesting there are specific windows when intervention could be most impactful.”

According to Ms. Mujica-Parodi, who is professor of Biomedical Engineering in the Laufer Center for Physical and Quantitative Biology and the Renaissance School of Medicine at SBU, this is a breakthrough that will spur more research, but already is on the road to help patients now. 

“We’ve identified a critical midlife window where the brain begins to experience declining access to energy but before irreversible damage occurs, essentially the ‘bend’ before the ‘break.’ During midlife, neurons are metabolically stressed due to insufficient fuel. They’re struggling, but they’re still viable.”

Researchers didn’t just map the trajectories of aging brains but, as the university reported, identified its primary driver: neuronal insulin resistance.   

“Understanding exactly when and how brain aging accelerates gives us strategic time points for intervention,” Ms. Mujica-Parodi said. “Therefore, providing an alternative fuel during this critical window can help restore function. However, by later ages, neurons’ prolonged starvation may have triggered a cascade of other physiological effects that make intervention less effective.”

According to the university, “By comparing metabolic, vascular, and inflammatory biomarkers, they found that metabolic changes consistently preceded vascular and inflammatory ones. Gene expression analyses further implicated the insulin-dependent glucose transporter GLUT4 and the lipid transport protein APOE (a known Alzheimer’s risk factor) in these aging patterns.”

The researchers also concluded that “an alternative brain fuel that neurons can metabolize without insulin — might be beneficial.” 

In a study of 101 participants at different stages of aging, researchers compared administration of individually weight-dosed and calorically matched glucose and ketones, which are acids that the body makes when breaking down fat for energy.   

The team found effects that were “striking,” adding that “unlike glucose, ketones effectively stabilized deteriorating brain networks … Ketones showed moderate benefits in young adults (20-39 years), showed maximum benefits during the midlife ‘metabolic stress’ period (40-59 years) after which networks begin destabilizing, but had diminished impact in older adults (60-79 years) once the network destabilization hit maximum acceleration and the domination of compounding vascular effects.”

The report said that “these findings could revolutionize approaches to preventing age-related cognitive decline and neuro-degenerative diseases like Alzheimer’s.”

Populations across the world are aging rapidly — according to some research, dementia cases could triple in the next 25 years to triple by 2050 — but the new breakthrough research could protect individuals and families from much misery and heartbreak.