Dementia in older population linked to concurrent neuropathologies

CHICAGO — Alzheimer’s disease-related dementia among older adults is linked to a combination of neurodegenerative and vascular pathologies, according to a presenter at the 2022 American Neurological Association annual meeting.

“There are multiple biological pathways to Alzheimer’s dementia,” Julie A. Schneider, MD, MS, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences at Rush University Medical Center, said in her presentation. “We think of Alzheimer’s disease as being amyloid and tau, but we’ll see that very rarely do we just see amyloid and tau.”

Very often, Schneider said, AD-related dementia is linked with three other biologic pathways: vascular pathology, Lewy bodies, and TDP-43, also known as Limbic-predominant age-related TDP-43 encephalopathy, an abnormal protein linked to memory loss.

Amnestic dementia in aging populations, she added, is a heterogeneous mix of neurodegenerative and vascular pathologies, which interact. When these pathologies converge, there is a lower threshold for dementia.

Common pathways underlying genetic and environmental factors, which include traumatic brain injury, also contribute to an individual’s susceptibility and resilience to these pathologies.

Regarding vascular pathology, Schneider acknowledged that for many years, the presence of infarcts in brain tissue was not highly regarded as a potential actor for dementia risk, as they were difficult to see on scans. However, the presence of multiple markers was discovered to have an impact.

“If you had a macro infarct and a micro infarct, your odds of getting dementia goes up,” she noted.

In addition, “watershed regions” of the brain bordering those clinicians usually examine to diagnose AD may also be vulnerable, such as those governing blood pressure, and may point toward a dementia diagnosis.

TDP-43 also has been recognized as a particularly significant biomarker, as its presence is related to amnestic dementia, but it mimics dementia found in AD patients, Schneider said. With its strong correlation to cognitive decline due to shrinkage of the hippocampus and its notable presence with AD-related dementia occurring later in life, symptoms of the disease become much more difficult to treat.

Boosting resilience as one ages, Schneider continued, is the best way to fend off more acute arrival of AD symptoms. It is important to focus on lifestyle modifications, such as physical and cognitive activities, diet and neurobehaviors, like managing stress and anxiety and gaining purpose in one’s life. Those, combined with addressing basic health concerns, can be agents of positive change that can lead to lessening pathology at disease onset.

“We have to think about late neurologic changes, because that really accelerates the decline in Alzheimer’s disease,” Schneider said. “We really need to think about resilience because it’s very likely that some of these pathologies change.”