Challenges Remain in Defining Normal, Pathological Brain Aging

the Neurology Advisor take:

Markers of Alzheimer’s disease (AD) are present in approximately 83% of adults by age 89, blurring the distinction between normal and pathological brain aging, according to an article published in The Lancet Neurology.

It is now widely accepted that biomarkers of Alzheimer’s disease become abnormal long before clinical symptoms manifest, which has led to the formulation of research guidelines for preclinical AD by expert panels such as the National Institute on Aging – Alzheimer’s Association (NIA-AA).

The guidelines set forth by the NIA-AA do not classify asymptomatic adults who have neurodegenerative changes in the absence of amyloidosis. To bridge this gap, researchers proposed a complementary, two-feature biomarker classification system. Thus, each patient is labeled as positive or negative for cerebral amyloidosis (A) and neurodegeneration (N), resulting in four distinct groups: A^-N^-, A^-N⁺, A⁺N^- and A⁺N⁺.

Researchers assessed age-specific frequencies of these four groups among a sample of 985 asymptomatic adults aged 50-89. The estimated population frequency of A^-N^- was 100% at age 50, but decreased to 17% by age 89. The frequency of A^-N⁺ increased from age 60 years to 24% (16–34) by age 89, whereas that of A⁺N^- increased to 28% (24–32) by age 74 years and then decreased to 17% (11–25) by age 89 years. The frequency of A⁺N⁺ increased from age 65 to 42% (31–52) by age 89.

The study highlights the difficulty between distinguishing normal and pathological aging. This could imply that normal aging may be better defined as the ability to maintain optimum cognitive function despite harboring pathogenic brain lesions.