Older individuals experiencing a faster reduction in the volume of the hippocampus region of the brain also exhibited quicker cognitive decline, according to new research. This correlation did not rely on the accumulation of abnormal proteins in the brain. The findings were published in the journal Neurology.
Cognitive abilities undergo significant changes throughout the human lifespan. In childhood, these skills develop rapidly, while in adulthood, they generally stabilize. Typically, humans reach their peak cognitive performance in their late 20s to early 30s. As adults transition into middle age and beyond, some cognitive functions, such as processing speed and memory, begin to decline.
In individuals with Alzheimer’s disease, cognitive decline occurs as abnormal proteins accumulate in the brain. These proteins form clumps that gradually destroy neurons in affected brain areas, leading to cognitive deterioration. Neuroimaging can detect this as a reduction in the volume of the neuron mass in affected areas. Recent studies have shown that such brain atrophy is not exclusive to Alzheimer’s disease; other conditions that cause cognitive decline also involve reductions in neuron mass.
Study author Bernard J. Hanseeuw and his colleagues aimed to observe how the volumes of various brain areas and other neuroimaging indicators change over time in older adults, and whether these changes are associated with cognitive decline.
The researchers analyzed data from the Harvard Aging Brain Study, a longitudinal aging study conducted at Massachusetts General Hospital. The study included participants aged between 60 and 90 years who did not have dementia or visible cognitive impairments at the onset.
This analysis involved data from 128 participants who underwent at least two positron emission tomography (PET) scans to assess tau protein concentrations (using Flortaucipir tracer), two scans assessing amyloid-beta plaques (using Pittsburgh Compound B tracer), and two magnetic resonance imaging scans to evaluate changes in specific brain volumes.
Positron emission tomography, or PET, is a diagnostic imaging technique that uses radioactive substances, known as tracers, to visualize and measure metabolic processes within the body. Tau protein normally helps stabilize the internal structures of brain cells. However, in certain medical conditions, it forms tangles that disrupt brain function. Amyloid-beta plaques are clusters of protein that form around brain cells, obstructing normal cell functions. Both are found in Alzheimer’s disease and contribute to the death of neighboring neural cells.
In addition to these scans, study participants completed a battery of cognitive assessments annually. These tests measured episodic memory, executive function, processing speed, and language.
The results indicated that at the start of the study, 73% of participants had low levels of amyloid plaques, while 27% had high levels. Participants with high amyloid plaque levels tended to have lower hippocampal volumes, more areas showing damage to white matter, and higher accumulations of tau protein.
As the study progressed, these indicators, along with the total volume of the cortex and cognitive abilities, worsened in both groups (those with high and low levels of amyloid plaque at the start). However, the decline was more rapid in participants who initially had more amyloid plaque.
The decline in cognitive ability was associated with a reduction in hippocampal volume and an increase in tau protein levels. Changes in the volume of the brain cortex were strongly linked to changes in the thickness of the brain area known as the precuneus, as well as to hippocampal volume. However, the relationship between changes in cortex volume and cognitive ability was very weak and entirely explained by changes in hippocampal volume.
“In this longitudinal study of clinically normal older adults, we observed that decline in cognition after a ten-year follow-up resulted (1) from successive changes in Aβ [amyloid beta] and tau in the neocortex, and (2) from medial temporal lobe pathologies, including entorhinal tauopathy [accumulation of abnormal tau protein in the entorhinal cortex, a region of the brain critical for memory], leading to hippocampal atrophy. Cerebrovascular disease, as measured using WMH [white matter hypointensities, an indicator of damage to white matter of the brain], did not contribute much to cognitive decline,” the study authors concluded.
The study sheds light on the links between changes in the brain and cognitive decline. But it also has limitations that need to be taken into account. Notably, most of the study participants were highly educated and the authors report that results were mainly driven by a few participants who developed cognitive impairments or dementia. However, the removal of these individuals did not change the conclusions, although it somewhat reduced the strength of the observed associations.
The paper, “Association of pathological and volumetric biomarker changes with cognitive decline in clinically normal adults: Harvard Aging Brain Study,” was authored by Bernard J Hanseeuw, Heidi I Jacobs, Aaron P Schultz, Rachel F Buckley, Michelle E Farrell, Nicolas J Guehl, John A Becker, Michael Properzi, Justin S Sanchez, Yakeel T Quiroz, Patrizia Vannini, Jorge Sepulcre, Hyun-Sik Yang, Jasmeer P Chhatwal, Jennifer Gatchel, Gad A Marshall, Rebecca Amariglio, Kathryn Papp, Dorene M Rentz, Marc Normandin, Julie C Price, Brian C Healy, Georges El Fakhri, Reisa A Sperling, and Keith A Johnson.
