SuperAgers is a term often used to refer to individuals aged 80 years and over who score similarly to individuals aged 20-30 years their younger in memory tests. Additionally, this group has been shown to exhibit less brain volume loss over time, which could explain why this group remains better protected against dementia.
As we age our memory capacity typically tends to decline. Various health studies have shown that around 40 percent of people aged 65 years and older have age-associated memory impairment, and approximately 1percent of these cases progress into dementia each year.
Studies into how SuperAgers maintain their unique ability in memory capacity despite advancement in age could help researchers develop preventative strategies and treatments for cognitive decline.
To explore this issue in more depth, researchers at Northwestern University in the US state of Chicago, recently autopsied the brains of 24 individuals, including six who were characterized as ‘cognitive SuperAgers’. They found that the neurons (nerve cells) in SuperAgers were larger than in those aged 20–30 years younger, and that neurons of SuperAgers did not have neurofibrillary tangles (NFT), also known as ‘tau tangles’.
These tangles are understood to result from the soluble tau protein in neurons aggregating into insoluble tau protein tangles. For reasons that remain unknown, cell populations in the brain’s entorhinal cortex (ERC) — area in the temporal lobe of the brain associated with memory, navigation and perception of time — are selectively vulnerable to ‘tau tangle’ formation during normal aging and in early stages of Alzheimer’s Disease.
Findings from the study showed neuronal shrinkage (atrophy) in the ERC, which the researchers suggested could be a function of ‘tau tangle’ formation in the affected cells, and which lead to poor memory abilities in older age. They also noted that identifying this contributing factor is crucial for the early identification of Alzheimer’s, monitoring its course, and guiding treatment.
For the study, the researchers autopsied the brains of six SuperAgers with an average age of 91 years; seven ‘cognitively average’ elderly people with an average age of 89 years; six healthy younger adults aged between 26 and 61 years;and five adults with mild cognitive impairment (MCI) at an average age of 92 years.At the time of their death, all participants could perform daily living activities, and all were free from clinical evidence or history of neurological or psychiatric conditions.
The researchers noted no difference in years of education, brain weight, or postmortem interval between the groups. They also tested the groups for ApoE genotypes using DNA from previous blood samples of the deceased. Among the participants, only one person from the MCI group had the APOE-4 allele, a risk factor for Alzheimer’s disease.
During the autopsy the researchers assessed a cross-sectional layer of neurons out of the six layers that comprise ERC. In particular, they assessed overall neuronal health and for the presence of tau proteins that have been implicated in neuronal dysfunction and are among the first markers of Alzheimer’s disease.
The researchers found that layer II ERC neurons were significantly larger in SuperAgers than other groups, including younger controls, some of whom were 60 years their junior. They also found that those in the ‘cognitively average’ group of older individuals had over twice the NFT density of SuperAgers in layer II of the ERC.
Though the study did not come up with any concrete answers on why these neurons were larger in SuperAgers, or why they are relatively protected from disease, one possibility put forward by the researchers was that the greater neuron size protected these cells from neurofibrillary tangles. They also found that this protection appeared to occur despite other age-related brain changes present in SuperAgers
They further explained that larger layer II ERC neurons among SuperAgers than their young peers might indicate that large ERC cells were present from birth and structurally maintained throughout life. The scientists also said that their findings suggest that increased NFT levels lead to neuronal shrinkage. They noted that this observation was particularly apparent in the MCI group, which had a significantly lower cell size than other groups.
On the question of shortcomings in their study, the research team admitted that their results were limited by their small sample size, which they pointed out was largely because of SuperAgers being unique and rare in a population. They added that future in-depth studies were needed to understand why and how some people develop these super-sized cells while others do not.
Taken together, research into neuronal size and related studies can provide improved insights to SuperAgers’ cognitive functionality and relative resistance and/ or resilience to neurodegenerative diseases. These studies could also lead to identifying and developing new interventions that could potentially maintain cognitive function throughout a person’s lifespan.
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