Paucity of Entorhinal Cortex Pathology of the Alzheimer’s Type in SuperAgers with Superior Memory Performance

Abstract

Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer’s disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20–30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P < 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers.

Reaching the Goal: Superior Navigators in Late Adulthood Provide a Novel Perspective into Successful Cognitive Aging

“…Furthermore, they have fewer neurofibrillary tangles in the EC by three-fold, compared to age-matched cognitively normal older adults, and by 100-fold, compared to AD patients. These observations hint at a better maintenance of the EC in this cohort (Gefen et al, 2021).…”

Dihydromyricetin Improves Cognitive Impairments in d‐Galactose‐Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase

“…Brain scans showed that neurofibrillary tangles and amyloid plaques were the main features of AD patients. [ 24 ] Gefen et al. found that fibrous tangles in the brain were more toxic than amyloid plaques in leading to dementia.…”

“…found that fibrous tangles in the brain were more toxic than amyloid plaques in leading to dementia. [ 24,25 ] The end result of tangles formation is cell death. [ 26 ] In the hippocampus of AD patients, the increase of neurofibrillary tangles is usually accompanied with the decrease of neurons.…”

“…[ 23 ] Oxidative stress plays an important role in the aging and neurodegenerative process, which may lead to severe neurological disorders in brain. [ 33,34,21–32,35,36 ] MDA is a key index of lipid peroxidation induced by oxidative damage. Glutathione peroxidase (GSH‐PX) can remove lipid peroxides induced by ROS.…”

Defining exceptional cognition in older adults: A systematic review of cognitive super‐ageing

“…Imaging studies of the brains of super‐agers have demonstrated less cortical atrophy, differences in functional connectivity, greater white matter integrity and a reduced burden of positron emission tomography (PET) amyloid and tau compared with control participants 5,19–22 . Neuropathological studies have reported less but still significant Alzheimer's type pathology 17,23,24 . This suggests that some factors associated with super‐ageing status are modifiable and that mechanisms of both resistance and resilience to neurodegenerative pathology involving brain reserve and cognitive reserve processes 25 may underly exceptional cognition at older ages.…”