Neuropathological Features of Age-Related Brain Diseases

As we age, the structure and function of our brains can change, which may contribute to cognitive decline. 

Analysis of donated brains from 100 centenarians and 297 nonagenarians from the 90+ Study, allowed to compare the prevalence of 10 neuropathological changes related to dementia and cognitive performance.

The figure graphically represents the prevalence of the individual dichotomized neuropathological changes in nonagenarians and centenarians. Compared with nonagenarians, centenarians had equal or slightly higher but not significant prevalence of all 10 individual neuropathological changes except large infarcts. Panel B shows the prevalence of the 10 neuropathological changes in centenarians and nonagenarians 
and the odds of dementia associated with these changes.

Among centenarians, the most common neuropathological change was arteriolosclerosis (88%), followed by ADNC (Alzheimer's disease neuropathological change: 75%) and ARTAG (Age-related tau astrogliopathy: 66%). Among other vascular neuropathological changes, CAA (cerebral amyloid angiopathy) was most common (54%), with atherosclerosis present in 7%, microinfarcts in 5%, and large infarcts in 1%. LATE-NC (Limbic-predominant age-related TDP-43 encephalopathy neuropathological change) was present in 42%, LBD (Lewy body disease) in 22%, and HS (hippocampal sclerosis) in 15%. Among nonagenarians, the ordering of prevalence of neuropathological change was the same as centenarians: arteriolosclerosis (81%), followed by ADNC (71%), ARTAG (61%), CAA (55%), LATE-NC (34%), LBD (22%), and HS (11%). 

The odds of dementia associated with individual neuropathological changes did not differ significantly between centenarians and nonagenarians. However, centenarians had a pattern of higher odds of dementia for all neuropathological changes except microinfarcts and LBD compared with nonagenarians.  

Lewy body disease is characterized by the presence of abnormal protein deposits in the brain called Lewy bodies, which can lead to cognitive impairment and movement problems. Alzheimer's disease, on the other hand, is characterized by the accumulation of beta-amyloid plaques and tau tangles in the brain, which can also lead to cognitive impairment. Limbic-predominant age-related TDP-43 encephalopathy neuropathological change is a condition in which there is abnormal accumulation of a protein called TDP-43 in the limbic system of the brain, leading to cognitive and behavioral changes. Hippocampal sclerosis is a condition in which there is loss of neurons in the hippocampus, a region of the brain important for memory, which can also lead to cognitive impairment. Atherosclerosis is a disease of the blood vessels, in which the walls of the arteries become thickened and narrowed, leading to reduced blood flow to the brain and other organs. Microinfarcts are small, subclinical areas of brain damage caused by tiny blockages in the small blood vessels that supply blood to the brain. They are thought to result from age-related changes in the blood vessels, such as atherosclerosis and reduced blood flow. Microinfarcts are often asymptomatic and go unnoticed.


Neuville RS, Biswas R, Ho CC, Bukhari S, Sajjadi SA, Paganini-Hill A, Montine TJ, Corrada MM, Kawas CH. Study of neuropathological changes and dementia in 100 centenarians in The 90+ Study. Alzheimers Dement. 2023 Feb 16. doi: 10.1002/alz.12981. Epub ahead of print. PMID: 36795955.


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