Comorbid neuropathologies have major impact on cognition

By Eleanor McDermid

Cognitive impairment is most likely to affect people with multiple types of brain pathology, irrespective of which particular pathologies they have, a study shows.

"Such comorbidity might confound clinical research and the assembling of representative or homogeneous cohorts, as needed for meaningful clinical trials", say Lon White (University of Hawaii John A Burns School of Medicine, Honolulu) and co-researchers.

The findings arise from an analysis of 334 women from the Nun Study (NS) and 774 men from the Honolulu-Asia Aging Study (HAAS), who all undertook regular cognitive screening in life and were autopsied at death.

Alzheimer's disease (AD) pathology was the most common type of neuropathology overall, affecting 39% of NS participants and 43% of HAAS participants. However, the researchers stress that "most of the [cognitively] impaired participants had lesion mixtures that included few or no AD abnormalities".

Low brain weight and hippocampal sclerosis was present in similar proportions of the participants of both studies, but microinfarcts were significantly more common in the HAAS men than the NS women, while neocortical Lewy body pathology was more severe in the NS women.

The neuropathologies were present at expected levels, in "nearly all possible combinations", the team reports in Neurology.

For each pathology, its presence and severity significantly increased the likelihood of impaired cognitive performance at last assessment, with increases ranging from about two- to 10-fold.

But accounting for multiple pathologies had a "dramatic" effect. NS women in the highest category for number and severity of neuropathologies had a 99.1-fold increased likelihood of cognitive impairment, relative to those with no neuropathology, while HAAS men had a 37.6-fold increase.

The effect of multiple neuropathologies "was unrelated to the types of lesion involved, including those of AD", observe White et al.

They add: "While not of great importance for most younger persons, high levels of comorbidity may be fundamental to late-life frailty and to aging itself."

The team also found that the effects of multiple neuropathologies may account for the phenomenon of "cognitive resilience", in which people are cognitively normal or only mildly impaired, despite significant AD pathology.

There were 44 NS participants and 121 HAAS participants with Braak stage V pathology, and around a third of those tested less than 4 years before death had apparent cognitive resilience. In both cohorts, having few or no non-AD pathologies was significantly associated with cognitive resilience, with younger age at death also contributing.

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