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Sex differences in the relation of mixed TDP‐43 and AD pathologies to risk of dementia and cognitive decline
Author(s) -
Barnes Lisa L.,
Yu Lei,
Kapasi Alifiya,
Lamar Melissa,
Bennett David A.,
Schneider Julie A.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045180
Subject(s) - dementia , episodic memory , cognitive decline , cognition , gerontology , psychology , memory impairment , medicine , demographics , logistic regression , disease , psychiatry , pathology , demography , sociology
Abstract Background It is well‐established that TDP‐43 pathology (also known as LATE) is commonly observed in the brains of older persons, is often mixed with AD pathology, and increases the risk of impairment in episodic memory and Alzheimer’s dementia. It is not known whether there are sex differences in the relation of mixed TDP‐43 and AD pathology with Alzheimer’s dementia and decline in memory. Method We included 1,406 autopsied participants who initially enrolled without dementia from three ongoing epidemiologic longitudinal clinical‐pathologic studies of aging: Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study. Participants underwent annual clinical evaluations for diagnosis of Alzheimer’s dementia, including the administration of seven cognitive tests to create summary measures of episodic memory. Systematic uniform neuropathologic examination quantified TDP‐43, AD, and other age‐related pathologies. Persons were categorized into 4 groups; those with no AD or TDP, ‘pure’ TDP, ‘pure’ AD, and mixed AD/TDP. We conducted mixed effects and logistic regression models controlling for age at death, sex, race, and education with cognitive decline and dementia as outcomes, respectively. Results In fully adjusted models that controlled for demographics and other age‐related pathologies, compared to older persons without AD or TDP‐43 pathology, those having either or both pathologies had faster decline in episodic memory. Further, there was a sex difference such that the association of mixed AD/TDP‐43 on episodic memory decline was stronger in women than in men (b = 0.040, SE = 0.018, p = 0.022). Similarly, compared to those with no AD or TDP, having ‘pure’ TDP (OR = 3.261), ‘pure’ AD (OR = 4.176), or mixed AD/TDP‐43 (OR = 10.342) increased the odds of dementia (all p’s <0.001). However, “pure” TDP‐43 pathology increased the odds of dementia more strongly in men than in women (OR = 1.392, 95% CI: 0.555, 0.012), in fully adjusted models. Conclusion The results suggest sex differences in the effects of mixed AD/TDP‐43 pathology and ‘pure’ TDP pathology on risk of Alzheimer’s dementia and decline in episodic memory. These effects are independent of demographics and other age‐related pathologies.