Objective: To assess whether co-pathologies and clinical phenotypes in people with four-repeat tauopathies (progressive supranuclear palsy [PSP], corticobasal degeneration [CBD]) differ by sex.

Background: PSP and CBD are associated with overlapping clinical phenotypes, including PSP, corticobasal syndrome (CBS), primary progressive aphasia (PPA), Alzheimer’s (AD), and Lewy body diseases. These phenotypes can also occur in association with other pathologies, limiting the clinical ability for predicting underlying pathology. Sex impacts co-pathology presence and severity, and clinical phenotypes in other more common neurodegenerative diseases, although PSP and CBD are studied less.

Method: National Alzheimer’s Coordinating Center data for people with PSP (77 females, 98 males) and CBD (50 females, 64 males) pathology were used. Sex differences within each group were assessed with generalized linear models for clinical diagnoses, behavioral and motor symptoms correcting for age at last visit; cognitive symptoms correcting for age at last visit and education; co-pathologies correcting for age at death. Co-pathologies included frontotemporal lobar degeneration (FTLD)-3R tau pathology, FTLD-TDP-43 pathology, amyotrophic lateral sclerosis/motor neuron disease, other FTLD pathology, hippocampal sclerosis, ischemic/hemorrhagic/vascular pathology, aging-related tau astrogliopathy, AD pathology, Lewy body pathology, substantia nigra neuron loss, and cerebral amyloid angiopathy.

Results: Sex distribution across PSP and CBD groups were similar. Co-pathologies did not differ by sex. For PSP group, PSP was the most common clinical diagnosis (41%) without sex differences. Compared to males with PSP, females were less likely to have memory, orientation, judgment, attention impairments and had less severe dementia. For CBD group, unspecified frontotemporal dementia was the most common clinical diagnosis (36%) followed by CBS (25%) without sex differences. Compared to males with CBD, females were less likely to have apathy, tremors, and were older at behavioral symptom onset.

Conclusion: There were no sex differences for clinical diagnoses or co-pathologies in PSP and CBD. However, females may have a clinical advantage with less cognitive decline in PSP, lower likelihood of apathy, tremors and later onset of behavioral changes in CBD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-comparisons-for-co-pathologies-and-clinical-phenotypes-in-autopsy-confirmed-four-repeat-tauopathies/