Objective: To assess sex differences for cerebrospinal fluid (CSF) phosphorylated tau (p-tau) association with cognition in Parkinson’s disease (PD)

Background: Tau biomarkers can predict cognitive decline and have prognostic value for cognition in PD [1,2]. In Alzheimer’s disease, tau association with verbal memory is stronger in women compared to men before dementia onset [3], implicating a sex difference for the predictive and prognostic value of p-tau. In Lewy body dementia, tau pathology association with dementia severity is stronger for women than men [4], and this sex difference can be present for CSF p-tau before the onset of dementia.

Method: Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI) for 423 individuals (146 women, 277 men) with newly diagnosed PD [5,6]. Montreal Cognitive Assessment for global cognition, Hopkins Verbal Learning Test-immediate and delayed recall for verbal learning and memory, Benton Judgment of Line Orientation for visuospatial function, semantic fluency for language, Letter Number Sequencing for working memory and Symbol Digit Modalities Test for processing speed were included. Sex differences for CSF p-tau associations with cognition was assessed using baseline cognitive scores as outcome, age and education as covariates in linear models.

Results: Age and education were similar for women and men. Women had higher global cognition, verbal learning and memory, language and processing speed scores (p<.007 for all). Men had higher visuospatial function scores (p<.001). Women and men had similar CSF p-tau levels. There was a sex difference for CSF p-tau association with global cognition, verbal learning and memory, visuospatial function, language and processing speed (p<.044 for all). Parameter estimates showed significant associations between higher CSF p-tau and lower delayed recall, visuospatial function, language specifically for women (p≤.047 for all).

Conclusion: In newly diagnosed individuals with PD, tau association with cognition appears to be sex dependent. Sex differences for cognitive scores and sex differences for tau associations with the same cognitive domains suggest that tau may play a role in the differences observed across women and men with PD. Longitudinal models can help determine the sex-specific prognostic and predictive value of tau biomarkers in Lewy body disorders.

References: 1. Gonzalez MC, Ashton NJ, Gomes BF, Tovar-Rios DA, Blanc F, Karikari TK, et al. Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies. JAMA Neurol. 2022;79(1):32–7.
2. Liu C, Cholerton B, Shi M, Ginghina C, Cain KC, Auinger P, et al. CSF tau and tau/Aβ42 predict cognitive decline in Parkinson’s disease. Parkinsonism Relat Disord. 2015 Mar 1;21(3):271–6.
3. Banks SJ, Andrews MJ, Digma L, Madsen J, Reas ET, Caldwell JZK, et al. Sex differences in Alzheimer’s disease: do differences in tau explain the verbal memory gap? Neurobiol Aging. 2021 Nov 1;107:70–7.
4. Bayram E, Coughlin DG, Banks SJ, Litvan I. Sex differences for phenotype in pathologically defined dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2021 Jul 9;92(7):745–50.
5. Marek K, Jennings D, Lasch S, Siderowf A, Tanner C, Simuni T, et al. The Parkinson Progression Marker Initiative (PPMI). Progress in Neurobiology Pergamon; Dec 1, 2011 p. 629–35.
6. Marek K, Chowdhury S, Siderowf A, Lasch S, Coffey CS, Caspell-Garcia C, et al. The Parkinson’s progression markers initiative (PPMI) – establishing a PD biomarker cohort. Ann Clin Transl Neurol. 2018 Dec 1;5(12):1460–77.
Acknowledgments: Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/access-dataspecimens/download-data). For up-to-date information on the study, visit ppmi-info.org.
PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, Acurex Therapeutics, Allergan, Amathus Therapeutics, ASAP, Avid Radiopharmaceuticals, Bial Biotech, Biogen, Biolegend, Bristol Myers Squibb, Calico, Celgene, Cerevel, Coave Therapeutics, Dacapo Brainscience, Denali, Edmond J. Safra Philanthropic Foundation, 4D Pharma PLC, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, Yumanity Therapeutics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-differences-for-tau-association-with-cognition-in-early-parkinsons-disease/