Citations 2
Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective
Aggarwal, Neelum T. , Vila‐Castelar, Clara , Brugulat‐Serrat, Anna , Foldi, Nancy S. , Gilsanz, Paola , Li, Wei , McManus, Alison J. , Lent, Debora Melo van , Milani, Sadaf Arefi , Shaaban, C. Elizabeth , Stites, Shana D. , Trani, Jean‐Francoise, Turner, Arlener D. , Vonk, Jet M. J. , Quiroz, Yakeel T. , Group, for the Diversity and Disparity Professional Interest Area Sex and Gender Special Interest, Mielke, Michelle M. , Agarwal, Puja , Arenaza‐Urquijo, Eider M. , Brett, Benjamin L. , DuBose, Lyndsey Elisabeth , Eikelboom, Willem S. , Flatt, Jason D. , Franzen, Sanne , Sundermann, Erin E. , Suryadevara, Vidyani , Babulal, Ganesh M. , Group, for the Diversity and Disparity Professional Interest Area Sex and Gender Special Interest
Alzheimer's & Dementia | April 8, 2022 | Volume: 18 | Issue: 12 | Pages: 2707-2724
Abstract Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. Highlights The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.
Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers
Meeter, Lieke , Sias, Ana C. , Jiskoot, Lize C. , Kaat, Laura Donker , Papma, Janne M., Panman, Jessica , Ende, Emma L. van der , Dopper, Elise G.P. , Graff, Caroline , Boxer, Adam L. , Rosen, Howard J., Sánchez‐Valle, Raquel , Galimberti, Daniela , Pijnenburg, Yolande A.L. , Benussi, Luisa , Ghidoni, Roberta , Borroni, Barbara , Laforce, Robert , Campo, Marta del , Teunissen, Charlotte E. , Minkelen, Rick van , Coppola, Giovanni , Geschwind, Dan, Rademakers, Rosa , Karydas, Anna M., Öijerstedt, Linn , Binetti, Giuliano , Padovani, Alessandro , Cash, David M. , Dick, Katrina M., Bocchetta, Martina , Rohrer, Jonathan D. , Petrucelli, Leonard , Lee, Suzee E. , Gendron, Tania F. , Del Campo, Marta , Teunissen, Charlotte E , Sánchez-Valle, Raquel , Rohrer, Jonathan D , Russo, Silvia P. , Papma, Janne M. , Franzen, Sanne , Rojas, Julio C. , Scarpini, Elio , Miller, Bruce L. , Swieten, John C. van , Padovani, Alessandro , Cash, David M , Donker Kaat, Laura , Dopper, Elise G P , Galimberti, Daniela , Bocchetta, Martina , Pijnenburg, Yolande A L , Jiskoot, Lize C , Laforce, Robert , Graff, Caroline , Borroni, Barbara
Annals of Clinical and Translational Neurology | April 10, 2018 | Volume: 5 | Issue: 5 | Pages: 583-597
AbstractObjectiveTo evaluate poly(GP), a dipeptide repeat protein, and neurofilament light chain (NfL) as biomarkers in presymptomatic C9orf72 repeat expansion carriers and patients with C9orf72‐associated frontotemporal dementia. Additionally, to investigate the relationship of poly(GP) with indicators of neurodegeneration as measured by NfL and grey matter volume.MethodsWe measured poly(GP) and NfL levels in cerebrospinal fluid (CSF) from 25 presymptomatic C9orf72 expansion carriers, 64 symptomatic expansion carriers with dementia, and 12 noncarriers. We explored associations with grey matter volumes using region of interest and voxel‐wise analyses.ResultsPoly(GP) was present in C9orf72 expansion carriers and absent in noncarriers (specificity 100%, sensitivity 97%). Presymptomatic carriers had lower poly(GP) levels than symptomatic carriers. NfL levels were higher in symptomatic carriers than in presymptomatic carriers and healthy noncarriers. NfL was highest in patients with concomitant motor neuron disease, and correlated with disease severity and survival. Associations between poly(GP) levels and small grey matter regions emerged but did not survive multiple comparison correction, while higher NfL levels were associated with atrophy in frontotemporoparietal cortices and the thalamus.InterpretationThis study of C9orf72 expansion carriers reveals that: (1) poly(GP) levels discriminate presymptomatic and symptomatic expansion carriers from noncarriers, but are not associated with indicators of neurodegeneration; and (2) NfL levels are associated with grey matter atrophy, disease severity, and shorter survival. Together, poly(GP) and NfL show promise as complementary biomarkers for clinical trials for C9orf72‐associated frontotemporal dementia, with poly(GP) as a potential marker for target engagement and NfL as a marker of disease activity and progression.