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Plasma neurofilament light chain levels reflect caregiver burden and social cognition measures in familial frontotemporal lobar degeneration (FTLD)
Author(s) -
Heuer Hilary W.,
Rojas Julio C.,
Toller Gianina,
Rankin Katherine,
Brushaber Danielle,
Appleby Brian,
Bordelon Yvette M.,
Dickerson Brad C.,
Kimiko DomotoReilly,
Faber Kelley,
Foroud Tatiana M.,
Forsberg Leah K,
Ghoshal Nupur,
Grant Ian,
GraffRadford Neill R.,
Grossman Murray,
Hsiung GingYuek Robin,
Huey Edward D.,
Karydas Anna M.,
Kaufer Daniel,
Kerwin Diana R.,
Lagone Emma,
Litvan Irene,
Ljubenkov Peter A.,
Mackenzie Ian R.,
Mendez Mario F.,
Miller Bruce L.,
Onyike Chiadi U.,
Ramos Eliana Marisa,
Rascovsky Katya,
Roberson Erik D.,
Tartaglia Carmela,
Weintraub Sandra,
Boeve Bradley F.,
Rosen Howard J.,
Boxer Adam L.
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.046247
Subject(s) - frontotemporal lobar degeneration , asymptomatic , dementia , cognition , psychology , c9orf72 , medicine , frontotemporal dementia , disease , clinical psychology , oncology , psychiatry
Abstract Background Plasma NfL is a sensitive marker of axonal injury that is elevated in symptomatic FTLD and asymptomatic carriers of FTLD‐associated genetic mutations at short‐term risk of phenoconversion to mild behavioral or cognitive impairment or dementia. In carriers of FTLD‐associated genetic mutations, NfL is associated with clinical measures of disease severity. Method Plasma NfL was measured using single molecule array technology in baseline blood samples from 290 participants in the ARTFL/LEFFTDS consortia. Participants included 181 asymptomatic mutation carriers ( C9orf72 , GRN , and MAPT ); 45 with mild impairment (MBI/MCI), and 64 with dementia. 103 family members without FTLD‐associated mutations served as asymptomatic controls. Social cognition scales were obtained through clinical evaluation at baseline, year 1, and year 2. Stepwise linear regressions assessed NfL relationships with baseline social cognition measures. Linear mixed models were used to test the ability of baseline NfL to predict longitudinal changes. Analyses corrected for age, sex, and genotype. Result At baseline, plasma NfL correlated with all measures of social cognition, regardless of genotype. Associations were strongest for the Revised Self‐monitoring Scale (RSMS;β = ‐.50, p < .001), total score of the Social Norms questionnaire (β= .48, p < .001), and caregiver burden (Zarit burden;β = .55, p < .001). Regardless of disease severity, baseline NfL related to worse RSMS scores over time (‐3.7 points at year 2/ LogNfL unit increase, 95% CI ‐1.7 to ‐5.7, p < .001). In MBI/MCI, higher baseline NfL was associated with worse longitudinal scores on the Social Norms questionnaire (‐5.9 points at year 2/LogNfL unit increase, 95% CI ‐1.1 to ‐10.7, p = .016). No associations were seen in asymptomatic non‐carriers. Conclusion In this familial FTLD cohort, plasma NfL is correlated with clinical measures of social cognition and caregiver burden. Higher baseline plasma NfL concentrations are associated with worsening self‐monitoring and social norms scores over time. These associations suggest that NfL is correlated with clinically meaningful measures that may be relevant to therapeutic development.