Use of the CDR® plus NACC FTLD in mild FTLD: Data from the ARTFL/LEFFTDS consortium

Miyagawa, Toji; Brushaber, Danielle; Syrjanen, Jeremy; Kremers, Walter K.; Fields, Julie A.; Forsberg, Leah K.; Heuer, Hilary W.; Knopman, David S.; Kornak, John; Boxer, Adam L.; Rosen, Howie; Boeve, Bradley F.; Appleby, Brian S.; Bordelon, Yvette; Bove, Jessica; Brannelly, P; Caso, Christina; Coppola, Giovanni; Dever, Reilly; Dheel, Christina; Dickerson, Bradford C.; Dickinson, Susan; Dominguez, Sophia; Domoto‐Reilly, Kimiko; Faber, Kelley; Ferrell, Jessica; Fishman, Ann; Fong, Jamie; Foroud, Tatiana; Gavrilova, Ralitza H.; Gearhart, Debra; Ghazanfari, Behnaz; Ghoshal, Nupur; Goldman, Jill; Graff‐Radford, Jonathan; Graff‐Radford, Neill R.; Grant, Ian; Grossman, Murray; Haley, Dana; Hsiung, Robin; Huey, Edward D.; Irwin, David J.; Jones, David T.; Jones, Lynne C.; Kantarci, Kejal; Karydas, Anna; Kaufer, Daniel I.; Kerwin, Diana; Kraft, Ruth; Kramer, Joel H.; Kukull, Walter A.; Litvan, Irene; Lucente, Diane; Lungu, Codrin; Mackenzie, Ian R.; Maldonado, Miranda; Manoochehri, Masood; McGinnis, Scott; McKinley, Emily C.; Mendez, Mario F.; Miller, Bruce L.; Multani, Namita; Onyike, Chiadi U.; Padmanabhan, Jaya; Pantelyat, Alexander; Pearlman, Rodney; Petrucelli, Leonard; Potter, Madeline; Rademakers, Rosa; Ramos, Eliana Marisa; Rankin, Kate; Rascovsky, Katya; Roberson, Erik D.; Rogalskı, Emily; Sengdy, Pheth; Shaw, Leslie M.; Tartaglia, Maria Carmela; Tatton, Nadine; Taylor, Joanne; Toga, Arthur W.; Trojanowski, John Q.; Wang, Ping; Weıntraub, Sandra; Wong, Bonnie; Wszołek, Zbigniew K.

doi:10.1016/j.jalz.2019.05.013

Cited by 74 publications

(109 citation statements)

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“…Global cognition was scored using the Mini Mental State Examination (MMSE) and Clinical Dementia Rating scale (CDR) plus FTD modules 26. The Revised Cambridge Behavioural Inventory (CBI-R) was used to measure behavioural changes 27.…”

Section: Methodsmentioning

confidence: 99%

Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia

Ende

Xiao

et al. 2020

J Neurol Neurosurg Psychiatry

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IntroductionSynapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD.MethodsWe included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses.ResultsSymptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301–872)) than presymptomatic carriers (1003 pg/mL (624–1358), p<0.001) and non-carriers (990 pg/mL (597–1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage.DiscussionWe conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.

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Section: Methodsmentioning

confidence: 99%

Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia

Ende

Xiao

et al. 2020

J Neurol Neurosurg Psychiatry

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“…The sample included 100 participants with f-FTLD with a known pathogenic variant ( MAPT + [28 individuals with MAPT pathogenic variants], GRN + [33 individuals with GRN pathogenic variants], and C9orf72 + [39 individuals with C9orf72 repeat expansions]) and 60 family members of known pathogenic variant carriers who did not carry the pathogenic variant (demographic characteristics are listed in the Table and eTable 1 in the Supplement ). Participants with f-FTLD were grouped into the following 3 disease stages using CDR + NACC FTLD 27 : presymptomatic (CDR + NACC FTLD = 0 [n = 57]), mild or questionable (CDR + NACC FTLD = 0.5 [n = 15]), or symptomatic (CDR + NACC FTLD = ≥1 [n = 28]). Included were participants who had at least 2 structural magnetic resonance images within 1 of these stages ( Table and eTable 1 in the Supplement ); all available scans within that disease stage for each participant were used for the study.…”

Section: Methodsmentioning

confidence: 99%

“…Neuropsychological tests included the Uniform Data Set (version 3.0) neuropsychological battery. 28 Functional status was quantified using CDR + NACC FTLD 27 , 29 , 30 (details are provided in the Supplement ). Brain imaging was not used for diagnosis or severity rating.…”

Section: Methodsmentioning

confidence: 99%

Rates of Brain Atrophy Across Disease Stages in Familial Frontotemporal Dementia Associated With MAPT, GRN, and C9orf72 Pathogenic Variants

et al. 2020

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“…Individuals were assessed for the presence or absence of symptoms and symptom severity using the eight‐item Clinical Dementia Rating (CDR) plus National Alzheimer's Coordinating Center (NACC) FTLD CDR ® plus NACC FTLD scale, 25 which is a modification of the standard CDR scale 26 . The CDR combines structured information gathered from both the patient and a knowledgeable informant.…”

Section: Methodsmentioning

confidence: 99%

“…It has been used widely in a variety of clinical and research settings including clinical trials in AD treatments 27 . The Behavior/Comportment and Language domains were added to the original CDR to address the variable clinical presentations typical of familial FTLD 25 . Individuals were classified based on CDR ® plus NACC FTLD as asymptomatic (CDR ® plus NACC FTLD = 0), questionable/mild cognitive or behavioral changes (CDR ® plus NACC FTLD = 0.5), mild dementia (CDR ® plus NACC FTLD = 1.0), and moderate to severe dementia (CDR ® plus NACC FTLD>1).…”

Section: Methodsmentioning

confidence: 99%

Quality of life and caregiver burden in familial frontotemporal lobar degeneration: Analyses of symptomatic and asymptomatic individuals within the LEFFTDS cohort

Gentry¹,

Lapid²,

Syrjanen³

et al. 2020

Alzheimer's & Dementia

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Objective The Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects evaluates familial frontotemporal lobar degeneration (FTLD) kindreds with MAPT, GRN, or C9orf72 mutations. Objectives were to examine whether health‐related quality of life (HRQoL) correlates with clinical symptoms and caregiver burden, and whether self‐rated and informant‐rated HRQoL would correlate with each other. Methods Individuals were classified using the Clinical Dementia Rating (CDR®) Scale plus National Alzheimer's Coordinating Center (NACC) FTLD. HRQoL was measured with DEMQOL and DEMQOL‐proxy; caregiver burden with the Zarit Burden Interview (ZBI). For analysis, Pearson correlations and weighted kappa statistics were calculated. Results The cohort of 312 individuals included symptomatic and asymptomatic individuals. CDR® plus NACC FTLD was negatively correlated with DEMQOL (r = −0.20, P = .001), as were ZBI and DEMQOL (r = −0.22, P = .0009). There was fair agreement between subject and informant DEMQOL (κ = 0.36, P <.0001). Conclusion Lower HRQoL was associated with higher cognitive/behavior impairment and higher caregiver burden. These findings demonstrate the negative impact of FTLD on individuals and caregivers.

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Use of the CDR® plus NACC FTLD in mild FTLD: Data from the ARTFL/LEFFTDS consortium

Cited by 74 publications

References 30 publications

Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia

Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia

Rates of Brain Atrophy Across Disease Stages in Familial Frontotemporal Dementia Associated With MAPT, GRN, and C9orf72 Pathogenic Variants

Quality of life and caregiver burden in familial frontotemporal lobar degeneration: Analyses of symptomatic and asymptomatic individuals within the LEFFTDS cohort

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