Abstract
| Original language | English |
|---|---|
| Journal | Alzheimer's Dementia |
| DOIs | |
| Publication status | E-pub ahead of print - Dec 14 2020 |
Keywords
- apathy
- cognitive decline
- genetic frontotemporal dementia
- longitudinal design
- MRI
- presymptomatic carriers
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Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes : Alzheimer's and Dementia. / Malpetti, M.; Jones, P.S.; Tsvetanov, K.A.; Rittman, T.; van Swieten, J.C.; Borroni, B.; Sanchez-Valle, R.; Moreno, F.; Laforce, R.; Graff, C.; Synofzik, M.; Galimberti, D.; Masellis, M.; Tartaglia, M.C.; Finger, E.; Vandenberghe, R.; de Mendonça, A.; Tagliavini, F.; Santana, I.; Ducharme, S.; Butler, C.R.; Gerhard, A.; Levin, J.; Danek, A.; Otto, M.; Frisoni, G.B.; Ghidoni, R.; Sorbi, S.; Heller, C.; Todd, E.G.; Bocchetta, M.; Cash, D.M.; Convery, R.S.; Peakman, G.; Moore, K.M.; Rohrer, J.D.; Kievit, R.A.; Rowe, J.B.; (GENFI), on behalf of the Genetic FTD Initiative.
In: Alzheimer's Dementia, 14.12.2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes
T2 - Alzheimer's and Dementia
AU - Malpetti, M.
AU - Jones, P.S.
AU - Tsvetanov, K.A.
AU - Rittman, T.
AU - van Swieten, J.C.
AU - Borroni, B.
AU - Sanchez-Valle, R.
AU - Moreno, F.
AU - Laforce, R.
AU - Graff, C.
AU - Synofzik, M.
AU - Galimberti, D.
AU - Masellis, M.
AU - Tartaglia, M.C.
AU - Finger, E.
AU - Vandenberghe, R.
AU - de Mendonça, A.
AU - Tagliavini, F.
AU - Santana, I.
AU - Ducharme, S.
AU - Butler, C.R.
AU - Gerhard, A.
AU - Levin, J.
AU - Danek, A.
AU - Otto, M.
AU - Frisoni, G.B.
AU - Ghidoni, R.
AU - Sorbi, S.
AU - Heller, C.
AU - Todd, E.G.
AU - Bocchetta, M.
AU - Cash, D.M.
AU - Convery, R.S.
AU - Peakman, G.
AU - Moore, K.M.
AU - Rohrer, J.D.
AU - Kievit, R.A.
AU - Rowe, J.B.
AU - (GENFI), on behalf of the Genetic FTD Initiative
N1 - Export Date: 22 February 2021 Correspondence Address: Rowe, J.B.; Department of Clinical Neurosciences, United Kingdom; email: james.rowe@mrc-cbu.cam.ac.uk Correspondence Address: Rowe, J.B.; MRC Cognition and Brain Sciences Unit, United Kingdom; email: james.rowe@mrc-cbu.cam.ac.uk Funding details: Wellcome Trust, WT, MR/T033371/1, SUAG051/G101400, 103838 Funding details: Alzheimer's Society, AS‐JF‐19a‐004‐517 Funding details: Medical Research Council, MRC, MR/M008525/1 Funding details: EU Joint Programme – Neurodegenerative Disease Research, JPND Funding details: UK Dementia Research Institute, UK DRI Funding details: Sidney Sussex College, University of Cambridge Funding details: Eli Lilly and Company Funding details: NIHR Cambridge Biomedical Research Centre Funding details: British Academy, PF160048, 101149 Funding details: Biogen Funding details: BRC149/NS/MH Funding details: National Institute for Health Research, NIHR Funding details: Janssen Biotech Funding details: Canadian Institutes of Health Research, CIHR Funding details: Medical Research Council, MRC, SUAG/047/G101400 Funding details: MR/M023664/1 Funding text 1: This work is co‐funded by the UK Medical Research Council (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and the Bluefield Project, as well as a JPND grant “GENFI‐prox” (by DLR/BMBF to MS, joined with JDR, JvS, MO, BB and CG). MM is supported by the Cambridge Trust & Sidney Sussex College Scholarship. PSJ is supported by the Cambridge Centre for Parkinson Plus. KAT is supported by the British Academy Postdoctoral Fellowship (KAT: PF160048) and Guarantors of Brain (KAT: 101149). TR is supported by the Cambridge Centre for Parkinson Plus and Cambridge Biomedical Resource Centre. RAK is supported by Medical Research Council (RAK: SUAG/047/G101400). JBR reports grants from the NIHR Cambridge Biomedical research centre, Wellcome Trust (103838), and Medical Research Council (SUAG051/G101400; MR/T033371/1); personal fees from Asceneuron, WAVE, Astex, and Biogen; and grants from Janssen, AZ Medimmune, and Eli Lilly, outside the submitted work. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS‐JF‐19a‐004‐517), and by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. References: Rascovsky, K., Hodges, J.R., Knopman, D., Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia (2011) Brain, 134, pp. 2456-2477; Coyle-Gilchrist, I.T.S., Dick, K.M., Patterson, K., Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes (2016) Neurology, 86, pp. 1736-1743; Lansdall, C.J., Coyle-Gilchrist, I.T.S., Jones, P.S., Apathy and impulsivity in frontotemporal lobar degeneration syndromes (2017) Brain, 140, pp. 1792-1807; Chow, T.W., Binns, M.A., Cummings, J.L., Apathy symptom profile and behavioral associations in frontotemporal dementia vs dementia of Alzheimer type (2009) Arch Neurol, 66, pp. 888-893; Lansdall, C.J., Coyle-Gilchrist, I.T.S., Vázquez Rodríguez, P., Prognostic importance of apathy in syndromes associated with frontotemporal lobar degeneration (2019) Neurology, 92, pp. e1547-e1557; Josephs, K.A., Jr., Whitwell, J.L., Weigand, S.D., Predicting functional decline in behavioural variant frontotemporal dementia (2011) Brain, 134, pp. 432-448; O'Connor, C.M., Landin-Romero, R., Clemson, L., Behavioral-variant frontotemporal dementia: distinct phenotypes with unique functional profiles (2017) Neurology, 89, pp. 570-577; Kipps, C.M., Mioshi, E., Hodges, J.R., Emotion, social functioning and activities of daily living in frontotemporal dementia (2009) Neurocase, 15, pp. 182-189; O'Connor, C.M., Clemson, L., Hornberger, M., Longitudinal change in everyday function and behavioral symptoms in frontotemporal dementia (2016) Neurol Clin Pract, 6, pp. 419-428; Murley, A.G., Coyle-Gilchrist, I., Rouse, M.A., Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes (2020) Brain, 143, pp. 1555-1571; Rosen, H.J., Allison, S.C., Schauer, G.F., Gorno-Tempini, M.L., Weiner, M.W., Miller, B.L., Neuroanatomical correlates of behavioural disorders in dementia (2005) Brain, 128, pp. 2612-2625; Zamboni, G., Huey, E.D., Krueger, F., Nichelli, P.F., Grafman, J., Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates (2008) Neurology, 71, pp. 736-742; Ducharme, S., Price, B.H., Dickerson, B.C., Apathy: a neurocircuitry model based on frontotemporal dementia (2018) J Neurol Neurosurg Psychiatry, 89, pp. 389-396; Passamonti, L., Lansdall, C.J., Rowe, J.B., The neuroanatomical and neurochemical basis of apathy and impulsivity in frontotemporal lobar degeneration (2018) Curr Opin Behav Sci, 22, pp. 14-20; Eslinger, P.J., Moore, P., Antani, S., Anderson, C., Grossman, M., Apathy in frontotemporal dementia: behavioral and neuroimaging correlates (2012) Behav Neurol, 25, pp. 127-136; O'Callaghan, C., Hodges, J.R., Hornberger, M., Inhibitory dysfunction in frontotemporal dementia: a review (2013) Alzheimer Dis Assoc Disord., 27, pp. 102-108; Hornberger, M., Piguet, O., Kipps, C., Hodges, J.R., Executive function in progressive and nonprogressive behavioral variant frontotemporal dementia (2008) Neurology, 71, pp. 1481-1488; Stopford, C.L., Thompson, J.C., Neary, D., Richardson, A.M.T., Snowden, J.S., Working memory, attention, and executive function in Alzheimer's disease and frontotemporal dementia (2012) Cortex, 48, pp. 429-446; Staffaroni, A.M., Bajorek, L., Casaletto, K.B., Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint (2020) Alzheimer's Dement, 16, pp. 11-21; Rohrer, J.D., Nicholas, J.M., Cash, D.M., Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis (2015) Lancet Neurol, 14, pp. 253-262; Jiskoot, L.C., Panman, J.L., van, A.L., Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia (2018) J Neurol, 265, pp. 1381-1392. , e al; Jaeger, J., Digit Symbol Substitution Test: the case for sensitivity over specificity in neuropsychological testing (2018) J Clin Psychopharmacol, 38, pp. 513-519; Joy, S., Fein, D., Kaplan, E., Decoding Digit Symbol: speed, memory, and visual scanning (2003) Assessment, 10, pp. 56-65; Baune, B.T., Brignone, M., Larsen, K.G., A network meta-analysis comparing effects of various antidepressant classes on the Digit symbol Substitution Test (DSST) as a measure of cognitive dysfunction in patients with major depressive disorder (2018) Int J Neuropsychopharmacol, 21, pp. 97-107; Knowles, E.E.M., Weiser, M., David, A.S., Glahn, D.C., Davidson, M., Reichenberg, A., The puzzle of processing speed, memory, and executive function impairments in schizophrenia: fitting the pieces together (2015) Biol Psychiatry, 78, pp. 786-793; Marshall, G.A., Rentz, D.M., Frey, M.T., Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease (2011) Alzheimer's Dement, 7, pp. 300-308; Verghese, J., Wang, C., Lipton, R.B., Holtzer, R., Xue, X., Quantitative gait dysfunction and risk of cognitive decline and dementia (2007) J Neurol Neurosurg Psychiatry, 78, pp. 929-935; Tabert, M.H., Manly, J.J., Liu, X., Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment (2006) Arch Gen Psychiatry, 63, pp. 916-924; Rohrer, J.D., Guerreiro, R., Vandrovcova, J., The heritability and genetics of frontotemporal lobar degeneration (2009) Neurology, 73, pp. 1451-1456; Greaves, C.V., Rohrer, J.D., An update on genetic frontotemporal dementia (2019) J Neurol, 266, pp. 2075-2086; Moore, K.M., Nicholas, J., Grossman, M., Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study (2020) Lancet Neurol, 19, pp. 145-156; Matarazzo, J.D., Herman, D.O., Base rate data for the WAIS-R : test-retest stability and VIQ-PIQ differences (1984) J Clin Neuropsychol, 6, pp. 351-366. , https://doi.org/10.1080/01688638408401227; Reuter, M., Schmansky, N.J., Rosas, H.D., Fischl, B., Within-subject template estimation for unbiased longitudinal image analysis (2012) Neuroimage, 61, pp. 1402-1418; Duncan, T.E., Duncan, S.C., The ABC's of LGM: an introductory guide to latent variable growth curve modeling (2009) Soc Personal Psychol Compass, 3, pp. 979-991; Newsom, J.T., (2015) Longitudinal Structural Equation Modeling: A Comprehensive Introduction, , New York, Routledge; Rosseel, Y., lavaan : an R package for structural equation modeling (2012) J Stat Softw, 48 (2), pp. 1-36; Schermelleh-Engel, K., Moosbrugger, H., Müller, H., Evaluating the fit of structural equation models : tests of significance and descriptive goodness-of-fit measures (2003) Methods Psychol Res Online, 8, pp. 23-74; Johnson, E., Kumfor, F., Overcoming apathy in frontotemporal dementia: challenges and future directions (2018) Curr Opin Behav Sci, 22, pp. 82-89; Jiskoot, L.C., Panman, J.L., Meeter, L.H., Longitudinal multimodal MRI as prognostic and diagnostic biomarker in presymptomatic familial frontotemporal dementia (2019) Brain, 142, pp. 193-208; Del Prete, M., Spaccavento, S., Craca, A., Fiore, P., Angelelli, P., Neuropsychiatric symptoms and the APOE genotype in Alzheimer's disease (2009) Neurol Sci, 30, pp. 367-373; Woollacott, I.O.C., Rohrer, J.D., The clinical spectrum of sporadic and familial forms of frontotemporal dementia (2016) J Neurochem, 138, pp. 6-31; Takada, L.T., Sha, S.J., Neuropsychiatric features of C9orf72-associated behavioral variant frontotemporal dementia and frontotemporal dementia with motor neuron disease (2012) Alzheimers Res Ther, 4, p. 38; Le Ber, I., Camuzat, A., Hannequin, D., Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study (2008) Brain, 131, pp. 732-746; Piguet, O., Brooks, W.S., Halliday, G.M., Similar early clinical presentations in familial and non-familial frontotemporal dementia (2004) J Neurol Neurosurg Psychiatry, 75, pp. 1743-1745; Snowden, J.S., Adams, J., Harris, J., Distinct clinical and pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72 mutations (2015) Amyotroph Lateral Scler Frontotemporal Degener, 16, pp. 497-505; Tavares, T.P., Mitchell, D.G.V., Coleman, K.K.L., Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration (2020) J Neurol Neurosurg Psychiatry, 91, pp. 975-984; Levy, R., Dubois, B., Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits (2006) Cereb Cortex, 16, pp. 916-928; Sellami, L., Bocchetta, M., Masellis, M., Distinct neuroanatomical correlates of neuropsychiatric symptoms in the three main forms of genetic frontotemporal dementia in the GENFI cohort (2018) J Alzheimer's Dis, 65, pp. 147-163; Hollocks, M.J., Lawrence, A.J., Brookes, R.L., Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes (2015) Brain, 138, pp. 3803-3815; Starkstein, S.E., Ingram, L., Garau, M.L., Mizrahi, R., On the overlap between apathy and depression in dementia (2005) J Neurol Neurosurg Psychiatry, 76, pp. 1070-1074; Levy, M.L., Cummings, J.L., Fairbanks, L.A., Apathy is not depression (1998) J Neuropsychiatry Clin Neurosci, 10, pp. 314-319; Vicini Chilovi, B., Conti, M., Zanetti, M., Mazzù, I., Rozzini, L., Padovani, A., Differential impact of apathy and depression in the development of dementia in mild cognitive impairment patients (2009) Dement Geriatr Cogn Disord, 27, pp. 390-398; Kirsch-Darrow, L., Fernandez, H.F., Marsiske, M., Okun, M.S., Bowers, D., Dissociating apathy and depression in Parkinson disease (2006) Neurology, 67, pp. 33-38; Rowe, J.B., Parkinsonism in frontotemporal dementias (2019) Int Rev Neurobiol, pp. 249-275. , 149; Padala, P.R., Padala, K.P., Lensing, S.Y., Methylphenidate for apathy in community-dwelling older veterans with mild Alzheimer's disease: a double-blind, randomized, placebo-controlled trial (2018) Am J Psychiatry, 175, pp. 159-168; Ventura, J., Subotnik, K.L., Gretchen-Doorly, D., Cognitive remediation can improve negative symptoms and social functioning in first-episode schizophrenia: a randomized controlled trial (2019) Schizophr Res, 203, pp. 24-31
PY - 2020/12/14
Y1 - 2020/12/14
N2 - Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association
AB - Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association
KW - apathy
KW - cognitive decline
KW - genetic frontotemporal dementia
KW - longitudinal design
KW - MRI
KW - presymptomatic carriers
U2 - 10.1002/alz.12252
DO - 10.1002/alz.12252
M3 - Article
JO - Alzheimer's Dementia
JF - Alzheimer's Dementia
SN - 1552-5260
ER -