Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment.
Alzheimer’s disease
mild behavioral impairment
mild cognitive impairment
neurodegeneration
neurofilament light
neuropsychiatric symptoms
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
1
7
2020
medline:
4
6
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration. The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology. We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBI- n = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years. Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016). These findings suggest MBI is a clinical proxy of early phase neurodegeneration with putative utility in identifying those at dementia risk. MBI can be used as a case ascertainment approach to capture those at high risk for cognitive decline and dementia, and is an important construct for clinicians dealing with cognitive and neuropsychiatric symptomatology in older adults.
Sections du résumé
BACKGROUND
Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration.
OBJECTIVE
The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology.
METHODS
We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBI- n = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years.
RESULTS
Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016).
CONCLUSION
These findings suggest MBI is a clinical proxy of early phase neurodegeneration with putative utility in identifying those at dementia risk. MBI can be used as a case ascertainment approach to capture those at high risk for cognitive decline and dementia, and is an important construct for clinicians dealing with cognitive and neuropsychiatric symptomatology in older adults.
Identifiants
pubmed: 32597801
pii: JAD200011
doi: 10.3233/JAD-200011
pmc: PMC7504997
doi:
Substances chimiques
Biomarkers
0
Neurofilament Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1027Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : CIHR
Pays : Canada
Références
Am J Geriatr Psychiatry. 2013 Jul;21(7):685-95
pubmed: 23567400
BMJ Open. 2019 Dec 18;9(12):e030379
pubmed: 31857299
Mol Psychiatry. 2020 Oct;25(10):2599-2607
pubmed: 30116029
Neurology. 2019 Jul 16;93(3):e252-e260
pubmed: 31182505
JAMA Netw Open. 2019 Aug 2;2(8):e198964
pubmed: 31397865
Clin Epidemiol. 2019 Mar 04;11:217-228
pubmed: 30881138
Can J Neurol Sci. 2019 Sep;46(5):499-511
pubmed: 31309917
Int Psychogeriatr. 2018 Feb;30(2):221-232
pubmed: 28931446
Int Psychogeriatr. 2018 Feb;30(2):209-219
pubmed: 28560931
Am J Psychiatry. 2014 May;171(5):572-81
pubmed: 24700290
J Neurol. 2020 Jan;267(1):162-167
pubmed: 31595378
Int Psychogeriatr. 2018 Feb;30(2):197-207
pubmed: 28689508
Int Psychogeriatr. 2018 Feb;30(2):171-175
pubmed: 29448970
Int Psychogeriatr. 2019 Feb;31(2):231-239
pubmed: 30017017
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Lancet Neurol. 2012 Dec;11(12):1048-56
pubmed: 23137948
Alzheimers Dement. 2016 Jan;12(1):60-4
pubmed: 26710325
Am J Med Genet B Neuropsychiatr Genet. 2018 Dec;177(8):727-735
pubmed: 30378268
Alzheimers Res Ther. 2018 Jul 28;10(1):71
pubmed: 30055655
Neurology. 2017 Nov 21;89(21):2167-2175
pubmed: 29070659
JAMA Neurol. 2019 Jul 1;76(7):791-799
pubmed: 31009028
Alzheimers Dement. 2016 Feb;12(2):195-202
pubmed: 26096665
J Alzheimers Dis. 2020;74(2):669-677
pubmed: 32083586
Neurology. 2016 Sep 27;87(13):1329-36
pubmed: 27581216
Int Psychogeriatr. 2018 Feb;30(2):233-244
pubmed: 28879833
Neuron. 2016 Jul 20;91(2):494-496
pubmed: 27477021
Neurology. 2019 Aug 20;93(8):e766-e777
pubmed: 31320470
Nat Rev Neurol. 2018 Nov;14(11):639-652
pubmed: 30297701
Neurology. 2015 Feb 10;84(6):617-22
pubmed: 25589671
J Alzheimers Dis. 2018;62(1):227-238
pubmed: 29439333
J Alzheimers Dis. 2017;56(3):929-938
pubmed: 28059789
J Psychiatr Res. 2019 Jun;113:137-140
pubmed: 30953863
Alzheimers Dement (Amst). 2019 Sep 27;11:679-689
pubmed: 31673598
PLoS One. 2013 Sep 20;8(9):e75091
pubmed: 24073237
Alzheimers Dement (N Y). 2018 Oct 15;4:565-574
pubmed: 30386821
Int Psychogeriatr. 2018 Feb;30(2):185-196
pubmed: 28899446
J Alzheimers Dis. 2020;75(1):277-288
pubmed: 32250302
Alzheimers Dement (N Y). 2017 Feb 09;3(1):130-138
pubmed: 29067324
Alzheimers Dement (Amst). 2019 Apr 18;11:333-339
pubmed: 31024987
J Alzheimers Dis. 2018;66(1):83-95
pubmed: 30175974
Alzheimers Dement. 2020 Jan;16(1):192-199
pubmed: 31914223
J Alzheimers Dis. 2019;70(2):505-513
pubmed: 31177229
Int Psychogeriatr. 2018 Feb;30(2):177-184
pubmed: 28416030
Am J Geriatr Psychiatry. 2019 Aug;27(8):823-834
pubmed: 30902566
JAMA Neurol. 2020 Aug 1;77(8):955-965
pubmed: 32391858
Prog Neurobiol. 2017 Apr;151:101-138
pubmed: 27084356
JAMA Neurol. 2017 May 1;74(5):557-566
pubmed: 28346578
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
Int Psychogeriatr. 2020 Jun;32(6):705-717
pubmed: 31526407