TY - JOUR
T1 - Impact of amyloid and cardiometabolic risk factors on prognostic capacity of plasma neurofilament light chain for neurodegeneration
AU - for the Alzheimer's Disease Neuroimaging Initiative
AU - Kim, Keun You
AU - Kim, Eosu
AU - Lee, Jun Young
AU - Raj, Balebail Ashok
AU - Fargher, Kristin
AU - Smith, Amanda
AU - Raudin, Lisa
AU - Chaing, Gloria
AU - Relkin, Norman
AU - Smith, Karen Elizabeth
AU - Shim, Hyungsub
AU - Ponto, Laura L.Boles
AU - Schultz, Susan K.
AU - Sarrael, Antero
AU - Hernando, Raymundo
AU - Pomara, Nunzio
AU - Drost, Dick
AU - Kertesz, Andrew
AU - Rogers, John
AU - Rachinsky, Irina
AU - Pasternak, Stephen
AU - Finger, Elizabether
AU - Bachman, David
AU - Spicer, Kenneth
AU - Mintzer, Jacobo
AU - Miller, Bruce L.
AU - Rosen, Howard J.
AU - Correia, Stephen
AU - Malloy, Paul
AU - Salloway, Stephen
AU - Tremont, Geoffrey
AU - Querfurth, Henry
AU - Ott, Brian R.
AU - Watkins, Franklin
AU - Garg, Pradeep
AU - Williamson, Jeff D.
AU - Sink, Kaycee M.
AU - Schwartz, Eben S.
AU - Kitzmiller, Tamar J.
AU - Santulli, Robert B.
AU - Anderson, Karen
AU - Blank, Karen
AU - Pearlson, Godfrey D.
AU - Brown, Alice D.
AU - Celmins, Dzintra
AU - Zimmerman, Earl A.
AU - Adeli, Anahita
AU - Kataki, Maria
AU - Scharre, Douglas W.
AU - Rainka, Michelle
AU - Capote, Horacio
AU - Bates, Vernice
AU - Reeder, Stephanie
AU - Fleisher, Adam
AU - Tariot, Pierre
AU - Nguyen, Dana
AU - Preda, Adrian
AU - Potkin, Steven G.
AU - Carlsson, Cynthia M.
AU - Asthana, Sanjay
AU - Johnson, Sterling
AU - Bartha, Rob
AU - Lee, T. Y.
AU - Borrie, Michael
AU - Kittur, Smita
AU - DeCarli, Charles
AU - Olichney, John
AU - Carmichael, Owen
AU - Fletcher, Evan
AU - Hudson, Leon
AU - Ogrocki, Paula
AU - Lerner, Alan
AU - Allard, Joanne
AU - Wolday, Saba
AU - Obisesan, Thomas O.
AU - Johnson, Patricia Lynn
AU - Norbash, Alexander
AU - Budson, Andrew E.
AU - Killiany, Ronald
AU - Kowall, Neil
AU - Sirrel, Sherye A.
AU - Jacobson, Sandra A.
AU - Belden, Christine M.
AU - Sabbagh, Marwan N.
AU - Tinklenberg, Jared
AU - Rosen, Allyson
AU - Lane, Barton
AU - Taylor, Joy L.
AU - Yesavage, Jerome
AU - Frey, Meghan
AU - Marshall, Gad
AU - Johnson, Keith A.
AU - Sperling, Reisa A.
AU - Reynolds, Brigid
AU - Johnson, Kathleen
AU - Turner, Raymond Scott
AU - Villena, Teresa
AU - Martinez, Walter
AU - Sadowsky, Carl
AU - Johnson, Nancy
AU - Wu, Chuang Kuo
AU - Lipowski, Kristine
AU - Mesulam, Marek Marsel
AU - Kerwin, Diana
AU - Munic, Donna
AU - Bernick, Charles
AU - Trost, Dick
AU - Rogers, John
AU - Kertesz, Andrew
AU - Assaly, Michele
AU - Mudge, Benita
AU - Feldman, Howard
AU - Hsiung, Ging Yuek Robin
AU - Caldwell, Curtis
AU - Stefanovic, Bojana
AU - Black, Sandra
AU - Hosein, Chris
AU - Bergman, Howard
AU - Chertkow, Howard
AU - MacAvoy, Martha G.
AU - Carson, Richard E.
AU - van Dyck, Christopher H.
AU - Hunt, Cynthia
AU - Herring, Scott
AU - Matthews, Brandy R.
AU - Hake, Ann Marie
AU - Farlow, Martin R.
AU - Johnson, Heather
AU - Kendall, Tracy
AU - Parfitt, Francine
AU - Graff Radford, Neill R.
AU - Bartzokis, George
AU - Lu, Po H.
AU - Silverman, Daniel H.S.
AU - Woo, Ellen
AU - Tingus, Kathleen
AU - Apostolova, Liana
AU - Swerdlow, Russell H.
AU - Anderson, Heather S.
AU - Burns, Jeffrey M.
AU - Cellar, Janet S.
AU - Lah, James J.
AU - Levey, Allan I.
AU - DeVous, Michael
AU - Cook, Kristen Martin
AU - Weiner, Myron
AU - King, Richard
AU - Arrastia, Ramon Diaz
AU - Quiceno, Mary
AU - Mathews, Dana
AU - Womack, Kyle
AU - Mc Adams Ortiz, Catherine
AU - Thai, Gaby
AU - Mulnard, Ruth A.
AU - Brand, Connie
AU - Ismail, M. Saleem
AU - Makino, Kelly M.
AU - Martin, Kim
AU - Goldstein, Bonnie S.
AU - Porsteinsson, Anton P.
AU - Simpson, Donna M.
AU - Oakley, Mary Ann
AU - Lopez, Oscar L.
AU - Conrad, Gary
AU - Oates, Elizabeth
AU - Sinha, Partha
AU - Hardy, Peter
AU - Jicha, Greg
AU - Smith, Charles D.
AU - Wolk, David
AU - Karlawish, Jason H.
AU - Arnold, Steven E.
AU - Wong, Terence Z.
AU - Petrella, Jeffrey R.
AU - Doraiswamy, P. Murali
AU - De Santi, Susan
AU - Glodzik, Lidia
AU - de Leon, Mony J.
AU - Rusinek, Henry
AU - Michel, Christina A.
AU - Cerbone, Brittany
AU - Pogorelec, Dana M.
AU - Galvin, James E.
AU - Kielb, Stephanie
AU - D’Agostino, Daniel
AU - Onyike, Chiadi
AU - Albert, Marilyn
AU - Roberts, Peggy
AU - Greig, Maria T.
AU - Varon, Daniel
AU - Duara, Ranjan
AU - Shah, Raj C.
AU - de Toledo-Morrell, Leyla
AU - Mitsis, Effie
AU - Grossman, Hillel
AU - Roberson, Erik
AU - Brockington, John
AU - Geldmacher, David
AU - Clark, David
AU - Ances, Beau
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Background: Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer’s Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods: Non-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity. Results: Over a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values < 0.001). Notably, Aβ at baseline significantly enhanced the association between plasma NfL and longitudinal changes in ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004). Regarding ADAS-Cog score and WMH volume, the impact of Aβ was more prominent in cognitively unimpaired than in mild cognitive impairment. Hypertension significantly heightened the association between plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, and WMH volumes (all p-values < 0.001). DM influenced the association between plasma NfL and changes in ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. Impaired kidney function did not significantly alter the association between plasma NfL and longitudinal changes in any outcome variables. Obesity heightened the association between plasma NfL and changes in hippocampal volumes only (p-value 0.026). Conclusion: This study suggests that the prognostic capacity of plasma NfL may be amplified in individuals with Aβ or hypertension. This finding emphasizes the importance of considering these factors in the NfL-based prognostic model for neurodegeneration in non-demented older adults.
AB - Background: Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer’s Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods: Non-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity. Results: Over a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values < 0.001). Notably, Aβ at baseline significantly enhanced the association between plasma NfL and longitudinal changes in ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004). Regarding ADAS-Cog score and WMH volume, the impact of Aβ was more prominent in cognitively unimpaired than in mild cognitive impairment. Hypertension significantly heightened the association between plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, and WMH volumes (all p-values < 0.001). DM influenced the association between plasma NfL and changes in ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. Impaired kidney function did not significantly alter the association between plasma NfL and longitudinal changes in any outcome variables. Obesity heightened the association between plasma NfL and changes in hippocampal volumes only (p-value 0.026). Conclusion: This study suggests that the prognostic capacity of plasma NfL may be amplified in individuals with Aβ or hypertension. This finding emphasizes the importance of considering these factors in the NfL-based prognostic model for neurodegeneration in non-demented older adults.
KW - Alzheimer’s disease
KW - Blood-based biomarker
KW - Cardiovascular disease
KW - Dementia
KW - Kidney disease
KW - Metabolic syndrome
KW - Neurofilament light chain
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85203845208&partnerID=8YFLogxK
U2 - 10.1186/s13195-024-01564-y
DO - 10.1186/s13195-024-01564-y
M3 - Article
C2 - 39267169
AN - SCOPUS:85203845208
SN - 1758-9193
VL - 16
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 202
ER -