Advanced structural brain aging in preclinical autosomal dominant Alzheimer disease

被引：4

作者：

Millar, Peter R. ^{[1
]}

Gordon, Brian A. ^{[2
]}

Wisch, Julie K. ^{[1
]}

Schultz, Stephanie A. ^{[3
,4
]}

Benzinger, Tammie L. S. ^{[2
]}

Cruchaga, Carlos ^{[5
]}

Hassenstab, Jason J. ^{[1
]}

Ibanez, Laura ^{[1
,5
,6
]}

Karch, Celeste ^{[5
]}

Llibre-Guerra, Jorge J. ^{[1
]}

Morris, John C. ^{[1
]}

Perrin, Richard J. ^{[1
,7
]}

Supnet-Bell, Charlene ^{[1
]}

Xiong, Chengjie ^{[8
]}

Allegri, Ricardo F. ^{[9
]}

Berman, Sarah B. ^{[10
]}

Chhatwal, Jasmeer P. ^{[3
,4
]}

Chrem Mendez, Patricio A. ^{[9
]}

Day, Gregory S. ^{[11
]}

Hofmann, Anna ^{[12
,13
]}

Ikeuchi, Takeshi ^{[14
]}

Jucker, Mathias ^{[12
,13
]}

Lee, Jae-Hong ^{[15
]}

Levin, Johannes ^{[16
,17
,18
]}

Lopera, Francisco ^{[19
]}

Niimi, Yoshiki ^{[20
]}

Sanchez-Gonzalez, Victor J. ^{[21
]}

Schofield, Peter R. ^{[22
,23
]}

Sosa-Ortiz, Ana Luisa ^{[24
]}

Voglein, Jonathan ^{[16
,17
]}

Bateman, Randall J. ^{[1
]}

Ances, Beau M. ^{[1
,2
]}

McDade, Eric M. ^{[1
]}

机构：

[1] Washington Univ, Dept Neurol, St Louis, MO 63130 USA

[2] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA

[3] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[5] Washington Univ, Dept Psychiat, St Louis, MO USA

[6] Washington Univ St Louis, NeuroGenom & Informat Ctr, St Louis, MO 63110 USA

[7] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA

[8] Washington Univ, Dept Biostat, St Louis, MO USA

[9] Inst Neurol Fleni, Buenos Aires, DF, Argentina

[10] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA

[11] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[12] German Ctr Neurodegenerat Dis DZNE, D-72076 Tubingen, Germany

[13] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, D-72076 Tubingen, Germany

[14] Niigata Univ, Brain Res Inst, Dept Mol Genet, Niigata, Japan

[15] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea

[16] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[17] German Ctr Neurodegenerat Dis, Munich, Germany

[18] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[19] Univ Antioquia, Medellin, Colombia

[20] Univ Tokyo Hosp, Unit Early & Exploratory Clin Dev, Bunkyo Ku, Tokyo, Japan

[21] Univ Guadalajara, Dept Clin, CUALTOS, Tepatitlan De Morelos, Jalisco, Mexico

[22] Neurosci Res Australia, Sydney, NSW, Australia

[23] Univ New South Wales, Sch Biomed Sci, Sydney, NSW, Australia

[24] Inst Nacl Neurol & Neurocirugia MVS, Mexico City, DF, Mexico

来源：

MOLECULAR NEURODEGENERATION | 2023年 / 18卷 / 01期

关键词：

Brain aging; Alzheimer disease; Structural MRI; Machine learning; AMYLOID ANGIOPATHY; VERBAL MEMORY; DOWN-SYNDROME; AGE; INDIVIDUALS; MRI; ASSOCIATIONS; DEPOSITION; NETWORK; COHORT;

D O I：

10.1186/s13024-023-00688-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background"Brain-predicted age" estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology.MethodsWe modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established markers of amyloid (PiB PET, CSF amyloid-beta-42/40), phosphorylated tau (CSF and plasma pTau-181), neurodegeneration (CSF and plasma neurofilament-light-chain [NfL]), and cognition (global neuropsychological composite and CDR-sum of boxes). We compared BAG to other MRI measures, and examined heterogeneity in BAG as a function of ADAD mutation variants, APOE epsilon 4 carrier status, sex, and education.ResultsAdvanced brain aging was observed in mutation-carriers approximately 7 years before expected symptom onset, in line with other established structural indicators of atrophy. BAG was moderately associated with amyloid PET and strongly associated with pTau-181, NfL, and cognition in mutation-carriers. Mutation variants, sex, and years of education contributed to variability in BAG.ConclusionsWe extend prior work using BAG from sporadic AD to ADAD, noting consistent results. BAG associates well with markers of pTau, neurodegeneration, and cognition, but to a lesser extent, amyloid, in ADAD. BAG may capture similar signal to established MRI measures. However, BAG offers unique benefits in simplicity of data processing and interpretation. Thus, results in this unique ADAD cohort with few age-related confounds suggest that brain aging attributable to AD neuropathology can be accurately quantified from minimally-processed MRI.

引用

页数：17

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