Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease

被引：9

作者：

Llibre-Guerra, Jorge J. ^{[1
,19
]}

Iaccarino, Leonardo ^{[2
]}

Coble, Dean

Edwards, Lauren ^{[2
]}

Li, Yan ^{[3
]}

Mcdade, Eric ^{[1
]}

Strom, Amelia ^{[2
]}

Gordon, Brian ^{[4
]}

Mundada, Nidhi ^{[2
]}

Schindler, Suzanne E. ^{[1
]}

Tsoy, Elena ^{[2
]}

Ma, Yinjiao ^{[3
]}

Lu, Ruijin ^{[3
]}

Fagan, Anne M. ^{[1
]}

Benzinger, Tammie L. S. ^{[4
]}

Soleimani-Meigooni, David ^{[2
]}

Aschenbrenner, Andrew J. ^{[1
]}

Miller, Zachary ^{[2
]}

Wang, Guoqiao ^{[3
]}

Kramer, Joel H. ^{[2
]}

Hassenstab, Jason ^{[1
]}

Rosen, Howard J. ^{[2
]}

Morris, John C. ^{[1
]}

Miller, Bruce L. ^{[2
]}

Xiong, Chengjie ^{[3
]}

Perrin, Richard J. ^{[1
,5
]}

Allegri, Ricardo ^{[6
]}

Chrem, Patricio ^{[6
]}

Surace, Ezequiel ^{[6
]}

Berman, Sarah B. ^{[7
]}

Chhatwal, Jasmeer ^{[8
]}

Masters, Colin L. ^{[9
]}

Farlow, Martin R. ^{[10
]}

Jucker, Mathias ^{[11
,12
]}

Levin, Johannes ^{[13
,14
,15
]}

Fox, Nick C. ^{[16
]}

Day, Gregory ^{[17
]}

Gorno-Tempini, Maria Luisa ^{[2
]}

Boxer, Adam L. ^{[2
]}

La Joie, Renaud ^{[2
]}

Rabinovici, Gil D. ^{[2
,18
]}

Bateman, Randall ^{[1
]}

机构：

[1] Washington Univ St Louis, Dept Neurol, St Louis, MO 63108 USA

[2] Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA

[3] Washington Univ St Louis, Div Biostat, St Louis, MO 63108 USA

[4] Washington Univ St Louis, Malinckrodt Inst Radiol, St Louis, MO 63108 USA

[5] Washington Univ St Louis, Dept Pathol & Immunol, St Louis, MO 63108 USA

[6] Inst Neurol Res Fleni, Dept Cognit Neurol, Buenos Aires, DF, Argentina

[7] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA

[9] Univ Melbourne, Florey Inst, Melbourne 3052, Australia

[10] Indiana Univ Sch Med, Neurosci Ctr, Indianapolis, IN 46202 USA

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

[12] Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany

[13] Ludwig Maximilians Univ Munchen, Dept Neurol, D-80539 Munich, Germany

[14] German Ctr Neurodegenerat Dis, D-81377 Munich, Germany

[15] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

[16] UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, London WC1N 3BG, England

[17] Mayo Clin Florida, Dept Neurol, Jacksonville, FL 33224 USA

[18] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94158 USA

[19] Washington Univ St Louis, Dept Neurol, 660 S Euclid Ave,Campus Box 8111, St Louis, MO 63108 USA

来源：

BRAIN COMMUNICATIONS | 2023年 / 5卷 / 06期

关键词：

early-onset Alzheimer's disease; sporadic; dominantly inherited; DATA SET UDS; AUTOSOMAL-DOMINANT; AMYLOID DEPOSITION; TAU ACCUMULATION; IN-VIVO; DEMENTIA; PATTERNS; PRESENILIN-1; DIAGNOSIS; ATROPHY;

D O I：

10.1093/braincomms/fcad280

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD +/- 8.5) years versus 54.8 (SD +/- 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-epsilon 4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD +/- 39.3) pg/ml dominantly inherited versus 296 (SD +/- 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design.

引用

页数：15

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