The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease

被引:41
|
作者
Tosto, Giuseppe [1 ,2 ,3 ]
Bird, Thomas D. [4 ,5 ]
Bennett, David A. [6 ]
Boeve, Bradley F. [7 ]
Brickman, Adam M. [1 ,2 ,3 ]
Cruchaga, Carlos [8 ]
Faber, Kelley [9 ]
Foroud, Tatiana M. [9 ]
Farlow, Martin [10 ]
Goate, Alison M. [11 ]
Graff-Radford, Neill R. [12 ]
Lantigua, Rafael [13 ]
Manly, Jennifer [1 ,2 ,3 ]
Ottman, Ruth [1 ,14 ]
Rosenberg, Roger [15 ,16 ]
Schaid, Daniel J. [17 ]
Schupf, Nicole [1 ,2 ,3 ,14 ]
Stern, Yaakov [1 ,2 ,3 ]
Sweet, Robert A. [18 ,19 ,20 ]
Mayeux, Richard [1 ,2 ,3 ,14 ]
机构
[1] Columbia Univ, Coll Phys & Surg, Aging Brain & Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis, 630 W 168th St,Bldg P&S,Box 16, New York, NY 10032 USA
[2] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA
[3] New York Presbyterian Hosp New York City, New York, NY USA
[4] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
[5] Univ Washington, Dept Med, Seattle, WA USA
[6] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA
[7] Mayo Clin, Dept Neurol, Rochester, MI USA
[8] Washington Univ, Hope Ctr Neurol Disorders, St Louis, MO USA
[9] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46204 USA
[10] Indiana Univ, Dept Neurol, Ctr Alzheimers Dis & Related Disorders, Indianapolis, IN 46204 USA
[11] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA
[12] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA
[13] Columbia Univ, Dept Med, New York, NY USA
[14] Columbia Univ, Dept Epidemiol, New York, NY USA
[15] Univ Texas Southwestern Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA
[16] Mayo Clin, JAMA Neurol, Rochester, MN USA
[17] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA
[18] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA
[19] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA
[20] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA
关键词
CEREBROVASCULAR-DISEASE; COGNITIVE IMPAIRMENT; DIABETES-MELLITUS; BLOOD-PRESSURE; REDUCED RISK; DEMENTIA; PATHOLOGY; INDIVIDUALS; STRATEGIES; BLOCKERS;
D O I
10.1001/jamaneurol.2016.2539
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
IMPORTANCE The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. OBJECTIVE To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. DESIGN, SETTING, AND PARTICIPANTS The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights-Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. MAIN OUTCOMES AND MEASURES Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) epsilon 4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE e4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. RESULTS A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated with decreased LOAD risk (odds ratio [OR], 0.63; 95% CI, 0.55-0.72); type 2 diabetes and heart disease were not. History of stroke conferred greater than 2-fold increased risk for LOAD (OR, 2.23; 95% CI, 1.75-2.83). Adjustment for APOE e4 did not alter results. The genetic risk score was associated with LOAD (OR, 2.85; 95% CI, 2.05-3.97) but did not change the independent association of LOAD with hypertension or stroke. In the WHICAP sample, hypertension was not associated with LOAD (OR, 0.99; 95% CI, 0.88-1.11), whereas history of stroke increased the risk for LOAD (OR, 1.96; 95% CI, 1.56-2.46). The effect of hypertension on LOAD risk was also mediated by stroke in the NIA-LOAD and the WHICAP samples. CONCLUSIONS AND RELEVANCE In familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background.
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收藏
页码:1231 / 1237
页数:7
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