Frank J Wolters1, Sven J van der Lee1, Peter J Koudstaal1, Cornelia M van Duijn1, Albert Hofman1, M Kamran Ikram1, Meike W Vernooij1, M Arfan Ikram2. 1. Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, Boston, MA. 2. Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, Boston, MA. m.a.ikram@erasmusmc.nl.
Abstract
OBJECTIVE: To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort. METHODS: From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI. RESULTS: Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61-4.15; ≥80 years: HR 1.01, 95% CI 0.58-1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history. CONCLUSIONS: Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.
OBJECTIVE: To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort. METHODS: From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI. RESULTS: Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61-4.15; ≥80 years: HR 1.01, 95% CI 0.58-1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history. CONCLUSIONS: Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.
Authors: M Arfan Ikram; Guy G O Brusselle; Sarwa Darwish Murad; Cornelia M van Duijn; Oscar H Franco; André Goedegebure; Caroline C W Klaver; Tamar E C Nijsten; Robin P Peeters; Bruno H Stricker; Henning Tiemeier; André G Uitterlinden; Meike W Vernooij; Albert Hofman Journal: Eur J Epidemiol Date: 2017-10-24 Impact factor: 8.082
Authors: Jordan M Jackson; Allison A Bay; Jolie Denise Barter; Liang Ni; William Michael Caudle; Monica C Serra; Whitney Wharton; Madeleine E Hackney Journal: J Alzheimers Dis Rep Date: 2020-08-28
Authors: Bessie C Stamm; Patrick J Lao; Batool Rizvi; Juliet Colon; Kay Igwe; Anthony G Chesebro; Benjamin Maas; Nicole Schupf; Richard Mayeux; Jennifer J Manly; Adam M Brickman Journal: J Gerontol A Biol Sci Med Sci Date: 2020-10-15 Impact factor: 6.053
Authors: M Arfan Ikram; Guy Brusselle; Mohsen Ghanbari; André Goedegebure; M Kamran Ikram; Maryam Kavousi; Brenda C T Kieboom; Caroline C W Klaver; Robert J de Knegt; Annemarie I Luik; Tamar E C Nijsten; Robin P Peeters; Frank J A van Rooij; Bruno H Stricker; André G Uitterlinden; Meike W Vernooij; Trudy Voortman Journal: Eur J Epidemiol Date: 2020-05-04 Impact factor: 8.082
Authors: Joyce Vrijsen; Ameen Abu-Hanna; Els Lm Maeckelberghe; Peter Paul De Deyn; Andrea F de Winter; Fransje E Reesink; Richard C Oude Voshaar; Erik Buskens; Sophia E de Rooij; Nynke Smidt Journal: BMJ Open Date: 2020-10-16 Impact factor: 2.692