CONTEXT: The role of genetic factors in Alzheimer disease (AD) varies across the late life span, complicating efforts to quantify the risk of AD for relatives of probands with AD. OBJECTIVES: To visualize the changing levels of familial risk according to proband onset age and the age of the at-risk relative and to determine the familiality of age at onset in AD. DESIGN: A retrospective, informant-based family study. SETTING, PATIENTS, AND OTHER PARTICIPANTS: Siblings and parents of probands with AD (relatives = 4687; probands = 904), ascertained at geriatric clinic and nursing home settings, and of elderly probands without dementia (relatives = 7649; probands = 1525) who were spouses of probands, participants at senior centers, or nursing home residents without dementia. MAIN OUTCOME MEASURES: Informant-based assessments of AD in the relatives were used to generate 3-dimensional surfaces representing the patterns of risk of AD across the late life span depending on the specific onset age of the proband with AD (or assessment age of the elderly proband without dementia). We then constructed a 3-dimensional, age-specific, 10-year hazard rate ratio (HRR) surface representing the relative risk of AD in relatives of probands with AD with smoothly shifting levels of onset age compared with relatives of elderly probands without dementia. RESULTS: The HRR surface peaked (HRR, 13.0) for younger sexagenarian relatives related to probands with AD with onset age in their early 60s. The HRRs dropped sharply both as the proband age at onset and the age of the relative increased. For relatives aged in their late 80s, the HRR fell lower than 2.0 regardless of proband onset age and their lower-limit 95% confidence intervals were less than 1.0. CONCLUSIONS: The role of genetic risk factors decreases with increasing onset age of the proband with AD regardless of the age of the relatives themselves. The familiality of onset age is greatly reduced at later ages. The role of environmental risk factors in AD likely increases with onset age.
CONTEXT: The role of genetic factors in Alzheimer disease (AD) varies across the late life span, complicating efforts to quantify the risk of AD for relatives of probands with AD. OBJECTIVES: To visualize the changing levels of familial risk according to proband onset age and the age of the at-risk relative and to determine the familiality of age at onset in AD. DESIGN: A retrospective, informant-based family study. SETTING, PATIENTS, AND OTHER PARTICIPANTS: Siblings and parents of probands with AD (relatives = 4687; probands = 904), ascertained at geriatric clinic and nursing home settings, and of elderly probands without dementia (relatives = 7649; probands = 1525) who were spouses of probands, participants at senior centers, or nursing home residents without dementia. MAIN OUTCOME MEASURES: Informant-based assessments of AD in the relatives were used to generate 3-dimensional surfaces representing the patterns of risk of AD across the late life span depending on the specific onset age of the proband with AD (or assessment age of the elderly proband without dementia). We then constructed a 3-dimensional, age-specific, 10-year hazard rate ratio (HRR) surface representing the relative risk of AD in relatives of probands with AD with smoothly shifting levels of onset age compared with relatives of elderly probands without dementia. RESULTS: The HRR surface peaked (HRR, 13.0) for younger sexagenarian relatives related to probands with AD with onset age in their early 60s. The HRRs dropped sharply both as the proband age at onset and the age of the relative increased. For relatives aged in their late 80s, the HRR fell lower than 2.0 regardless of proband onset age and their lower-limit 95% confidence intervals were less than 1.0. CONCLUSIONS: The role of genetic risk factors decreases with increasing onset age of the proband with AD regardless of the age of the relatives themselves. The familiality of onset age is greatly reduced at later ages. The role of environmental risk factors in AD likely increases with onset age.
Authors: Lisa Mosconi; Wai Tsui; John Murray; Pauline McHugh; Yi Li; Schantel Williams; Elizabeth Pirraglia; Lidia Glodzik; Susan De Santi; Shankar Vallabhajosula; Mony J de Leon Journal: Neurobiol Aging Date: 2011-04-22 Impact factor: 4.673
Authors: Lisa Mosconi; Juha O Rinne; Wai H Tsui; Valentina Berti; Yi Li; Huiyu Wang; John Murray; Noora Scheinin; Kjell Någren; Schantel Williams; Lidia Glodzik; Susan De Santi; Shankar Vallabhajosula; Mony J de Leon Journal: Proc Natl Acad Sci U S A Date: 2010-03-15 Impact factor: 11.205
Authors: Jeremy M Silverman; Michal Schnaider Beeri; James Schmeidler; Clive Rosendorff; Gary Angelo; Rizalina S Mavris; Hillel T Grossman; Gregory A Elder; Jose Carrion-Baralt; Rebecca West Journal: Age Ageing Date: 2009-01-15 Impact factor: 10.668
Authors: Valentina Berti; Lisa Mosconi; Lidia Glodzik; Yi Li; John Murray; Susan De Santi; Alberto Pupi; Wai Tsui; Mony J De Leon Journal: Neurobiol Aging Date: 2011-02-12 Impact factor: 4.673
Authors: Lisa Mosconi; John Murray; Wai H Tsui; Yi Li; Nicole Spector; Alexander Goldowsky; Schantel Williams; Ricardo Osorio; Pauline McHugh; Lidia Glodzik; Shankar Vallabhajosula; Mony J de Leon Journal: Neurology Date: 2014-02-12 Impact factor: 9.910
Authors: Alessandra Pani; Antonella Mandas; Giacomo Diaz; Claudia Abete; Pier Luigi Cocco; Fabrizio Angius; Annalisa Brundu; Nico Muçaka; Maria Elena Pais; Antonio Saba; Luigi Barberini; Cristina Zaru; Manuela Palmas; Paolo F Putzu; Alessandra Mocali; Francesco Paoletti; Paolo La Colla; Sandra Dessì Journal: BMC Med Date: 2009-11-02 Impact factor: 8.775
Authors: Rachel Mistur; Lisa Mosconi; Susan De Santi; Marla Guzman; Yi Li; Wai Tsui; Mony J de Leon Journal: J Clin Neurol Date: 2009-12-31 Impact factor: 3.077