OBJECTIVES: To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene. DESIGN: Clinical histories were obtained by patient and family interviews and through medical or civil records. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 have definitive (autopsy-proven) early-onset AD, 93 have probable early-onset AD, and 29 have possible early-onset AD. SETTING: Community based in Antioquia, Colombia. PATIENTS: A population-based sample in which all members of 5 extended families (nearly 3000 individuals) were surveyed. Criteria for inclusion required obtaining sufficient information to categorize the individual as affected. MAIN OUTCOME MEASURES: Age at onset, neuropsychological profile, neurologic history, and examination. RESULTS: The patients had a mean age at onset of 46.8 years (range, 34-62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentation was memory loss followed by behavior and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. CONCLUSIONS: Other than the early onset, this clinical phenotype is indistinguishable from sporadic AD except that affected individuals frequently complained of headache preceding and during the disease. Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.
OBJECTIVES: To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene. DESIGN: Clinical histories were obtained by patient and family interviews and through medical or civil records. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 have definitive (autopsy-proven) early-onset AD, 93 have probable early-onset AD, and 29 have possible early-onset AD. SETTING: Community based in Antioquia, Colombia. PATIENTS: A population-based sample in which all members of 5 extended families (nearly 3000 individuals) were surveyed. Criteria for inclusion required obtaining sufficient information to categorize the individual as affected. MAIN OUTCOME MEASURES: Age at onset, neuropsychological profile, neurologic history, and examination. RESULTS: The patients had a mean age at onset of 46.8 years (range, 34-62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentation was memory loss followed by behavior and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. CONCLUSIONS: Other than the early onset, this clinical phenotype is indistinguishable from sporadic AD except that affected individuals frequently complained of headache preceding and during the disease. Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.
Authors: Yakeel T Quiroz; Andrew E Budson; Kim Celone; Adriana Ruiz; Randall Newmark; Gabriel Castrillón; Francisco Lopera; Chantal E Stern Journal: Ann Neurol Date: 2010-12 Impact factor: 10.422
Authors: J M Ringman; C Diaz-Olavarrieta; Y Rodriguez; M Chavez; L Fairbanks; F Paz; A Varpetian; H C Maldonado; M A Macias-Islas; J Murrell; B Ghetti; C Kawas Journal: Neurology Date: 2005-08-23 Impact factor: 9.910
Authors: John M Ringman; Karen H Gylys; Luis D Medina; Michelle Fox; Vladimir Kepe; Deborah L Flores; Liana G Apostolova; Jorge R Barrio; Gary Small; Daniel H Silverman; Erin Siu; Stephen Cederbaum; Silva Hecimovic; Martina Malnar; Suma Chakraverty; Alison M Goate; Thomas D Bird; James B Leverenz Journal: Neurosci Lett Date: 2010-11-19 Impact factor: 3.046
Authors: Kenneth S Kosik; Claudia Muñoz; Liliana Lopez; Mary Luz Arcila; Gloria García; Lucía Madrigal; Sonia Moreno; Silvia Ríos Romenets; Hugo Lopez; Madelyn Gutierrez; Jessica B Langbaum; William Cho; Shehnaaz Suliman; Pierre N Tariot; Carole Ho; Eric M Reiman; Francisco Lopera Journal: Neurology Date: 2014-12-03 Impact factor: 9.910
Authors: Yakeel T Quiroz; Aaron P Schultz; Kewei Chen; Hillary D Protas; Michael Brickhouse; Adam S Fleisher; Jessica B Langbaum; Pradeep Thiyyagura; Anne M Fagan; Aarti R Shah; Martha Muniz; Joseph F Arboleda-Velasquez; Claudia Munoz; Gloria Garcia; Natalia Acosta-Baena; Margarita Giraldo; Victoria Tirado; Dora L Ramírez; Pierre N Tariot; Bradford C Dickerson; Reisa A Sperling; Francisco Lopera; Eric M Reiman Journal: JAMA Neurol Date: 2015-08 Impact factor: 18.302
Authors: Napatkamon Ayutyanont; Jessica B S Langbaum; Suzanne B Hendrix; Kewei Chen; Adam S Fleisher; Michel Friesenhahn; Michael Ward; Camilo Aguirre; Natalia Acosta-Baena; Lucìa Madrigal; Claudia Muñoz; Victoria Tirado; Sonia Moreno; Pierre N Tariot; Francisco Lopera; Eric M Reiman Journal: J Clin Psychiatry Date: 2014-06 Impact factor: 4.384