Ramit Ravona-Springer1,2,3, Inbal Sharvit-Ginon1, Ithamar Ganmore1,2,3,4, Lior Greenbaum1,3,5, Barbara B Bendlin6, Shelley A Sternberg7, Abigail Livny1,3,8, Liran Domachevsky3,8, Israel Sandler8, Simona Ben Haim9,10, Sapir Golan1, Liat Ben-Ami1,8, Orit Lesman-Segev8, Sigalit Manzali1,11, Anthony Heymann3,7, Michal Schnaider Beeri1,12. 1. The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel. 2. Memory Clinic, Sheba Medical Center, Tel Hashomer, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel. 5. The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel. 6. Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. 7. Maccabi Healthcare Services, Israel. 8. Department of Diagnostic imaging, Seba Medical Center, Tel Hashomer, Israel. 9. Department of Medical Biophysics and Nuclear Medicine, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel. 10. Institute of Nuclear Medicine, University College London and UCL Hospitals, NHS Trust, London, UK. 11. Department of Pathology, Sheba Medical Center, Tel-Hashomer, Israel. 12. Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: Family history of Alzheimer's disease (AD) is associated with increased dementia-risk. OBJECTIVE: The Israel Registry for Alzheimer's Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH-) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. METHODS: Participants are members of the Maccabi Health Services, 40-65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. RESULTS: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH-. Compared to FH-, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele carriers (32.9% FH+, 22% FH-; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH-in global cognition (p = 0.027) and episodic memory (p = 0.022). CONCLUSION: Lower cognitive scores and higher rates of the APOE E4 allele carriers among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.
BACKGROUND: Family history of Alzheimer's disease (AD) is associated with increased dementia-risk. OBJECTIVE: The Israel Registry for Alzheimer's Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of ADpatients (family history positive; FH+) and controls (whose parents have aged without dementia; FH-) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. METHODS:Participants are members of the Maccabi Health Services, 40-65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. RESULTS: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH-. Compared to FH-, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele carriers (32.9% FH+, 22% FH-; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH-in global cognition (p = 0.027) and episodic memory (p = 0.022). CONCLUSION: Lower cognitive scores and higher rates of the APOE E4 allele carriers among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.
Entities:
Keywords:
APOE E4; Alzheimer’s disease; family history; offspring; risk factors