Effect of genetic and vascular AD risk factors on rate of cognitive decline in EOAD vs LOAD

Abstract

AbstractBackground APOE ε4 and vascular factors are well‐known risk factors for developing AD. The effect of these risk factors on rate of cognitive decline in early‐ or late‐onset AD (EOAD and LOAD) is not well understood. We investigated the effect of known AD risk factors (APOE ε4, education, hypertension, diabetes, dyslipidemia, and obesity) on longitudinal cognitive decline in EOAD and LOAD.MethodCognitive and demographic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study was used. We identified 203 EOAD and 1055 LOAD subjects based on age of onset of cognitive decline < or ≥65. Language function was assessed using the Boston Naming Test. Visuospatial function was assessed using ADAS‐Cog constructional praxis. Verbal memory was assessed by summing the scores of word recall (ADAS‐WRT),Delayed Word recall and Word recognition (ADAS‐Word). Executive function was assessed by using the category fluency test. For general cognition we used Mini‐Mental Status Examination (MMSE) and clinical dementia rating sum of boxes (CDR‐SB). To evaluate whether the risk factors had differential effect on the rate of cognitive decline between EOAD and LOAD, we performed univariable analysis for three‐way interaction (risk factor*time*group) and in multivariable analyses, we included age, time, risk factor, group, two‐way interaction effect (risk factor*group, time*group), and three‐way interaction effect (risk factor*time*group) that showed significance in univariable analyses for three‐ways interaction (p<.05).ResultBaseline characteristics and demographic of participants are described in (Table 1). APOE ε4 carrier status was associated with significantly faster decline in language, visuospatial, verbal memory, executive function and MMSE in LOAD (p<0.05). In EOAD it was only associated with faster decline in language domain (p=0.046). LOAD carriers had slower rate of decline in CDR‐SB. Being overweight was associated with a significantly different rate of decline between EOAD and LOAD for visuospatial function (p=0.04) and MMSE(p=0.02). It was also significantly associated with faster decline in CDR‐SB(p=0.03) in EOAD. Obesity was significantly associated with faster decline in CDR‐SB in EOAD (p=0.004) but not LOAD (Table 2).ConclusionKnown risk factors for AD can have differential effect on type of cognitive trajectories based on age of onset of disease.