This is a resubmission of a proposal to investigate the relationships among sleep disordered breathing, APOE genotype and cognition. Sleep disordered breathing increases with age and is associated with impaired cognition. The APOE e4 allele has recently been associated with sleep disordered breathing, particularly Obstructive Sleep Apnea Syndrome (OSAS). The e4 allele is an established risk factor for cognitive decline and the development of dementia. This raises an important issue: is the negative impact of APOE e4 allele on cognition and risk for dementia risk due to OSAS? Specifically, in a population already susceptible to accelerated cognitive decline, how do APOE e4 genotype status, presence or development of OSAS and the combination of APOE e4 status and OSAS further accelerate cognitive decline? We are aware of no studies which have directly examined these issues. To address this knowledge gap effectively requires longitudinal collection of data and analytic techniques designed specifically to identify """"""""moderators"""""""" and """"""""mediators"""""""" of cognitive decline. We propose to investigate this issue in a group of 150 older adults, 60 years of age and older who will be followed longitudinally for 4 years. Assessments of cognitive function and OSAS will be conducted at baseline and annually, with APOE status determined at baseline. The following hypotheses will be tested. Hypothesis 1: In older adults, 3 risk factors, sleep disordered breathing, APOE e4 genotype and age and their interactions will predict rate of decline in performance on measures of cognition. Hypothesis 2: APOE e4 moderates the effect of sleep disordered breathing on cognitive decline. Hypothesis 3: Sleep disordered breathing will mediate any negative impact of APOE e4 on cognitive decline. There are currently no effective treatments for cognitive decline or MCI, but there are effective treatments for OSAS. Reducing cognitive impairment and delaying the onset of AD has significant clinical and economic benefits. Thus, the answer to this question could significantly enhance our therapeutic approach to cognitive impairment in older adults.
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