Role of Impaired Cognitive States & Risk Factors in Conversion to Mixed Dementias

This is a competing renewal of the above mentioned grant which will request funds to secure medical claims data, including medications, from the Centers for Medicare and Medicaid Services for the purpose of determining the severity and duration of self-reported comorbidities, with an emphasis on diabetes and hypertension, in 5,700 participants in the project. Our research has shown a link between these risks and cognitive decline and cerebrovascular pathology but not Alzheimer’s pathology. Also, our research has shown that despite risk factors and the presence of milder forms of cognitive impairment, not all elderly individuals will develop dementia before dying. Medicare claims data will determine the severity of these conditions by revealing associated complications and will allow us to clarify for the first time the role of diabetes and hypertension in cognitive decline as well as mixed dementia pathology. We hypothesize that T2DM and HTN are negatively associated with cerebrovascular health but not AD or other neurodegenerative disease pathologies. However, these associations may be modified by multi-morbidity or treatment. Many key comorbidities, such as renal, respiratory, and autoimmune diseases, have been understudied in the field, and may contribute to cognitive impairment through non-AD pathways. Additionally, we hypothesize that transitions into and out of cognitive states are associated with multi-morbidity. We propose the following Specific Aims: Aim 1. Update and extensively revise the existing SMART project database (n = 5,032; 68% female) with additional participant data, and obtain and integrate linked Medicare claims data. Aim 2. Investigate the relationship of HTN and T2DM in advanced old age with AD and non-AD neuropathologies. Hypothesis: participants with more complicated cases of HTN and/or T2DM (i.e., those with additional comorbidities) have an increased risk of having cerebrovascular and mixed pathologies, but not pure AD pathology, after adjustment for confounding factors. Feasibility: The SMART database has information on over 1,600 autopsies from individuals who die in their ninth decade of life or later; this is expected to grow to at least 2,200 autopsies. Aim 3. Investigate the relationship of HTN and T2DM in advanced old age with cognitive states including subjective memory complaints, mild cognitive impairment, and dementia. Hypothesis: participants with more complicated cases of HTN and/or T2DM (i.e., those with additional comorbidities) will enter pre-dementia states earlier and remain there for shorter intervals before experiencing worse cognition, after adjustment for confounding factors. Feasibility: The SMART project currently has 7.2 ± 4.9 cognitive assessments per participant.