This prospective 5-year study will examine how long-term type 2 diabetes characteristics and inflammation affect the development of cognitive decline in a cohort of 1000 cognitively intact (at recruitment) diabetic individuals 65 years and older living in Tel-Aviv, Israel. This study is a collaboration of the Department of Psychiatry at the Mount Sinai School of Medicine (MSSM), NY, the Department of Psychiatry at the Sheba Medical Center, Israel, and the Department of Community Health of the Maccabi Health Services (MHS), the second largest HMO in Israel. It provides health care to a representative cross section of 1.7 million Israeli citizens, 11,000 of whom have diabetes and are above the age of 65 in the area of Tel-Aviv. The benefits of studying this population are: a) up to 10 years of data from the extraordinarily rich MHS Diabetes Registry, including HbA1c, anti-diabetic and other medication, duration of disease, hypertension and other diabetes related characteristics;b) fully computerized centrally processed MHS medical records, facilitating data access and analysis;c) no charge to patients for analyses by the MHS centralized laboratory, ensuring complete use;d) significantly subsidized medication from MHS pharmacies, which record every purchase (in contrast to subject report of medication prescribed);e) minimal loss to contact since ill subjects are cared for by MHS; and f) prompt death notification by ending of client funding. The dementia diagnostic procedures at Sheba will be fully integrated with those of the MSSM Alzheimer's Disease Research Center (ADRC). Subjects will be followed at 18-month intervals. Diagnostic consensus teleconferences including both Israeli and ADRC physicians will have clinical, neuropsychological, and MRI data collected by this project in addition to complete MHS laboratory and medical data. DNA will be collected and a data sharing plan is in place.
The specific aims are to investigate the impact of baseline 1) inflammation, 2) poor long-term glycemic control, 3) diabetes medication, specifically metformin, and 4) MRI abnormalities, on the rate of cognitive decline. Additionally, the contribution of inflammation or MRI abnormalities to the associations of glycemic control or diabetes medication use with cognitive outcomes will be examined. Beyond investigating the relationship of cognitive decline in diabetes, identifying the impact of inflammation-a modifiable risk factor-within this relationship, has implications for mechanisms underlying incipient dementia in the general population, and could provide the basis for future intervention studies with potential great public health impact. Demonstrating how brain abnormalities link diabetes characteristics to cognitive decline would support a causative or contributive role of these characteristics in cognitive compromise.
This study of diabetic individuals will investigate the roles of inflammation, poor glycemic control, use of diabetes medications, and brain abnormalities at baseline on the rates of cognitive decline. Ultimately, our goal is to extend life without cognitive compromise. This study will point to interventions to assist individuals with diabetes, who are at high risk for dementia. Since rates of diabetes and dementia are disproportionately increasing, especially so as the population structure shifts strongly toward the aged, this study can be expected to have major public health implications. Furthermore, identifying the impact of inflammation and brain abnormalities on risk for cognitive impairment has implications for mechanisms of dementia in the general population, which may lead to even broader based preventive or palliative interventions for cognitive decline and dementia.
|Greenbaum, Lior; Ravona-Springer, Ramit; Lubitz, Irit et al. (2016) Potential contribution of the Alzheimer's disease risk locus BIN1 to episodic memory performance in cognitively normal Type 2 diabetes elderly. Eur Neuropsychopharmacol 26:787-95|
|Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony et al. (2016) Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes. Int J Geriatr Psychiatry 31:494-501|
|Ravona-Springer, Ramit; Haratz, Salo; Tanne, David et al. (2015) Arterial wall function is associated with cognitive performance primarily in elderly with type 2 diabetes. J Alzheimers Dis 44:687-93|
|Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony et al. (2015) Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes. Diabetologia 58:736-44|
|Heymann, Anthony D; Ravona-Springer, Ramit; Moshier, Erin L et al. (2015) Statin Use is Associated with Better Cognitive Function in Elderly with Type 2 Diabetes. J Alzheimers Dis 47:55-9|
|Lunnon, Katie; Smith, Rebecca G; Cooper, Itzik et al. (2015) Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus. Neurobiol Aging 36:1600.e1-4|
|Akrivos, Jimmy; Ravona-Springer, Ramit; Schmeidler, James et al. (2015) Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes. Int J Geriatr Psychiatry 30:1093-100|
|West, Rebecca K; Ravona-Springer, Ramit; Heymann, Anthony et al. (2015) Shorter adult height is associated with poorer cognitive performance in elderly men with type II diabetes. J Alzheimers Dis 44:927-35|
|Greenbaum, Lior; Springer, Ramit Ravona; Lutz, Michael W et al. (2014) The TOMM40 poly-T rs10524523 variant is associated with cognitive performance among non-demented elderly with type 2 diabetes. Eur Neuropsychopharmacol 24:1492-9|
|Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Schmeidler, James et al. (2014) Age, gender, and education are associated with cognitive performance in an older Israeli sample with type 2 diabetes. Int J Geriatr Psychiatry 29:299-309|
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