Document text
Principal Investigator: Katherine Bangen
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $50,054
Funding agency: National Institute on Aging
Type 2 diabetes mellitus (T2DM), which is rising in prevalence, increases risk of cognitive impairment and
dementia, including Alzheimer's disease (AD). In our prior work we have shown that T2DM is associated with
steeper cognitive decline and reduced cerebral blood flow (CBF) in regions that are predilection sites for AD
pathology (Bangen et al., 2018; Bangen et al., in prep). Identifying individuals who are most likely to decline
prior to the occurrence of significant brain changes is essential so that interventions can be applied before
extensive cerebrovascular lesions and cognitive changes develop. Studies investigating incipient cognitive and
brain changes prior to the development of dementia are critical to optimize brain health and improve outcomes.
Most previous neuroimaging studies of brain changes underlying cognitive dysfunction in T2DM have
applied conventional structural magnetic resonance imaging (MRI) to detect end-stage macrostructural
changes associated with cerebrovascular disease (CVD) such as white matter lesions (WML). However, recent
advances in MRI have allowed for the development of sensitive methods for the non-invasive measurement of
CBF and cerebral arterial compliance (AC), or the ability of vessels to distend or increase in volume in
response to changes in blood pressure. Such methods may help elucidate mechanisms that precede the
development of irreversible parenchymal/structural damage and may yield important markers of risk for
cognitive decline. Although T2DM has been associated with peripheral arterial stiffening using carotid-femoral
pulse wave velocity, no studies have examined intracranial arterial stiffening (i.e., decreased AC) in T2DM.
We therefore propose to advance the field by longitudinally assessing neuropsychological functioning, AC
and CBF, and established MRI markers CVD in a sample of 150 older adults (aged 65-85) including 100 with
T2DM and 50 non-diabetic control participants. Participants will undergo comprehensive neuropsychological
assessment; laboratory testing to assess blood-based markers related to glycemia and cardiometabolic health;
and neuroimaging exams including high resolution structural imaging and novel arterial spin labeling (ASL)
MRI protocols that estimate cerebral arterial compliance and blood flow at baseline, 12-month follow up, and
24-month follow up. Our goals are to investigate whether early changes in cerebrovascular functioning (i.e.,
reduced AC and CBF) relate to MRI markers of CVD lesions and cognition in T2DM. We will also investigate
whether diabetes related factors (e.g., duration, glycemic control) and comorbid cardiometabolic conditions
(e.g., hypertension) moderate associations between AC, CBF, CVD markers, and cognition. Findings will help
address an important public health need by identifying markers of cognitive decline in T2DM and elucidating
potentially modifiable mechanisms underlying these changes. Results may also assist in facilitating targeted
interventions given that presence of cognitive dysfunction may affect both dosing and broader management of
individuals with T2DM.
Terms: <AD dementia><AD pathology><Active Follow-up><Address><Adult-Onset Diabetes Mellitus><Affect><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's disease pathology><Alzheimer's pathology><Alzheimers Dementia><Amentia><Apo-E><ApoE><ApoE protein><Apolipoprotein E><Arteriosclerotic Dementia><Autopsy><Bleeding><Blood Pressure><Blood Vessels><Blood flow><Brain><Brain Nervous System><Brain Vascular><Brain Vascular Disorders><Cerebrovascular Circulation><Cerebrovascular Disease><Cerebrovascular Disorders><Cerebrum><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Control Groups><Dementia><Development><Diabetes Mellitus><Diagnosis><Disease Marker><Disturbance in cognition><Dose><Early identification><Encephalon><Family member><Femur><Glycohemoglobin A><Glycosylated hemoglobin A><Goals><Hb A1><Hb A1a+b><Hb A1c><HbA1><HbA1c><Health><Hemoglobin A(1)><Hemorrhage><Hypertension><Impaired cognition><Individual><Intervention><Intervention Strategies><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Ketosis-Resistant Diabetes Mellitus><Laboratories><Lesion><Link><MR Imaging><MR Tomography><MRI><MRI biomarker><MRI marker><MRIs><Magnetic Resonance Imaging><Maturity-Onset Diabetes Mellitus><Measurement><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Methods><NIDDM><NMR Imaging><NMR Tomography><Neuropsychologies><Neuropsychology><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nuclear Magnetic Resonance Imaging><Participant><Peripheral><Physiologic pulse><Prevalence><Primary Senile Degenerative Dementia><Prognosis><Protocol><Protocols documentation><Public Health><Pulse><Resolution><Risk><Risk Factors><Risk Marker><Role><Sampling><Site><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><T2 DM><T2D><T2DM><Technology><Testing><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Vascular Dementia><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><White Matter Hyperintensity><Work><Zeugmatography><active followup><adult onset diabetes><aged><arterial spin labeling><arterial spin tagging><arterial stiffening><arterial stiffness><artery stiffening><artery stiffness><biomarker identification><blood flow in brain><blood loss><blood-based biomarker><blood-based marker><brain blood circulation><brain blood flow><brain health><brain vascular disease><brain vascular dysfunction><cardiometabolic><cardiometabolism><care providers><cerebral><cerebral blood flow><cerebral circulation><cerebral microbleeds><cerebral microhemorrhage><cerebral vascular><cerebral vascular disease><cerebral vascular dysfunction><cerebro-vascular><cerebrocirculation><cerebrovascular><cerebrovascular blood flow><cerebrovascular dysfunction><cerebrovascular lesion><clinical decision-making><co-morbid><co-morbidity><cognitive assessment><cognitive change><cognitive dysfunction><cognitive loss><cognitive testing><comorbidity><customized therapy><customized treatment><dementia risk><demographics><developmental><diabetes><diabetes pathogenesis><early biomarkers><early detection biomarkers><early detection markers><executive control><executive function><follow up><follow-up><followed up><followup><glycemic control><hemoglobin A1c><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><identification of biomarkers><identification of new biomarkers><improved><improved outcome><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><interest><interventional strategy><intracranial vascular dysfunction><ketosis resistant diabetes><magnetic resonance imaging biomarker><magnetic resonance imaging marker><marker identification><maturity onset diabetes><mild cognitive disorder><mild cognitive impairment><necropsy><neural imaging><neuro-imaging><neuroimaging><neurological imaging><neuropathologic><neuropathological><neuropathology><neuropsychologic><non-diabetic><nondiabetic><novel><older adult><older adulthood><patient specific therapies><patient specific treatment><postmortem><primary degenerative dementia><resolutions><response><risk factor for dementia><risk for dementia><risk predictor><risk predictors><senile dementia of the Alzheimer type><social role><structural imaging><substantia alba><tailored medical treatment><tailored therapy><tailored treatment><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><treatment planning><type 2 DM><type II DM><type two diabetes><unique treatment><vascular><vascular contributions to dementia><vascular risk factor><white matter>