THE IMPACT OF NORMATIVE AGING AND ALZHEIMERS DISEASE ON FEAR BASED DISORDERS AND AMYGDALA DYSFUNCTION - NOT…
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ASST_NON_R00AG078400_075 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_R00AG078400_075
- FAIN
- R00AG078400
- Recipient
- UNIVERSITY OF ALABAMA AT BIRMINGHAM
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $761,567
- Period
- Aug 1, 2023 – Jul 31, 2026
- Fiscal year
- 2023
- Place of performance state
- AL
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
THE IMPACT OF NORMATIVE AGING AND ALZHEIMERS DISEASE ON FEAR BASED DISORDERS AND AMYGDALA DYSFUNCTION - NOT ONLY DO FEAR-BASED DISORDERS SUCH AS POSTTRAUMATIC STRESS DISORDER (PTSD) QUINTUPLE THE RATE OF SUICIDE RELATIVE TO THOSE WITHOUT THESE DISORDERS, BUT THEY ALSO INCREASE THE MAGNITUDE OF AGE-RELATED COGNITIVE DECLINE AND DOUBLE THE RISK FOR DEVELOPING ALZHEIMERâS DISEASE AND OTHER DEMENTIAS IN OLDER ADULTS. FEAR-BASED DISORDERS LIKE PTSD ARE LINKED TO FEAR MEMORIES. DUE TO THE SEEMINGLY INDELIBLE AND HYPERACTIVE PROPERTIES OF SUCH FEAR MEMORIES, FEAR-BASED DISORDERS CAN WORSEN WITH AGE. ALTHOUGH NORMATIVE AGING AND ALZHEIMERâS DISEASE HAVE DISSOCIABLE TRAJECTORIES, ONE FACTOR THAT NEGATIVELY IMPACTS COGNITIVE AGING AND ALZHEIMERâS DISEASE IS THE COMORBIDITY OF PTSD. PERTURBATIONS IN THE FUNCTIONAL CIRCUITRY SUPPORTING FEAR MEMORY EXTINCTION ARE ALSO KEY NEURAL MECHANISMS OF PTSD. A CRITICAL ANATOMICAL STRUCTURE WITHIN THE NEURAL CIRCUITRY UNDERLYING THIS DYSFUNCTIONAL PROCESSING IS THE BASOLATERAL AMYGDALA (BLA), WHICH IS CONSIDERED AN INTEGRATIVE HUB AS IT RECEIVES SENSORY AND CONTEXTUAL INFORMATION FROM THE PREFRONTAL CORTEX AND HIPPOCAMPUS. WHILE MUCH OF THE CURRENT SCIENTIFIC FOCUS ON COGNITIVE AGING AND ALZHEIMERâS DISEASE CENTERS ON THE PREFRONTAL CORTEX AND HIPPOCAMPUS, LITTLE IS KNOWN ABOUT THE UNDERLYING MECHANISMS OF BLA DYSFUNCTION IN AGING, ALZHEIMERâS DISEASE (AD), AND THE IMPACT OF CO-OCCURRING PTSD. ONE PATHOLOGICAL PROCESS COMMON TO THESE DISORDERS IS UNDERLYING NEUROINFLAMMATION. IMPORTANTLY, KETOGENIC AND KETONE ESTER DIETS ARE KNOWN TO AMELIORATE HYPERACTIVITY, INFLAMMATION, FEAR-BASED DISORDERS, AND SHOW PROMISE AS TREATMENTS FOR THE CONTRIBUTING FACTORS TO COGNITIVE AGING AND AD. TO DATE, NO STUDY HAS INVESTIGATED HOW AGING AND AD ACT IN CONCERT TO FURTHER IMPAIR THE BLAâS ROLE IN EXTINGUISHING HYPERACTIVE FEAR MEMORIES (A CENTRAL COMPONENT OF PTSD). TO ADDRESS THE CURRENT GAP IN KNOWLEDGE, THIS PROPOSAL WILL LEVERAGE THE TGF34