# Aging, PTSD, and the Anterior Cingulate Cortex (ACC)

> **NIH VA I01** · MINNEAPOLIS VA  MEDICAL CENTER · 2024 · —

## Abstract

America is aging; baby boomers are now seniors. Staying mentally astute is essential not only for economic
survival but also for quality of life. Yet, the pathophysiology of cognitive aging remains ill-defined, a gap
preventing development of novel diagnostic, therapeutic, or preventive strategies. This laboratory has identified
the anterior cingulate cortex (ACC), the major component of the anterior attention system, as the principal
region showing metabolic decline from young to late adulthood. This decline correlates with declining executive
functions such as fluency. The ACC mediates statistically the relationship between increasing age and
decreasing verbal fluency. Amyloid-free, cognitively intact elders show robust executive but lesser mnemonic
deficits. This project will test the hypothesis that ACC dysfunction in the elderly free of preclinical Alzheimer’s
disease (AD) is associated with redox dysfunction related to aging and severe stress, the latter as seen in
PTSD. Oxidative stress will be measured with 7 T MRI/MRS using the NAD+/NADH ratio, a method developed
here recently. Two factors will include: AGE (younger vs. older) and STRESS (healthy vs. chronic active
PTSD). Neuropsychological testing and plasma phospho-tau181 [or 217] will confirm absence of preclinical AD
as well as revisit the unusual observation: absence of aging-related memory impairment (Logical Memory I &
II) —typically viewed as the sine qua non for aging. The anticipated outcomes are 1) the ACC undergoes redox
stress related to aging and possibly emotional stress; 2) increasing ACC redox stress will correlate with
declining ACC metabolism in the absence of preclinical AD; both will correlate more with declining executive
and less with memory dysfunction; 3) ACC metabolism or redox status may serve as a biomarker for cognitive
aging in the absence of neurodegeneration; and 4) scientific premise and infrastructure will poise the field to
test the potential of antioxidant therapies in preventing or delaying cognitive aging. If successful, aging
American would remain mentally sharp for more years. Since the ACC also participates in cognitive reserve,
secondary prevention would delay symptoms even if neurodegeneration occurs.

## Key facts

- **NIH application ID:** 11132587
- **Project number:** 5I01CX002371-03
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** JOSE V PARDO
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11132587

## Citation

> US National Institutes of Health, RePORTER application 11132587, Aging, PTSD, and the Anterior Cingulate Cortex (ACC) (5I01CX002371-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11132587. Licensed CC0.

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