# Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $1

## Abstract

Project Summary
The ultimate goal of this project is to gain knowledge about the order and nature of metabolic mechanisms that
underlie the shift from healthy human brain aging to the pathological processes that are associated with
Alzheimer's disease, and to relate such order to age-associated alterations in connectivity, structure and
microstructure. The first step will be to find out whether the trajectories of neurochemical concentrations over
the age span are similar among the posterior cingulate cortex (PCC) and the frontal cortex (FC), or if one
region progresses at a younger age than the other. The PCC and FC are key functionally connected systems
within the default mode network (DMN), which is one of the most relevant brain networks for aging and
Alzheimer's disease. Our hypothesis is that the frontal cortex (FC), which shows signs of deterioration early
during healthy aging will evidence age-associated alterations in neurochemistry at a younger age than the
posterior cingulate cortex (PCC), and the pathology associated with Alzheimer's disease in the PCC will be
evidenced by an altered neurochemical profile. The next step will be to find out whether the trajectory of
neurochemistry precedes or follows trajectories of functional, structural and microstructural brain changes. The
project will also allow determining whether a combination of neurochemical concentrations and MRI outcomes
can be effectively used to distinguish healthy aging from Alzheimer's' disease. The influence of genetic and
health factors on all of these phenomena will also be explored. This study is designed to take advantage of
state-of-the art imaging data that will be extant within the national human connectome project on aging (HCPA)
and the Minnesota Alzheimer's connectome project (MACP). Detailed image-based information on function,
structure and microstructure will be extracted from the connectome images from the exact same FC and PCC
volumes of interest as magnetic resonance (MR) spectra will be measured from. A powerful MR scanner will
be used to detect neurochemicals that are not usually seen, i.e., the antioxidant ascorbate and the putative
indicator of myelination phosphorylethanolamine, as well as the glial marker myo-inositol, the marker of
membrane turnover choline, and the neurotransmitter glutamate. The human cohorts are key aspects of the
study design. Aging will be studied over the range 36 to 89 years old in people who are all known to be
cognitively healthy and free of evidence of incipient Alzheimer's disease. Alzheimer's disease will be studied in
patients who have been highly characterized clinically and metabolically. Incipient Alzheimer's disease will be
studied in older adults who appear to be healthy upon neuropsychological and neurological examination, but
have positive amyloid PET imaging outcomes.

## Key facts

- **NIH application ID:** 10159810
- **Project number:** 5R01AG055591-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Silvia Mangia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-10-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159810

## Citation

> US National Institutes of Health, RePORTER application 10159810, Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network (5R01AG055591-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159810. Licensed CC0.

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