Whole brain N-acetylaspartate concentration is conserved throughout normal aging

Abstract

We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker--the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)--a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 ± 5.8 years old) and 100 (64 male, 72.6 ± 7.3 years old) cognitively normal elderly. The 12.8 ± 1.9 mM WBNAA of the young was not significantly different from the 13.1 ± 3.1 mM in the elderly (p > 0.05). In contrast, both fBPV (87.3 ± 4.7% vs. 74.8 ± 4.8%) and WHNAA (11.1 ± 1.7 mM vs. 9.8 ± 2.4 mM) were significantly higher in the young (approximately 14%; p < 0.0001 for both). The similarity in mean WBNAA between 2 cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue.

Fig. 1

Left: Sample T₁-weighted MP-RAGE images from 41 (A) and 86 (B) year old males overlaid with their brain parenchyma masks (red). Note the mask correspondence with the underlying anatomy and, for the elderly brain, the relative atrophy incurred in 4 decades of normal aging. Center, A’, B’: Intracranial volume segmentation of A and B with MRIcro. Right, A’’, B”: Whole-head ¹H-MRS spectra from these subjects (not normalized for V_B). Note the NAA peak at 2 ppm, effective lipids suppression performance and that of the other metabolites peaks [most notably the glutamate (Glu), creatine (Cr) and choline (Cho)] only NAA is implicitly localized by its biochemistry to just the brain. Subject NAA peak area, S_S (cross-hatched), for Eq. [1] was obtained by integration.

Fig. 2

Box plots showing the first, second (median) and third quartiles (box) and ±95% (whiskers) and outliers (*) of the WBNAA (top, A), WHNAA (center, B) and fBPV (bottom, C) distributions in healthy young and elderly. Note the WBNAA similar medians as opposed to the significantly lower WHNAA and fBPV in elderly (denoted by the arrows).