Table 2.

Brain changes associated with HIV and aging: MRS and fMRI studies

Reference	Subjects	ARV therapy	Brain regions or network evaluated	Findings	Aging effect(s)
MRS studies
Ernst and Chang, AIDS 2004	46 HIV+ (92 % male); mean age, 36.1  (18–58 years); 58 SN (28 % male);  mean age, 51.5 (19-78 years)	Naïve	Frontal WM,  frontal GM, BG	Compared with SN controls, HIV subjects showed additional and  marked increases in the concentration of glial markers, CHO  (SN, +2 %/decade; HIV, +10 %/decade) and MI (SN, +3 %/decade;  HIV, +12 %/decade), with aging in the frontal WM. In the BG, NA  and tCr decreased with age only in HIV patients (NA, −3.7 %/decade;  tCr, −4 %/decade).	Accelerated  aging
Chang et al., Neuroimage 2004a	39 HIV+ NAS (87 % male, 19–51 years);  61 HIV+ ADC (89 % male, 31–63 years);  37 SN (49 % male, 19–58 years)	82; 98 %	Frontal WM,  parietal GM, BG	HIV infection and aging had additive effects on elevated Cho/Cr and  Ml/Cr in the BG and WM. Younger (<40 years) HIV subjects showed  lower NAA/tCr than younger SN in frontal WM, which may reflect  greater inflammatory response in younger subjects, leading to  enhanced neuronal injury.	Premature  aging
Ernst et al., JMRI 2010,	27 HIV+ NC (96 % male, 46.7±1.9 years);  18 HIV+ HAND (89 % male, 44.9±2.5 years);  45 SN (80 % male, age 43.3±1.8 years)	Not specified	Parietal GM, frontal  WM, frontal GM, BG	GLU levels in HIV+ subjects were equivalent to those of SN subjects  approximately 10 years older.	Premature  aging
Harenzlak et al., AIDS 2011	124 HIV+ NAS (83 % male, 44.5 years);  66 HIV+ ADC 0.5 (85 % male, 48.5 years);  50 HIV+ ADC >1 (90 % male, 47.9 years);  28 SN (36 % male, 53.0 years); all subjects  (ages 30–70 years)	100 %	Frontal WM,  fronal GM, BG	HIV effect: HIV subjects had higher Ml/Cr Cho/Cr in all brain regions,  lower Glx/tCr in the frontal WM only in the NAS group, and lower  NA/tCr only in the ADC group. Age-dependent decrease in NA/tCr  medial frontal cortex and age-dependent decline in Glx/tCr in the frontal  WM (HIV subjects at age 30 years equivalent to SN subject at age 56 years).  Ml/Cr in frontal WM increased with age in NAS and ADC 0.5 subjects, but  decreased with age for ADC >1.	Premature  aging
Brain network studies
Ernst et al., Ann Neurol 2009	31 HIV+ (97 % male, 49.6±1.5 years); 32 SN  (87 % male, 46.9±2.3 years)	100 %	Visual attention	Over 1 year, HIV patients showed no change in their neurocognitive status  or in task performance during fMRI. However, HIV patients showed  significant 1-year increases in fMRI signals in the prefrontal and posterior  parietal cortices for the more difficult tasks, whereas SN control participants  showed only decreases in brain activation in these regions.	Premature  aging
Ances et al., J. Infect Dis 2010	26 HIV+ (77 % male, 39 years); 25 SN  (56 % male, 41 years); age range, 20–62 years	60 %	Primary visual  stimulation	HIV+ had lower baseline CBF, but no interaction between HIV and age.  HIV+ equivalent to SN plus 15 years. HIV+ had greater functional CBF  increases, as did age, but no interaction. HIV+ equal to SN plus 21 years.  HIV+ had reduced BOLD, as did age, but no interaction. HIV+ equivalent  to SN plus 15 years.	Premature  aging