Alterations in Cerebral Metabolic Rate and Blood Supply across the Adult Lifespan

Lu, Hanzhang; Xu, Feng; Rodrigue, Karen M.; Kennedy, James L.; Cheng, Yamei; Flicker, Blair; Hebrank, Andrew; Uh, Jinsoo; Park, Denise C.

doi:10.1093/cercor/bhq224

Cited by 331 publications

(416 citation statements)

References 60 publications

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“…In terms of WM rCBF, one did not observe any differences in SZ while another observed that WM rCBF decreased with age and faster in SZ (Pinkham et al, 2011;Wright et al, 2014). Similarly, this study found an aging effect of AC WM rCBF, which is also consistent with work showing rCBF decrease across life span (Lu et al, 2011).…”

Section: Discussionsupporting

confidence: 90%

Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

Wijtenburg

Wright

Korenic

et al. 2016

Neuropsychopharmacol

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The neurobiology of schizophrenia (SZ) may be altered in older versus younger adults with SZ, as less frequent episodes of symptom exacerbation and increased sensitivity to medications are observed in older age. The goal of this study was to examine the effect of age and diagnosis on glutamate and cerebral blood flow (rCBF) in adults with SZ and healthy controls. Young and older adults with SZ and healthy controls were recruited to participate in this study. Participants completed a neuropsychological battery and neuroimaging that included optimized magnetic resonance spectroscopy to measure anterior cingulate (AC) glutamate (Glu) and glutamine (Gln) and arterial spin labeling evaluation for rCBF. Regression analyses revealed significant effects of age with Glu, Gln, Gln/Glu, and AC white matter (WM) rCBF. Glu and WM rCBF decreased linearly with age while Gln and Gln/Glu increased linearly with age. Glu was lower in adults with SZ compared with healthy controls and in older adults versus younger adults but there was no interaction. Glu and WM rCBF were correlated with the UCSD Performance-Based Skills Assessment (UPSA) and processing speed, and the correlations were stronger in the SZ group. In the largest sample to date, lower Glu and elevated Gln/Glu levels were observed in adults with SZ and in older subjects. Contrary to expectation, these results do not show evidence of accelerated Glu aging in the anterior cingulate region in SZ compared with healthy controls.

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Section: Discussionsupporting

confidence: 90%

Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

Wijtenburg

Wright

Korenic

et al. 2016

Neuropsychopharmacol

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“…Finally, GM CVR in elderly was significantly lower (Po0.001) than that in young, which is relatively well established from the previous literature. 36,37 Further analysis was performed to test the possibility that the WM time course is best matched by the convolution of the GM time course with an exponential dispersion function, rather than by simply shifting the GM time course. The optimal time constant for the exponential function was found to be 26 ± 5 and 8±2 seconds for younger and older subjects, respectively, with a significant group difference (P ¼ 0.004).…”

Section: Resultsmentioning

confidence: 99%

Cerebrovascular Reactivity in the Brain White Matter: Magnitude, Temporal Characteristics, and Age Effects

Thomas

Liu

Park³

et al. 2013

J Cereb Blood Flow Metab

Self Cite

109

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White matter (WM) comprises about half of the brain and its dysfunction is implicated in many brain disorders. While structural properties in healthy and diseased WM have been extensively studied, relatively little is known about the physiology underlying these structural characteristics. Recent advances in magnetic resonance (MR) technologies provided new opportunities to better understand perfusion and microvasculature in the WM. Here, we aim to evaluate vasodilatory capacity of the WM vasculature, which is thought to be important in tissue ischemia and autoregulation. Fifteen younger and fifteen older subjects performed a CO 2 inhalation task while blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging (MRI) images were continuously collected. The cerebrovascular reactivity (CVR) index showed that the value of CVR in the WM (0.03±0.002%/mm Hg) was positive, but was significantly lower than that in the gray matter (GM) (0.22 ± 0.01%/mm Hg). More strikingly, the WM response showed a temporal delay of 19 ± 3 seconds compared with GM, which was attributed to the longer time it takes for extravascular CO 2 to change. With age, WM CVR response becomes greater and faster, which is opposite to the changes seen in the GM. These data suggest that characteristics of WM CVR are different from that of GM and caution should be used when interpreting pathologic WM CVR results.

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“…However, it is important to emphasize that lower baseline CBF does not mean lower brain metabolism (oxygen or glucose) in the context of aging. In fact, recent literature suggested that baseline brain oxygen metabolic rate is greater in the older individuals (Lu et al 2011), presumably related to lower efficiency in mitochondria and neuronal functions. This concomitant increase in metabolic demand and decrease in blood supply of course will result in a higher oxygen extraction fraction (OEF) with age, which has been confirmed as well (Lu et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

Chiu

Mak

Yau

et al. 2013

AGE

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Magnetic resonance spectroscopy (MRS) can explore aging at a molecular level. In this study, we investigated the relationships between regional concentrations of metabolites (such as choline, creatine, myo-inositol, and N-acetyl-aspartate) and normal aging in 30 cognitively normal subjects (15 women and 15 men, age range 22-82, mean=49.9±18.3 years) using quantitative proton magnetic resonance spectroscopy. All MR scans were performed using a 3 T scanner. Point resolved spectroscopy was used as the volume selection method for the region-of-interest and the excitation method for water suppression. Single voxel spectroscopy with short echo time of 39 ms and repetition time of 2,000 ms was employed.Single voxels were placed in the limbic regions, i.e., anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and left and right hippocampi. Cerebrospinal fluid normalization and T1 and T2 correction factors were implemented in the calculation of absolute metabolite concentrations. A standardized T1W 3D volumetric fast field echo and axial T2-weighted fast spin-echo images were also acquired. Our results showed significant positive correlation of choline (r=0.545, p=0.002), creatine (r=0.571, p=0.001), and N-acetyl-aspartate (r= 0.674, p<0.001) in the ACC; choline (r=0.614, p< 0.001), creatine (r=0.670, p<0.001), and N-acetyl-aspartate (r=0.528, p=0.003) in the PCC; and NAA (r=0.409, p=0.025) in the left hippocampus, with age. No AGE (2014) significant gender effect on metabolite concentrations was found. In aging, increases in choline and creatine might suggest glial proliferation, and an increase in Nacetyl-aspartate might indicate neuronal hypertrophy. Such findings highlight the metabolic changes of ACC and PCC with age, which could be compensatory to an increased energy demand coupled with a lower cerebral blood flow.

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Alterations in Cerebral Metabolic Rate and Blood Supply across the Adult Lifespan

Cited by 331 publications

References 60 publications

Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

Altered Glutamate and Regional Cerebral Blood Flow Levels in Schizophrenia: A 1H-MRS and pCASL study

Cerebrovascular Reactivity in the Brain White Matter: Magnitude, Temporal Characteristics, and Age Effects

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

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