Reduction in regional cerebral metabolic rate of oxygen during human aging.

Yamaguchi, Takekane; Kanno, Iwao; Uemura, Kazunori; Shishido, Fumio; Inugami, A; Ogawa, Toshihide; Murakami, M.T.; Suzuki, Koichi

doi:10.1161/01.str.17.6.1220

Cited by 233 publications

(165 citation statements)

References 33 publications

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“…An absolute CBF value of 40.8 6 4.3 ml/100 g/min in global GM agrees quite well with early PET results, even the variability across brain regions is partly reproduced (5,6). However, these studies exhibit a coarse spatial resolution, and thus certainly suffer from considerable partial volume effects.…”

Section: Discussionsupporting

confidence: 84%

“…CBF corr was significantly reduced in the right superior parietal cortex and precuneus as well as bilateral caudate. Previous studies without PVC but with regional information reported decreasing CBF with increasing age in frontal (5,12,23) and parietal areas (12,23), in the insular cortex (5,23), in the cingulate and parahippocampal cortex (23) as well as a trend in the caudate (6). Even though the imaging volume of our study (parallel to and comprising the hippocampus) did not comprise substantial portions of the frontal cortex, the ROI analysis without PVC revealed significant CBF reductions in inferior frontal and olfactory cortex, and the CBF in the cingulate cortex, the parahippocampus and the insula was somewhat lower in elderly subjects, although insignificantly.…”

Section: Discussionmentioning

confidence: 89%

“…Early investigations of age-related CBF changes using positron emission tomography (PET) or single photon emission computed tomography (SPECT) found a general decline of CBF in whole brain or grey matter (GM) (3,4). More recent PET-based studies explored CBF in selected regions of interest (5,6) and stressed the confounding influence of partial volume effects (7,8) due to atrophy in the ageing brain. In recent years, MRI-based arterial spin labeling (ASL) techniques (9) emerged as scientific tools to investigate brain perfusion in elderly populations (10)(11)(12).…”

mentioning

confidence: 99%

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Age‐related cerebral perfusion changes in the parietal and temporal lobes measured by pulsed arterial spin labeling

Preibisch¹,

Sorg²,

Förschler³

et al. 2011

Magnetic Resonance Imaging

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Purpose: To investigate age-related regional perfusion changes focused on the medial temporal lobes and related parietal areas using a pulsed arterial spin labeling technique. Materials and Methods:Resting cerebral blood flow (CBF) maps were obtained from 44 healthy volunteers (18 male, 26 female; age range, 19 to 79 years) using a pulsed arterial spin labeling (PASL) MRI technique at 3 Tesla focused on the parietal and temporal lobes. Repeated measurements were performed in 20 subjects to assure the reliability and reproducibility of the applied PASL technique.Results: Focal age-related CBF decreases were detected in the parietal cortex, cuneus and caudate, whereas increases were seen in the lateral and medial temporal lobe such as hippocampus, the calcarine gyrus and the thalamus. Moreover, repeated measurements demonstrated a high reliability and reproducibility of the applied PASL technique.Conclusion: Data provide evidence for regionally dissociated patterns of perfusion increases and decreases during ageing in the temporal and parietal lobes.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

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Age‐related cerebral perfusion changes in the parietal and temporal lobes measured by pulsed arterial spin labeling

Preibisch¹,

Sorg²,

Förschler³

et al. 2011

Magnetic Resonance Imaging

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“…Significant CMR O2 reduction and relatively constant CMR glc (i.e., a reduced oxygen-to-glucose index) in older people have been reported (36,37). Moreover, the notion that age-induced decrease in NAD + /NADH RX reflects deficiency in mitochondrial capacity for oxidative phosphorylation is also supported by significant decreases (e.g., 15-34%) in respiratory enzyme (complexes I-V) activities observed in aged mice brains (38), which is in line with another human brain study showing an ∼30% reduction in both neuronal oxidative glucose metabolism and neurotransmission cycling rates in elderly people (39).…”

Section: Discussionmentioning

confidence: 99%

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Zhu

Lü

Lee

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

386

347

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NAD is an essential metabolite that exists in NAD + or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD + /NADH redox state and modulating cellular signaling processes through the activity of the NAD + -dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD + and NADH contents and the NAD + /NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD + , total NAD contents, and NAD + /NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.redox state | NAD | in vivo 31 P MR spectroscopy | human brain | aging N AD, a multifunctional metabolite found in all living cells, has been the interest of many scientific investigations since its discovery in the early 20th century (1). NAD is known to convert between its oxidized NAD + and reduced NADH forms during the breakdown of nutrients; hence, the intracellular NAD + /NADH redox state reflects the metabolic balance of the cell in generating ATP energy through oxidative phosphorylation in mitochondria and/or glycolysis in cytosol (2). More recently, after several protein families associated with cell survival were found to use NAD + as their main substrate with activities also regulated by the availability of the NAD + , the full extent of the NAD's function as a metabolic regulator began to unfold (3-5). A growing number of studies have indicated that NAD + can modulate metabolic signaling pathways and mediate important cellular processes, including calcium homeostasis, gene expression, aging, degeneration, and cell death; therefore, the cellular NAD could serve as a therapeutic target for treating various metabolic or age-related diseases and promoting longevity (6-12).Despite the critical relevance of the intracellular NAD metabolism to human health and diseases, assessment of NAD contents and NAD + /NADH redox state is extremely challenging. Only a few invasive techniques based on biochemical assays or autofluorescence methods have been used to analyze tissue samples or cell extracts (13,14). However, during the preparation of such ex vivo sample, the NAD + and NADH contents are likely altered, beca...

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“…Figure 3) and reasonable absolute values [31][32][33][34], a comparison between calibrated DSC-MRI and pCASL is indeed of interest. Nevertheless, it should be remembered that the value of M0 a scales all the CBF values in a pCASL volume, so the method used to determine M0 a will directly influence the absolute level of CBF.…”

Section: Comparison With Pcaslmentioning

confidence: 63%

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL

Lindgren

Wirestam

Bloch

et al. 2014

Magn Reson Mater Phy

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General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractObjective: Dynamic susceptibility-contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF. Materials and Methods:Twenty healthy volunteers were scanned in a test-retest approach. Independent CBV measurements, for calibration, were accomplished using a T1-based contrast agent steady-state method (referred to as Bookend) as well as a blood-nulling vascular space occupancy (VASO) approach. Calibrated DSC-MRI was compared with pseudo-continuous arterial spin labeling (pCASL).Results: For segmented grey matter (GM) regions of interests (ROIs), pCASL-based CBF was 63±11 ml/(min100g) (mean±SD). Nominal CBF from non-calibrated DSC-MRI was 277±61 ml/(min100g), while calibrations resulted in 56±23 ml/(min100g) (Bookend) and 52±16 ml/(min100g) (VASO). Calibration tended to eliminate the overestimation, although the repeatability was, generally, moderate and the correlation between calibrated DSC-MRI and pCASL was low (r<0.25). However, using GM instead of WM ROIs for extraction of CFs resulted in improved repeatability. Conclusion:Both calibration approaches provided reasonable absolute levels of GM CBF, although the calibration methods suffered from low signal-to-noise ratio, resulting in weak repeatability and difficulties in showing high degrees of correlation with pCASL measurements.3

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Reduction in regional cerebral metabolic rate of oxygen during human aging.

Cited by 233 publications

References 33 publications

Age‐related cerebral perfusion changes in the parietal and temporal lobes measured by pulsed arterial spin labeling

Age‐related cerebral perfusion changes in the parietal and temporal lobes measured by pulsed arterial spin labeling

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL

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