Table 1.
In vivo studies with MRS in AD and MCI
| Authors | Disease | Acquisition parameters | Magnet field strength | Single voxel locations | Key findings |
|---|---|---|---|---|---|
| Schuff et al17 | AD | TR/TE= 1800/135 ms | 1.5 T | Frontal, middle, posterior mesial cortex | Decreased NAA frontal and posterior mesial cortex. |
| Zhu et al19 | AD | TR/TE= 1800/25 ms | 1.5 T | Parietal GM, frontal GM, parietal WM, and frontal WM | Decreased NAA/Cr parietal/frontal GM and parietal WM. Increased ml/Cr in parietal GM. |
| Schuff et al31 | AD | TR/TE= 1800/135 ms | 1.5 T | Hippocampus | Decreased NAA/Cr hippocampus. |
| Frederick et al15 | AD | TR/TE = 2000/272 ms | Not reported | Parietal, temporal lobes | Decreased NAA/Cr temporal lobe compared to controls. |
| Jessen et al16 | AD | TR/TE = 2000/272 ms | 1.5 T | Medial temporal lobe and the primary motor and sensory cortex | Decreased NAA/Cr and Cho/Cr medial temporal lobe. |
| Huang et al24 | AD | TR/TE = 3000/30 ms | 1.5 T | Occipital and parietal regions | Decreased NAA/Cr in occipital and parietal regions in AD which changes with severity. Increased ml/Cr in occipital and parietal regions even in mild AD. |
| Chantal et al95 | AD and MCI | TR/TE = 1200/50 ms | 1.5 T | Medial temporal lobes, parietotemporal cortices and prefrontal cortices | AD and MCI demonstrated reductions of NAA/H2O and Cho/H2O in the left MTL, ml/Cr increased in AD relative to MCI and controls in medial temporal lobe. |
| Kantarci et al50 | AD and MCI | TR/TE = 2000/30 ms | 1.5 T | Posterior cingulate | NAA/Cr AD < MCI = control. ml/Cr AD > Controls. |
| Shinno et al58 | AD | TR/TE = 1500/30 ms | 1.5 T | Posterior cingulate, anterior cingulate | NAA/Cr positively correlated and ml/Cr negatively correlated to cognitive tests in the posterior but not anterior cingulate. Behavioral symptoms of dementia negatively related with NAA/Cr and positively related with ml/Cr in the anterior cingulate gyrus, but not in the posterior cingulate. |
| Modrego et al10 | AD | TR/TE = 2500/30 ms | 1.5 T | Frontal, parietal and occipital cortices | Rivastigmine treatment reversed NAA/Cr decrease in frontal cortex only. |
| Miller et al13 | AD | TR/TE = 1500/30 ms | 1.5 T | Parietal WM and occipital GM | Decreased NAA/Cr in occipital GM and parietal WM in AD. Increased ml/Cr in occipital GM and parietal WM. |
| Shonk et al14 | AD | TR/TE = 1500/30 ms | Not reported | Occipital grey matter | Reduced NAA/Cr and increase in ml/Cr in occipital grey matter in AD. |
| Tedeschi et al18 | AD | TR/TE = 2200/272 ms | 1.5 T | Frontal, temporal, parietal, occipital, and insular cortices, subcortical WM, and thalamus | Reduction of NAA/Cr in the frontal, temporal, parietal cortices in AD. Reduction of Cho/Cr in the WM. |
| Kantarci et al25 | AD | TR/TE = 2000/30 ms | 1.5 T | Posterior cingulate | Reduced NAA/Cr and increase in ml/Cr and elevated Cho/Cr in AD compared to controls. |
| Meyerhoff et al26 | AD | Not reported | 2T | Centrum semiovale containing white and mesial grey matter | Reduced NAA/Cr in WM of AD. Posterior section of the centrum semiovale in patients showed increased Cho/Cr compared to controls. |
| Krishnan et al28 | AD | TR/TE = 1200/35 ms | 1.5 T | Subcortical gray, periventricular, cortical, and WM at the level of the third ventricle | Elevated NAA in the donepezil-treated compared to placebo controls. |
| Rose et al30 | AD | TR/TE = 2000/30 ms | 1.5 T | Parietal lobes | NA/Cr was significantly reduced in the AD group with increase in ml/Cr. Metabolite measures also correlated with atrophy. |
| Satlin et al35 | AD | TR/TE = 2 sec/272 ms | 1.5 T | Parietal lobe | For patients taking xanomeline, there was a decrease in Cho/Cr. |
| Kantarci et al36 | AD and MCI | TR/TE = 2000/30 ms | 1.5 T | Posterior cingulate | NAA/Cr declined in MCI and AD patients compared to controls. Cho/Cr declined in stable MCI, compared to converter MCI patients. |
| Hattori et al38 | AD | TR/TE = 6 s/25 ms | 3T | Posterior cingulate gyrus and the precuneus and parietoccipital WM | NA/Cr decreased in both regions in AD. Decrease in the glutamate+Glu/Cr and were detected in the grey matter, but not in the white matter. |
| Bartha et al39 | AD | TR/TE = 3200/46 ms | 4T | Hippocampus | Decreased NAA/Cr, Cho/Cr, and ml/Cr were observed in AD patients after 4 months of donepezil treatment. |
| Rupsingh et al40 | AD | TR/TE = 2.2 s/46 ms | 4T | Hippocampus | Subjects with AD had decreased glutamate as well as decreased Glu/Cr, Glu/ml, Glu/NAA, and NAA/Cr ratios compared to controls. |
| Penner et al41 | AD | TR/TE = 3200/46 ms | 4T | Right hippocampus | Levels of Glu, Glu/Cr, and Glu/NAA increased after 4 months of treatment with galantamine compared to controls. |
| Schott et al47 | AD | TR/TE = 2000/30 ms | 1.5 T | Posterior cingulate | Decreased NAA/Cr in post cingulate. Increased ml/Cr in post cingulate. NAA/ml declines over time in AD compared to controls. |
| Ackl et al48 | AD and MCI | TR/TE = 2000/35 ms for the parietal white and grey matter and TE = 70 ms for the hippocampus on the left cerebral hemisphere | 1.5 T | Parietal gray and white matter and the hippocampus | NAA/Cr was reduced in the hippocampus of MCI and AD. AD had elevated ml/Cr PGM, reduced NAA/Cr in PWM. |
| Schuff et al56 | AD | TR/TE = 1800/135 ms | 1.5 T | Medial temporal, frontal, parietal gray and white matter | NAA concentration was less in AD in the medial temporal lobe and parietal grey matter, but not white matter and frontal lobe GM. Lower NAA AD patients had smaller hippocampi and less cortical GM. |
| Metastasio et al60 | MCI | TR/TE = 2000/40 ms | 1.5 T | Paratrigonal WM | Patients with MCI who progressed to dementia had lower NAA/Cr at baseline than stable MCI. |
| Kantarci et al61 | MCI | TR/TE = 2000/30 ms | 1.5 T | Posterior cingulate | NAA/Cr can predict conversion from MCI to dementia. |
| Mckay et al64 | AD and VaD | TR/TE = 3000/30 and 80 ms | 2T | Anterior, medial, and posterior GM and WM | Lower NAA/Cr compared to controls. High Cho/Cr in posterior regions compared to controls. Lower NAA/Cr in VaD compared to controls. |
| Schuff et al65 | AD and VaD | TR/TE = 1800/135 ms | 1.5 T | Frontal, parietal, temporal cortex | Compared to controls, VaD had lower NAA in frontal and parietal cortex. Compared to patients with AD, VaD had lower NAA in frontal cortex and parietal cortex. |
| Waldman et al67 | AD, VaD | TR/TE = 1500/30 ms | 1 T | Occipital GM | AD had higher ml/Cr compared to those with VaD and normal subjects. |
| Mihara et al68 | AD, FTD | TR/TE = 6000/25 ms | 3T | Posterior and anterior cingulate cortices and the parietoccipital and frontal white matter | NAA/Cr reduced in the posterior cingulate cortex in AD and FTD. AD showed a posterior dominant decrease, whereas FTD showed a frontal decrease. |
| Ernst et al70 | AD, FTD | TR/TE = 3000/30 ms | 1.5 T | Midfrontal and temporoparietal gray matter | FTD showed reduced NAA and glutamate plus glutamine and increased ml. In AD, no abnormalities were observed in the frontal region, but ml was elevated in the temporoparietal region. |
Abbreviations: AD, Alzheimer’s disease; Cho, choline, Cr, creatine; FTD, frontotemporal dementia; Glu, glutamate; GM, grey matter; ml/, myo-inositol; MCI, mild cognitive impairment; NAA, N-acetyl aspartate; PGM, parietal grey matter; PWM, parietal white matter; T, tesla; TE, echo time; TR, repetition time; WM, white matter; VaD, vascular dementia.