Magnetic resonance spectroscopy in Alzheimer’s disease

Figures & data

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 al^Citation17	AD	TR/TE= 1800/135 ms	1.5 T	Frontal, middle, posterior mesial cortex	Decreased NAA frontal and posterior mesial cortex.
Zhu et al^Citation19	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 al^Citation31	AD	TR/TE= 1800/135 ms	1.5 T	Hippocampus	Decreased NAA/Cr hippocampus.
Frederick et al^Citation15	AD	TR/TE = 2000/272 ms	Not reported	Parietal, temporal lobes	Decreased NAA/Cr temporal lobe compared to controls.
Jessen et al^Citation16	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 al^Citation24	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 al^Citation95	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 al^Citation50	AD and MCI	TR/TE = 2000/30 ms	1.5 T	Posterior cingulate	NAA/Cr AD < MCI = control. ml/Cr AD > Controls.
Shinno et al^Citation58	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 al^Citation10	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 al^Citation13	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 al^Citation14	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 al^Citation18	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 al^Citation25	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 al^Citation26	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 al^Citation28	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 al^Citation30	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 al^Citation35	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 al^Citation36	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 al^Citation38	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 al^Citation39	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 al^Citation40	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 al^Citation41	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 al^Citation47	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 al^Citation48	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 al^Citation56	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 al^Citation60	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 al^Citation61	MCI	TR/TE = 2000/30 ms	1.5 T	Posterior cingulate	NAA/Cr can predict conversion from MCI to dementia.
Mckay et al^Citation64	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 al^Citation65	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 al^Citation67	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 al^Citation68	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 al^Citation70	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.

Figure 1 Association between MRS metabolite ratios and cortical Pittsburgh compound-B (PiB) retention ratio on PET.

Notes: The left panel shows the PiB retention ratio PET images in an 82-year-old man with a PiB retention ratio of 2.42, NAA/Cr ratio of 1.51, mi/Cr ratio of 0.58, and Cho/Cr ratio of 0.76. The right panel shows the PiB retention ratio in a 78 year-old woman with a PiB retention ratio PET images of 1.27, NAA/Cr ratio of 1.69, mi/Cr ratio of 0.45, and Cho/Cr ratio of 0.54. The spectra are scaled to the Cr peak. High PiB retention is associated with significantly elevated mI/Cr and Cho/Cr ratio and a trend of lower NAA/Cr ratio.
Abbreviations: Cho, choline; Cr, creatine; mi, myo-inositol; MRS, magnetic resonance spectroscopy; NAA, N-acetyl aspartate; PET, positron emission tomography.

SchuffNAmendDLMeyerhoffDJAlzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brainRadiology19982071911029530304

 PubMed Web of Science ®Google Scholar

ZhuXSchuffNKornakJEffects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imagingAlzheimer Dis Assoc Disord2006202778516772742

 PubMed Web of Science ®Google Scholar

SchuffNAmendDEzekielFChanges of hippocampal N-acetyl aspartate and volume in Alzheimer’s disease. A proton MR spectroscopic imaging and MRI studyNeurology1997496151315219409338

 PubMed Web of Science ®Google Scholar

FrederickBBSatlinAYurgelun-ToddDARenshawPFIn vivo proton magnetic resonance spectroscopy of Alzheimer’s disease in the parietal and temporal lobesBiol Psychiatry19974221471509209733

 PubMed Web of Science ®Google Scholar

JessenFBlockWTraberFProton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with ADNeurology200055568468810980734

 PubMed Web of Science ®Google Scholar

HuangWAlexanderGEChangLBrain metabolite concentration and dementia severity in Alzheimer’s disease: a (1)H MRS studyNeurology200157462663211524470

 PubMed Web of Science ®Google Scholar

ChantalSBraunCMBouchardRWLabelleMBoulangerYSimilar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer diseaseBrain Res200410031–2263515019560

 PubMed Web of Science ®Google Scholar

KantarciKSmithGEIvnikRJ1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer’s diseaseJ Int Neuropsychol Soc20028793494212405545

 PubMed Web of Science ®Google Scholar

ShinnoHInagakiTMiyaokaTA decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer’s diseaseJ Neurol Sci20072601–213213817540407

 PubMed Web of Science ®Google Scholar

ModregoPJPinaMAFayedNDiazMChanges in metabolite ratios after treatment with rivastigmine in Alzheimer’s disease: a nonrandomised controlled trial with magnetic resonance spectroscopyCNS Drugs2006201086787716999455

 PubMed Web of Science ®Google Scholar

MillerBLMoatsRAShonkTErnstTWoolleySRossBDAlzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopyRadiology199318724334378475286

 PubMed Web of Science ®Google Scholar

ShonkTKMoatsRAGiffordPProbable Alzheimer disease: diagnosis with proton MR spectroscopyRadiology1995195165727892497

 PubMed Web of Science ®Google Scholar

TedeschiGBertolinoALundbomNCortical and subcortical chemical pathology in Alzheimer’s disease as assessed by multislice proton magnetic resonance spectroscopic imagingNeurology19964736967048797467

 PubMed Web of Science ®Google Scholar

KantarciKPetersenRCBoeveBF1H MR spectroscopy in common dementiasNeurology20046381393139815505154

 PubMed Web of Science ®Google Scholar

MeyerhoffDJMacKaySConstansJMAxonal injury and membrane alterations in Alzheimer’s disease suggested by in vivo proton magnetic resonance spectroscopic imagingAnn Neurol199436140478024260

 PubMed Web of Science ®Google Scholar

KrishnanKRCharlesHCDoraiswamyPMRandomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer’s diseaseAm J Psychiatry2003160112003201114594748

 PubMed Web of Science ®Google Scholar

RoseSEde ZubicarayGIWangDA 1H MRS study of probable Alzheimer’s disease and normal aging: implications for longitudinal monitoring of dementia progressionMagn Reson Imaging199917229129910215485

 PubMed Web of Science ®Google Scholar

SatlinABodickNOffenWWRenshawPFBrain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer’s disease: changes after treatment with xanomeline, an M1 selective cholinergic agonistAm J Psychiatry199715410145914619326834

 PubMed Web of Science ®Google Scholar

KantarciKWeigandSDPetersenRCLongitudinal 1H MRS changes in mild cognitive impairment and Alzheimer’s diseaseNeurobiol Aging20072891330133916860440

 PubMed Web of Science ®Google Scholar

HattoriNAbeKSakodaSSawadaTProton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer’s diseaseNeuroreport200213118318611924885

 PubMed Web of Science ®Google Scholar

BarthaRSmithMRupsinghRRylettJWellsJLBorrieMJHigh field (1)H MRS of the hippocampus after donepezil treatment in Alzheimer diseaseProg Neuropsychopharmacol Biol Psychiatry200832378679318252268

 PubMed Web of Science ®Google Scholar

RupsinghRBorrieMSmithMWellsJLBarthaRReduced hippocampal glutamate in Alzheimer diseaseNeurobiol Aging201132580281019501936

 PubMed Web of Science ®Google Scholar

PennerJRupsinghRSmithMWellsJLBorrieMJBarthaRIncreased glutamate in the hippocampus after galantamine treatment for Alzheimer diseaseProg Neuro-Psychopharmacol Biol Psychiatry2010341104110

 Web of Science ®Google Scholar

SchottJMFrostCMacManusDGIbrahimFWaldmanADFoxNCShort echo time proton magnetic resonance spectroscopy in Alzheimer’s disease: a longitudinal multiple time point studyBrain2010133113315332220739347

 PubMed Web of Science ®Google Scholar

AcklNIsingMSchreiberYAAtiyaMSonntagAAuerDPHippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer’s diseaseNeurosci Lett20053841–2232815905028

 PubMed Web of Science ®Google Scholar

SchuffNCapizzanoAADuATSelective reduction of N- acetylaspartate in medial temporal and parietal lobes in ADNeurology200258692893511914410

 PubMed Web of Science ®Google Scholar

MetastasioARinaldiPTarducciRConversion of MCI to dementia: role of proton magnetic resonance spectroscopyNeurobiol Aging200627792693215936850

 PubMed Web of Science ®Google Scholar

KantarciKWeigandSDPrzybelskiSARisk of dementia in MCI: combined effect of cerebrovascular disease, volumetric MRI, and 1H MRSNeurology200972171519152519398707

 PubMed Web of Science ®Google Scholar

MacKaySMeyerhoffDJConstansJMNormanDFeinGWeinerMWRegional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imagingArch Neurol19965321671748639067

 PubMedGoogle Scholar

SchuffNCapizzanoAADuATDifferent patterns of N- acetylaspartate loss in subcortical ischemic vascular dementia and ADNeurology200361335836412913198

 PubMed Web of Science ®Google Scholar

WaldmanADRaiGSMcConnellJRChaudryMGrantDClinical brain proton magnetic resonance spectroscopy for management of Alzheimer’s and sub-cortical ischemic vascular dementia in older peopleArch Gerontol Geriatr200235213714214764351

 PubMed Web of Science ®Google Scholar

MiharaMHattoriNAbeKSakodaSSawadaTMagnetic resonance spectroscopic study of Alzheimer’s disease and frontotemporal dementia/Pick complexNeuroreport200617441341616514368

 PubMed Web of Science ®Google Scholar

ErnstTChangLMelchorRMehringerCMFrontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopyRadiology199720338298369169712

 PubMed Web of Science ®Google Scholar