Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss.

BACKGROUND AND PURPOSE In Alzheimer disease (AD), elevated brain iron concentrations in gray matter suggest a disruption in iron homeostasis, while demyelination processes in white matter increase the water content. Our aim was to assess whether the transverse proton relaxation rate, or R2, an MR imaging parameter affected by changes in brain iron concentration and water content, was different in elderly participants with mild to severe levels of cognitive impairment compared with healthy controls. METHODS Twelve elderly participants reporting memory problems and 11 healthy volunteers underwent single-spin-echo MR imaging in a 1.5T scanner, with subsequent neuropsychological testing. R2 data were collected from 14 brain regions in cortical and subcortical gray and white matter. Those with memory complaints were separated into 2 further subgroups: MC1 (no objective cognitive impairment) and MC2 (mild to severe objective cognitive impairment). RESULTS Mean brain R2 values from the 11 controls correlated strongly (r = 0.94, P < .0001) with reference brain iron concentrations for healthy adults. R2 values in the MC1 and MC2 subgroups were significantly higher in the right temporal cortex and significantly lower in the left internal capsule, compared with healthy controls. R2 values in the MC2 subgroup were significantly lower in the left temporal and frontal white matter, compared with healthy controls. CONCLUSIONS R2 differences between both subgroups and the healthy controls suggest iron has increased in the temporal cortex, and myelin has been lost from several white matter regions in those with memory complaints, consistent with incipient AD pathogenesis and biochemical data.

[1]  F. Gonzalez-Lima,et al.  Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior☆ , 2000, Neurobiology of Aging.

[2]  Mark A. Smith,et al.  Iron: A Pathological Mediator of Alzheimer Disease? , 2002, Developmental Neuroscience.

[3]  W. D. Ehmann,et al.  Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. , 1998, Neurotoxicology.

[4]  A Brun,et al.  White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates. , 1988, Brain : a journal of neurology.

[5]  J. Connor,et al.  Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions , 1995, Journal of neurochemistry.

[6]  R Stewart,et al.  Cerebral white matter lesions and subjective cognitive dysfunction: The Rotterdam Scan Study , 2001, Neurology.

[7]  V. Haughton,et al.  T1 and T2 measurements on a 1.5-T commercial MR imager. , 1989, Radiology.

[8]  G. Bartzokis,et al.  MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease. , 2000, Cellular and molecular biology.

[9]  J. Lucas,et al.  Disorders of memory. , 2005, The Psychiatric clinics of North America.

[10]  R. Bakshi,et al.  T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. , 2002, Archives of neurology.

[11]  Jane S. Paulsen,et al.  In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease , 2004, Neurology.

[12]  D. Schubert,et al.  The role of iron in beta amyloid toxicity. , 1995, Biochemical and biophysical research communications.

[13]  Jim Mintz,et al.  In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI , 1994, Biological Psychiatry.

[14]  Craig K. Jones,et al.  Normal‐appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T2 , 2002, Magnetic resonance in medicine.

[15]  G. Bartzokis,et al.  White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. , 2003, Archives of neurology.

[16]  Huali Wang,et al.  Prolongation of T2 relaxation times of hippocampus and amygdala in Alzheimer's disease , 2004, Neuroscience Letters.

[17]  J. Bulte,et al.  Comparison of t2 relaxation in blood, brain, and ferritin , 1995, Journal of magnetic resonance imaging : JMRI.

[18]  G. Perry,et al.  Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[19]  D. Neary,et al.  Diagnostic value of high signal abnormalities on T2 weighted MRI in the differentiation of Alzheimer's, frontotemporal and vascular dementias , 2002, Acta neurologica Scandinavica.

[20]  Yu-Min Kuo,et al.  Increased Aβ Peptides and Reduced Cholesterol and Myelin Proteins Characterize White Matter Degeneration in Alzheimer's Disease† , 2002 .

[21]  G. Bartzokis Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease , 2004, Neurobiology of Aging.

[22]  P. Mantyh,et al.  Aluminum, Iron, and Zinc Ions Promote Aggregation of Physiological Concentrations of β‐Amyloid Peptide , 1993, Journal of neurochemistry.

[23]  G. Brittenham,et al.  Noninvasive measurement of iron: report of an NIDDK workshop. , 2003, Blood.

[24]  J. Connor,et al.  Regional distribution of iron and iron‐regulatory proteins in the brain in aging and Alzheimer's disease , 1992, Journal of neuroscience research.

[25]  Hisashi Tanaka,et al.  Determination of transverse relaxation rate for estimating iron deposits in central nervous system , 2005, Neuroscience Research.

[26]  K. Krishnan,et al.  Quantitative analysis of T2 signal intensities in Alzheimer's Disease , 1998, Psychiatry Research: Neuroimaging.

[27]  B. Hallgren,et al.  THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN , 1958, Journal of neurochemistry.

[28]  H. Braak,et al.  Alzheimer's disease affects limbic nuclei of the thalamus , 2004, Acta Neuropathologica.

[29]  A Brun,et al.  CORRELATIONS BETWEEN HISTOPATHOLOGIC WHITE MATTER CHANGES AND PROTON MR RELAXATION TIMES IN DEMENTIA , 1987, Alzheimer disease and associated disorders.

[30]  M. Kopelman Disorders of memory. , 2002, Brain : a journal of neurology.

[31]  C. Morris,et al.  Histochemical distribution of non-haem iron in the human brain. , 1992, Acta anatomica.

[32]  Larry L. Butcher,et al.  Prolongation of magnetic resonance T 2 time in hippocampus of human patients marks the presence and severity of Alzheimer's disease , 1992, Neuroscience Letters.

[33]  K. Kristensson,et al.  Lipid Composition in Different Regions of the Brain in Alzheimer's Disease/Senile Dementia of Alzheimer's Type , 1992, Journal of neurochemistry.

[34]  S. M. de la Monte,et al.  Quantitation of cerebral atrophy in preclinical and end‐stage alzheimer's disease , 1989, Annals of neurology.

[35]  P. Scheltens,et al.  White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer’s disease, vascular dementia, and normal aging , 1999, Journal of neurology, neurosurgery, and psychiatry.

[36]  A. Nunomura,et al.  Oxidative Damage Is the Earliest Event in Alzheimer Disease , 2001, Journal of neuropathology and experimental neurology.

[37]  J. O'Brien,et al.  Comparison of the pathology of cerebral white matter with post‐mortem magnetic resonance imaging (MRI) in the elderly brain , 2004, Neuropathology and applied neurobiology.

[38]  P D Griffiths,et al.  Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson's disease and Alzheimer's disease. , 1993, Dementia.

[39]  E. Englund,et al.  Glial levels determine severity of white matter disease in Alzheimer's disease: a neuropathological study of glial changes , 2003, Neuropathology and applied neurobiology.

[40]  P. Riekkinen,et al.  2′,3′-Cyclic nucleotide-3′-phosphodiesterase activity as an index of myelin in the post-mortem brains of patients with Alzheimer's disease , 1989, Neuroscience Letters.

[41]  H. Soininen,et al.  Severity of hippocampal atrophy correlates with the prolongation of MRI T sub 2 relaxation time in temporal lobe epilepsy but not in Alzheimer's disease , 1996, Neurology.

[42]  G A Johnson,et al.  In vitro MR microscopy of the hippocampus in Alzheimer's disease , 1993, Neurology.

[43]  J. Besson,et al.  Post-mortem Proton Magnetic Resonance Spectrometric Measures of Brain Regions in Patients with a Pathological Diagnosis of Alzheimer's Disease and Multi-infarct Dementia , 1992, British Journal of Psychiatry.

[44]  R. Brooks,et al.  T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. , 1999, Radiology.

[45]  Stavros J. Baloyannis,et al.  Mitochondrial alterations in Alzheimer's disease. , 2006, Journal of Alzheimer's disease : JAD.

[46]  G E Santyr,et al.  Magnetization transfer effects in multislice MR imaging. , 1993, Magnetic resonance imaging.

[47]  T. S. St. Pierre,et al.  Single spin‐echo proton transverse relaxometry of iron‐loaded liver , 2004, NMR in biomedicine.

[48]  Douglas Walker,et al.  Increased A beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease. , 2002, Biochemistry.

[49]  A. Delacourte,et al.  The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease , 1999, Neurology.

[50]  Steven M LeVine,et al.  Iron deposits in multiple sclerosis and Alzheimer's disease brains , 1997, Brain Research.

[51]  H. Soininen,et al.  MR T2 relaxometry in Alzheimer's disease and age-associated memory impairment , 1996, Neurobiology of Aging.

[52]  W. D. Ehmann,et al.  Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress , 1996, Journal of the Neurological Sciences.

[53]  C. Jack,et al.  Hippocampal transverse relaxation times in patients with Alzheimer disease. , 1997, Radiology.

[54]  W. D. Ehmann,et al.  Regional brain trace-element studies in Alzheimer's disease. , 1988, Neurotoxicology.

[55]  R A Knight,et al.  MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. , 1999, Radiology.