Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease

BACKGROUND Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (NC) mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed. METHODS We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (FA) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE). RESULTS Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable. CONCLUSIONS Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression.

[1]  P. Rabbitt,et al.  Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. , 1994, Dementia.

[2]  N. Schuff,et al.  Headache and cerebral venous air embolism , 2007, Neurology.

[3]  J. Schneider,et al.  Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions , 2005, Neurology.

[4]  Andrea Federspiel,et al.  Examining the gateway to the limbic system with diffusion tensor imaging: The perforant pathway in dementia , 2006, NeuroImage.

[5]  R. Petersen,et al.  Development of Cognitive Instruments for Use in Clinical Trials of Antidementia Drugs: Additions to the Alzheimer's Disease Assessment Scale That Broaden Its Scope , 1997, Alzheimer disease and associated disorders.

[6]  A. Kamel,et al.  Address for correspondence , 2000 .

[7]  Matthias J. Müller,et al.  Functional relevant loss of long association fibre tracts integrity in early Alzheimer's disease , 2008, Neuropsychologia.

[8]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[9]  Takashi Inoue,et al.  Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging , 2002, Neuroscience Letters.

[10]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[11]  D. Zaitchik,et al.  Predicting conversion to Alzheimer disease using standardized clinical information. , 2000, Archives of neurology.

[12]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[13]  Jie Xu,et al.  White matter damage of patients with Alzheimer’s disease correlated with the decreased cognitive function , 2006, Surgical and Radiologic Anatomy.

[14]  Nick C Fox,et al.  The Alzheimer's disease neuroimaging initiative (ADNI): MRI methods , 2008, Journal of magnetic resonance imaging : JMRI.

[15]  Marilyn S. Albert,et al.  Research consent for cognitively impaired adults: recommendations for institutional review boards and investigators. , 2004, Alzheimer disease and associated disorders.

[16]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[17]  C. Oppenheim,et al.  Diffusion tensor imaging in early Alzheimer's disease , 2006, Psychiatry Research: Neuroimaging.

[18]  George Bartzokis,et al.  Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations. , 2007, Brain : a journal of neurology.

[19]  Hangyi Jiang,et al.  DtiStudio: Resource program for diffusion tensor computation and fiber bundle tracking , 2006, Comput. Methods Programs Biomed..

[20]  R. Petersen.  Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[21]  E. Kaplan,et al.  Integrating clinical assessment with cognitive neuroscience: construct validation of the California Verbal Learning Test. , 1988, Journal of consulting and clinical psychology.

[22]  S. Rose,et al.  Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[23]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[24]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[25]  P. Albert,et al.  Models for longitudinal data: a generalized estimating equation approach. , 1988, Biometrics.

[26]  A. Auchus,et al.  Diffusion Tensor Imaging of Normal Appearing White Matter and Its Correlation with Cognitive Functioning in Mild Cognitive Impairment and Alzheimer's Disease , 2007, Annals of the New York Academy of Sciences.

[27]  J. Morris,et al.  Mild cognitive impairment as a clinical entity and treatment target. , 2005, Archives of neurology.

[28]  R. Reitan.  Trail Making Test: Manual for Administration and Scoring , 1992 .

[29]  D. Bennett,et al.  White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study , 2006, Neurobiology of Aging.

[30]  D. Head,et al.  Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. , 2004, Cerebral cortex.

[31]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[32]  S. Schoenberg,et al.  White matter damage in Alzheimer disease and mild cognitive impairment: assessment with diffusion-tensor MR imaging and parallel imaging techniques. , 2007, Radiology.

[33]  Maximilian Reiser,et al.  Multivariate network analysis of fiber tract integrity in Alzheimer’s disease , 2007, NeuroImage.

[34]  Ke-Min Chen,et al.  Diffusion Tensor Imaging Correlates with Proton Magnetic Resonance Spectroscopy in Posterior Cingulate Region of Patients with Alzheimer’s Disease , 2008, Dementia and Geriatric Cognitive Disorders.

[35]  B. Reisberg,et al.  Diffusion Tensor Imaging of Frontal White Matter Microstructure in Early Alzheimer’s Disease: A Preliminary Study , 2005, Journal of geriatric psychiatry and neurology.

[36]  Camilla Anne Czubaj.  The Wechsler Adult Intelligence Scale - Revised, Revisited , 1996 .

[37]  J. Morris.  The Clinical Dementia Rating (CDR) , 1993, Neurology.

[38]  M. Mega,et al.  The Neuropsychiatric Inventory , 1994, Neurology.

[39]  Harald Hampel,et al.  Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study. , 2007, Cerebral cortex.

[40]  A. Nappi,et al.  Alzheimer ' s Disease : Cell-Specific Pathology Isolates the Hippocampal Formation , 2022 .

[41]  M. Filippi,et al.  White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging , 2002, Journal of neurology, neurosurgery, and psychiatry.

[42]  H. Braak,et al.  Evolution of the neuropathology of Alzheimer's disease , 1996, Acta neurologica Scandinavica. Supplementum.

[43]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[44]  Y. Zang,et al.  Voxel-based detection of white matter abnormalities in mild Alzheimer disease , 2006, Neurology.

[45]  Matthias J. Müller,et al.  Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment , 2005, Neurobiology of Aging.

[46]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[47]  A. Burns.  Clinical diagnosis of Alzheimer's disease , 1991 .

[48]  R E Snyder,et al.  Changes in water diffusion due to Wallerian degeneration in peripheral nerve , 1996, Magnetic resonance in medicine.

[49]  T. J. Grabowski,et al.  Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia , 2007 .

[50]  Matthias J. Müller,et al.  Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study , 2004, Dementia and Geriatric Cognitive Disorders.