Neuroimaging in Dementia

Paolo Vitali; Raffaella Migliaccio; Federica Agosta; Howard J. Rosen; Michael D. Geschwind

doi:10.1055/s-0028-1083695

Seminars in Neurology, Table of Contents

Semin Neurol 2008; 28(4): 467-483
DOI: 10.1055/s-0028-1083695

Neuroimaging in Dementia

Paolo Vitali¹ ^, ² , Raffaella Migliaccio¹ ^, ⁴ , Federica Agosta¹ ^, ³ , Howard J. Rosen¹ , Michael D. Geschwind¹

¹UCSF Department of Neurology, Memory and Aging Center, San Francisco, California
²Departments of Neurosurgery and Neuroradiology, Neurological Institute C. Besta, Milan, Italy
³Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Milan, Italy
⁴Second Division of Neurology, Second University of Naples, Naples, Italy

Abstract

ABSTRACT

Although dementia is a clinical diagnosis, neuroimaging often is crucial for proper assessment. Magnetic resonance imaging (MRI) and computed tomography (CT) may identify nondegenerative and potentially treatable causes of dementia. Recent neuroimaging advances, such as the Pittsburgh Compound-B (PIB) ligand for positron emission tomography imaging in Alzheimer's disease, will improve our ability to differentiate among the neurodegenerative dementias. High-resolution volumetric MRI has increased the capacity to identify the various forms of the frontotemporal lobar degeneration spectrum and some forms of parkinsonism or cerebellar neurodegenerative disorders, such as corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy, and spinocerebellar ataxias. In many cases, the specific pattern of cortical and subcortical abnormalities on MRI has diagnostic utility. Finally, among the new MRI methods, diffusion-weighted MRI can help in the early diagnosis of Creutzfeldt-Jakob disease. Although only clinical assessment can lead to a diagnosis of dementia, neuroimaging is clearly an invaluable tool for the clinician in the differential diagnosis.

KEYWORDS

MRI - PET - Pittsburgh Compound-B - dementia - neurodegenerative disease

Full Text

References

REFERENCES

1 Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 1991; 82 239-259
2 Maurer K, Volk S, Gerbaldo H. Auguste D and Alzheimer's disease. Lancet. 1997; 349 1546-1549
3 Klunemann H H, Fronhofer W, Wurster H, Fischer W, Ibach B, Klein H E. Alzheimer's second patient: Johann F and his family. Ann Neurol. 2002; 52 520-523
4 Ishii K, Kawachi T, Sasaki H et al.. Voxel-based morphometric comparison between early- and late-onset mild Alzheimer's disease and assessment of diagnostic performance of z score images. AJNR Am J Neuroradiol. 2005; 26 333-340
5 Karas G, Scheltens P, Rombouts S et al.. Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study. Neuroradiology. 2007; 49 967-976
6 Frisoni G B, Pievani M, Testa C et al.. The topography of grey matter involvement in early and late onset Alzheimer's disease. Brain. 2007; 130(Pt 3) 720-730
7 Krasuski J S, Alexander G E, Horwitz B et al.. Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biol Psychiatry. 1998; 43 60-68
8 Rusinek H, de Leon M J, George A E et al.. Alzheimer disease: measuring loss of cerebral gray matter with MR imaging. Radiology. 1991; 178 109-114
9 Teipel S J, Bayer W, Alexander G E et al.. Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration. Neurobiol Aging. 2003; 24 85-94
10 Tomaiuolo F, Scapin M, Di Paola M et al.. Gross anatomy of the corpus callosum in Alzheimer's disease: regions of degeneration and their neuropsychological correlates. Dement Geriatr Cogn Disord. 2007; 23 96-103
11 Zhang Y, Schuff N, Jahng G H et al.. Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology. 2007; 68 13-19
12 Yamauchi H, Fukuyama H, Nagahama Y et al.. Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2000; 69 623-629
13 Likeman M, Anderson V M, Stevens J M et al.. Visual assessment of atrophy on magnetic resonance imaging in the diagnosis of pathologically confirmed young-onset dementias. Arch Neurol. 2005; 62 1410-1415
14 Scheltens P, Fox N, Barkhof F, De Carli C. Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion. Lancet Neurol. 2002; 1 13-21
15 Minoshima S, Giordani B, Berent S, Frey K A, Foster N L, Kuhl D E. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997; 42 85-94
16 Ishii K, Sakamoto S, Sasaki M et al.. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med. 1998; 39 1875-1878
17 Herholz K. PET studies in dementia. Ann Nucl Med. 2003; 17 79-89
18 Choo I H, Lee D Y, Youn J C et al.. Topographic patterns of brain functional impairment progression according to clinical severity staging in 116 Alzheimer disease patients: FDG-PET study. Alzheimer Dis Assoc Disord. 2007; 21 77-84
19 Hoffman J M, Welsh-Bohmer K A, Hanson M et al.. FDG-PET imaging in patients with pathologically verified dementia. J Nucl Med. 2000; 41 1920-1928
20 Jagust W, Reed B, Mungas D, Ellis W, Decarli C. What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia?. Neurology. 2007; 69 871-877
21 Jagust W, Thisted R, Devous Sr M D et al.. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study. Neurology. 2001; 56 950-956
22 Sandson T A, O'Connor M, Sperling R A, Edelman R R, Warach S. Noninvasive perfusion MRI in Alzheimer's disease: a preliminary report. Neurology. 1996; 47 1339-1342
23 Bozzao A, Floris R, Baviera M E, Apruzzese A, Simonetti G. Diffusion and perfusion MR imaging in cases of Alzheimer's disease: correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol. 2001; 22 1030-1036
24 Rabinovici G D, Furst A J, O'Neil J P et al.. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007; 68 1205-1212
25 Petersen R C, Doody R, Kurz A et al.. Current concepts in mild cognitive impairment. Arch Neurol. 2001; 58 1985-1992
26 Chetelat G, Landeau B, Eustache F et al.. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage. 2005; 27 934-946
27 DeCarli C, Frisoni G B, Clark C M et al.. Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol. 2007; 64 108-115
28 Chetelat G, Desgranges B, de la Sayette V, Viader F, Eustache F, Baron J C. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer's disease?. Neurology. 2003; 60 1374-1377
29 Mosconi L, Perani D, Sorbi S et al.. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology. 2004; 63 2332-2340
30 Anchisi D, Borroni B, Franceschi M et al.. Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. Arch Neurol. 2005; 62 1728-1733
31 Hirao K, Ohnishi T, Hirata Y et al.. The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT. Neuroimage. 2005; 28 1014-1021
32 Kemppainen N M, Aalto S, Wilson I A et al.. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology. 2007; 68 1603-1606
33 Johnson J K, Diehl J, Mendez M F et al.. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol. 2005; 62 925-930
34 Ratnavalli E, Brayne C, Dawson K, Hodges J R. The prevalence of frontotemporal dementia. Neurology. 2002; 58 1615-1621
35 Rosso S M, Donker Kaat L, Baks T et al.. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003; 126(Pt 9) 2016-2022
36 Neary D, Snowden J S, Gustafson L et al.. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998; 51 1546-1554
37 Rosen H J, Gorno-Tempini M L, Goldman W P et al.. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology. 2002; 58 198-208
38 Rosen H J, Kramer J H, Gorno-Tempini M L, Schuff N, Weiner M, Miller B L. Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry. 2002; 10 89-97
39 Gorno-Tempini M L, Dronkers N F, Rankin K P et al.. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004; 55 335-346
40 Neary D, Snowden J S, Mann D M. Classification and description of frontotemporal dementias. Ann N Y Acad Sci. 2000; 920(51–52) 46-51
41 Kril J J, Halliday G M. Clinicopathological staging of frontotemporal dementia severity: correlation with regional atrophy. Dement Geriatr Cogn Disord. 2004; 17 311-315
42 Miller B L, Gearhart R. Neuroimaging in the diagnosis of frontotemporal dementia. Dement Geriatr Cogn Disord. 1999; 10(S1) 71-74
43 Kipps C M, Davies R R, Mitchell J, Kril J J, Halliday G M, Hodges J R. Clinical significance of lobar atrophy in frontotemporal dementia: application of an MRI visual rating scale. Dement Geriatr Cogn Disord. 2007; 23 334-342
44 Kitagaki H, Mori E, Yamaji S et al.. Frontotemporal dementia and Alzheimer disease: evaluation of cortical atrophy with automated hemispheric surface display generated with MR images. Radiology. 1998; 208 431-439
45 Frisoni G B, Beltramello A, Geroldi C, Weiss C, Bianchetti A, Trabucchi M. Brain atrophy in frontotemporal dementia. J Neurol Neurosurg Psychiatry. 1996; 61 157-165
46 Chan D, Fox N C, Scahill R I et al.. Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease. Ann Neurol. 2001; 49 433-442
47 Galton C J, Gomez-Anson B, Antoun N et al.. Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2001; 70 165-173
48 Mummery C J, Patterson K, Price C J, Ashburner J, Frackowiak R S, Hodges J. A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol. 2000; 47 36-45
49 Whitwell J L, Josephs K A, Rossor M N et al.. Magnetic resonance imaging signatures of tissue pathology in frontotemporal dementia. Arch Neurol. 2005; 62 1402-1408
50 Rabinovici G D, Seeley W W, Kim E J et al.. Distinct MRI atrophy patterns in autopsy-proven Alzheimer's disease and frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen. 2007; 22 474-488
51 Fukui T, Kertesz A. Volumetric study of lobar atrophy in Pick complex and Alzheimer's disease. J Neurol Sci. 2000; 174 111-121
52 Barnes J, Whitwell J L, Frost C, Josephs K A, Rossor M, Fox N C. Measurements of the amygdala and hippocampus in pathologically confirmed Alzheimer disease and frontotemporal lobar degeneration. Arch Neurol. 2006; 63 1434-1439
53 Du A T, Schuff N, Kramer J H et al.. Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia. Brain. 2007; 130(Pt 4) 1159-1166
54 Johnson J K, Head E, Kim R, Starr A, Cotman C W. Clinical and pathological evidence for a frontal variant of Alzheimer disease. Arch Neurol. 1999; 56 1233-1239
55 Varma A R, Snowden J S, Lloyd J J, Talbot P R, Mann D M, Neary D. Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer's disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry. 1999; 66 184-188
56 Talbot P R, Lloyd J J, Snowden J S, Neary D, Testa H J. A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?. J Neurol Neurosurg Psychiatry. 1998; 64 306-313
57 Foster N L, Heidebrink J L, Clark C M et al.. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain. 2007; 130(Pt 10) 2616-2635
58 Nestor P J, Graham N L, Fryer T D, Williams G B, Patterson K, Hodges J R. Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain. 2003; 126(Pt 11) 2406-2418
59 Diehl-Schmid J, Grimmer T, Drzezga A et al.. Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol Aging. 2007; 28 42-50
60 Du A T, Jahng G H, Hayasaka S et al.. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology. 2006; 67 1215-1220
61 Jellinger K A. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 2007; 113 349-388
62 Pohjasvaara T, Mantyla R, Ylikoski R, Kaste M, Erkinjuntti T. Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. National Institute of Neurological Disorders and Stroke—Association Internationale pour la Recherche et l'Enseignement en Neurosciences. Stroke. 2000; 31 2952-2957
63 Hachinski V C, Illiff L D, Zilhka E, du Boulay G H, McAllister V L, Marchall J. Cerebral blood flow in dementia. Arch Neurol. 1975; 32 632-637
64 Vermeer S E, Longstreth Jr W T, Koudstaal P J. Silent brain infarcts: a systematic review. Lancet Neurol. 2007; 6 611-619
65 Staekenborg S S, van der Flier W M, van Straaten E C, Lane R, Barkhof F, Scheltens P. Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke. 2008; 39 317-322
66 Johnston S C, O'Meara E S, Manolio T A et al.. Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med. 2004; 140 237-247
67 Berman L, Pietrzak R H, Mayes L. Neurocognitive changes after carotid revascularization: a review of the current literature. J Psychosom Res. 2007; 63 599-612
68 Mlekusch W, Mlekusch I, Haumer M et al.. Improvement of neurocognitive function after protected carotid artery stenting. Catheter Cardiovasc Interv. 2008; 71 114-119
69 Turk A S, Chaudry I, Haughton V M et al.. Effect of carotid artery stenting on cognitive function in patients with carotid artery stenosis: preliminary results. AJNR Am J Neuroradiol. 2008; 29 265-268
70 Leys D, Henon H, Mackowiak-Cordoliani M A, Pasquier F. Poststroke dementia. Lancet Neurol. 2005; 4 752-759
71 Guermazi A, Miaux Y, Rovira-Canellas A et al.. Neuroradiological findings in vascular dementia. Neuroradiology. 2007; 49 1-22
72 Pohjasvaara T, Mantyla R, Salonen O et al.. MRI correlates of dementia after first clinical ischemic stroke. J Neurol Sci. 2000; 181(1–2) 111-117
73 Auchus A P, Chen C P, Sodagar S N, Thong M, Sng E C. Single stroke dementia: insights from 12 cases in Singapore. J Neurol Sci. 2002; 203–204 85-89
74 Roman G C, Erkinjuntti T, Wallin A, Pantoni L, Chui H C. Subcortical ischaemic vascular dementia. Lancet Neurol. 2002; 1 426-436
75 Kumral E, Evyapan D, Balkir K. Acute caudate vascular lesions. Stroke. 1999; 30 100-108
76 Mizuta H, Motomura N. Memory dysfunction in caudate infarction caused by Heubner's recurring artery occlusion. Brain Cogn. 2006; 61 133-138
77 Carrera E, Bogousslavsky J. The thalamus and behavior: effects of anatomically distinct strokes. Neurology. 2006; 66 1817-1823
78 Shim Y S, Kim J S, Shon Y M, Chung Y A, Ahn K J, Yang D W. A serial study of regional cerebral blood flow deficits in patients with left anterior thalamic infarction: anatomical and neuropsychological correlates. J Neurol Sci. 2008; 266(1–2) 84-91
79 Hachinski V C, Potter P, Merskey H. Leuko-araiosis. Arch Neurol. 1987; 44 21-23
80 Roman G C. Senile dementia of the Binswanger type. A vascular form of dementia in the elderly. JAMA. 1987; 258 1782-1788
81 Boone K B, Miller B L, Lesser I M et al.. Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol. 1992; 49 549-554
82 van Straaten E C, Scheltens P, Knol D L et al.. Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study. Stroke. 2003; 34 1907-1912
83 Kramer J H, Mungas D, Reed B R et al.. Forgetting in dementia with and without subcortical lacunes. Clin Neuropsychol. 2004; 18 32-40
84 Mungas D, Harvey D, Reed B R et al.. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology. 2005; 65 565-571
85 Au R, Massaro J M, Wolf P A et al.. Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. Arch Neurol. 2006; 63 246-250
86 Carey C L, Woods S P, Damon J et al.. Discriminant validity and neuroanatomical correlates of rule monitoring in frontotemporal dementia and Alzheimer's disease. Neuropsychologia. 2008; 46 1081-1087
87 Debette S, Bombois S, Bruandet A et al.. Subcortical hyperintensities are associated with cognitive decline in patients with mild cognitive impairment. Stroke. 2007; 38 2924-2930
88 Yong S W, Bang O Y, Lee P H, Li W Y. Internal and cortical border-zone infarction: clinical and diffusion-weighted imaging features. Stroke. 2006; 37 841-846
89 Kuker W. Cerebral vasculitis: imaging signs revisited. Neuroradiology. 2007; 49 471-479
90 Chabriat H, Levy C, Taillia H et al.. Patterns of MRI lesions in CADASIL. Neurology. 1998; 51 452-457
91 Josephson S A, Papanastassiou A M, Berger M S et al.. The diagnostic utility of brain biopsy procedures in patients with rapidly deteriorating neurological conditions or dementia. J Neurosurg. 2007; 106 72-75
92 Liem M K, van der Grond J, Haan J et al.. Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL. Stroke. 2007; 38 923-928
93 Viswanathan A, Gschwendtner A, Guichard J P et al.. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology. 2007; 69 172-179
94 Cordonnier C, van der Flier W M, Sluimer J D, Leys D, Barkhof F, Scheltens P. Prevalence and severity of microbleeds in a memory clinic setting. Neurology. 2006; 66 1356-1360
95 Koennecke H C. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology. 2006; 66 165-171
96 Lee S H, Kim S M, Kim N, Yoon B W, Roh J K. Cortico-subcortical distribution of microbleeds is different between hypertension and cerebral amyloid angiopathy. J Neurol Sci. 2007; 258(1–2) 111-114
97 Hachinski V, Iadecola C, Petersen R C et al.. National Institute of Neurological Disorders and Stroke–Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006; 37 2220-2241
98 Tzourio C, Anderson C, Chapman N et al.. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003; 163 1069-1075
99 Shlyakhto E. Observational Study on Cognitive Function and Systolic Blood Pressure Reduction (OSCAR): preliminary analysis of 6-month data from >10,000 patients and review of the literature. Curr Med Res Opin. 2007; 23(S5) S13-S18
100 Weisman D, McKeith I. Dementia with Lewy bodies. Semin Neurol. 2007; 27 42-47
101 Burton E J, Karas G, Paling S M et al.. Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry. Neuroimage. 2002; 17 618-630
102 Brenneis C, Wenning G K, Egger K E et al.. Basal forebrain atrophy is a distinctive pattern in dementia with Lewy bodies. Neuroreport. 2004; 15 1711-1714
103 Whitwell J L, Weigand S D, Shiung M M et al.. Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease. Brain. 2007; 130(Pt 3) 708-719
104 Cousins D A, Burton E J, Burn D, Gholkar A, McKeith I G, O'Brien J T. Atrophy of the putamen in dementia with Lewy bodies but not Alzheimer's disease: an MRI study. Neurology. 2003; 61 1191-1195
105 McKeith I, O'Brien J, Walker Z et al.. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007; 6 305-313
106 Berg D. Disturbance of iron metabolism as a contributing factor to SN hyperechogenicity in Parkinson's disease: implications for idiopathic and monogenetic forms. Neurochem Res. 2007; 32 1646-1654
107 Walter U, Dressler D, Probst T et al.. Transcranial brain sonography findings in discriminating between parkinsonism and idiopathic Parkinson disease. Arch Neurol. 2007; 64 1635-1640
108 Litvan I, Agid Y, Goetz C et al.. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology. 1997; 48 119-125
109 Soliveri P, Monza D, Paridi D et al.. Cognitive and magnetic resonance imaging aspects of corticobasal degeneration and progressive supranuclear palsy. Neurology. 1999; 53 502-507
110 Boxer A L, Geschwind M D, Belfor N et al.. Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol. 2006; 63 81-86
111 Litvan I, Agid Y, Jankovic J et al.. Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology. 1996; 46 922-930
112 Warmuth-Metz M, Naumann M, Csoti I, Solymosi L. Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol. 2001; 58 1076-1079
113 Oba H, Yagishita A, Terada H et al.. New and reliable MRI diagnosis for progressive supranuclear palsy. Neurology. 2005; 64 2050-2055
114 Quattrone A, Nicoletti G, Messina D et al.. MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology. 2008; 246 214-221
115 Schwarz J, Weis S, Kraft E et al.. Signal changes on MRI and increases in reactive microgliosis, astrogliosis, and iron in the putamen of two patients with multiple system atrophy. J Neurol Neurosurg Psychiatry. 1996; 60 98-101
116 von Lewinski F, Werner C, Jorn T, Mohr A, Sixel-Doring F, Trenkwalder C. T2*-weighted MRI in diagnosis of multiple system atrophy. A practical approach for clinicians. J Neurol. 2007; 254 1184-1188
117 Savoiardo M. Differential diagnosis of Parkinson's disease and atypical parkinsonian disorders by magnetic resonance imaging. Neurol Sci. 2003; 24(S1) S35-S37
118 Burk K, Daum I, Rub U. Cognitive function in multiple system atrophy of the cerebellar type. Mov Disord. 2006; 21 772-776
119 Abe K, Hikita T, Yokoe M, Mihara M, Sakoda S. The “cross” signs in patients with multiple system atrophy: a quantitative study. J Neuroimaging. 2006; 16 73-77
120 Burk K, Buhring U, Schulz J B, Zuhlke C, Hellenbroich Y, Dichgans J. Clinical and magnetic resonance imaging characteristics of sporadic cerebellar ataxia. Arch Neurol. 2005; 62 981-985
121 Mandelli M L, De Simone T, Minati L et al.. Diffusion tensor imaging of spinocerebellar ataxias types 1 and 2. AJNR Am J Neuroradiol. 2007; 28 1996-2000
122 Peterson K, Rosenblum M, Kotanides H, Posner J. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology. 1992; 42 1931-1937
123 Chang C C, Eggers S D, Johnson J K, Haman A, Miller B L, Geschwind M D. Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease. Clin Neurol Neurosurg. 2007; 109 54-57
124 Burk K. Cognition in hereditary ataxia. Cerebellum. 2007; 6 280-286
125 Klockgether T, Skalej M, Wedekind D et al.. Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3. Brain. 1998; 121(Pt 9) 1687-1693
126 Brenneis C, Bosch S M, Schocke M, Wenning G K, Poewe W. Atrophy pattern in SCA2 determined by voxel-based morphometry. Neuroreport. 2003; 14 1799-1802
127 Mariotti C, Alpini D, Fancellu R et al.. Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients. J Neurol. 2007; 254 1538-1546
128 Lin I S, Wu R M, Lee-Chen G J, Shan D E, Gwinn-Hardy K. The SCA17 phenotype can include features of MSA-C, PSP and cognitive impairment. Parkinsonism Relat Disord. 2007; 13 246-249
129 Loy C T, Sweeney M G, Davis M B et al.. Spinocerebellar ataxia type 17: extension of phenotype with putaminal rim hyperintensity on magnetic resonance imaging. Mov Disord. 2005; 20 1521-1523
130 Young G S, Geschwind M D, Fischbein N J et al.. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: high sensitivity and specificity for diagnosis. AJNR Am J Neuroradiol. 2005; 26 1551-1562
131 Shiga Y, Miyazawa K, Sato S et al.. Diffusion-weighted MRI abnormalities as an early diagnostic marker for Creutzfeldt-Jakob disease. Neurology. 2004; 63 443-449
132 Collie D A, Sellar R J, Zeidler M, Colchester C F, Knight R, Will R G. MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol. Clin Radiol. 2001; 56 726-739
133 Zeidler M, Sellar R J, Collie D A et al.. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet. 2000; 355 1412-1418
134 Lin Y R, Young G S, Chen N K, Dillon W P, Wong S. Creutzfeldt-Jakob disease involvement of rolandic cortex: a quantitative apparent diffusion coefficient evaluation. AJNR Am J Neuroradiol. 2006; 27 1755-1759
135 Boxer A L, Rabinovici G D, Kepe V et al.. Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease. Neurology. 2007; 69 283-290
136 Chu K, Kang D W, Kim H J, Lee Y S, Park S H. Diffusion-weighted imaging abnormalities in Wernicke's encephalopathy: reversible cytotoxic edema?. Arch Neurol. 2002; 59 123-127
137 Sener R N. Diffusion MRI findings in Wilson's disease. Comput Med Imaging Graph. 2003; 27 17-21
138 Singhal A B, Newstein M C, Budzik R et al.. Diffusion-weighted magnetic resonance imaging abnormalities in Bartonella encephalopathy. J Neuroimaging. 2003; 13 79-82
139 Josephs K A, Holton J L, Rossor M N et al.. Neurofilament inclusion body disease: a new proteinopathy?. Brain. 2003; 126(Pt 10) 2291-2303
140 Mihara M, Sugase S, Konaka K et al.. The “pulvinar sign” in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin's lymphoma. J Neurol Neurosurg Psychiatry. 2005; 76 882-884
141 Chu K, Kang D W, Kim J Y, Chang K H, Lee S K. Diffusion-weighted magnetic resonance imaging in nonconvulsive status epilepticus. Arch Neurol. 2001; 58 993-998
142 Hufnagel A, Weber J, Marks S et al.. Brain diffusion after single seizures. Epilepsia. 2003; 44 54-63
143 Vernino S, Geschwind M D, Boeve B. Autoimmune encephalopathies. Neurologist. 2007; 13 140-147
144 Vincent A, Buckley C, Schott J M et al.. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004; 127(Pt 3) 701-712
145 Geschwind M D, Yoon G, Goldman J. Adult onset genetic disorders involving the frontal lobes. In: Miller BL The Human Frontal Lobes: Functions and Disorders. New York, NY; The Guilford Press 2007: 552-575
146 Geschwind M D, Haman A, Miller B L. Rapidly progressive dementia. Neurol Clin. 2007; 25 783-807
147 Burdette J H, Elster A D, Ricci P E. Acute cerebral infarction: quantification of spin-density and T2 shine-through phenomena on diffusion-weighted MR images. Radiology. 1999; 212 333-339
148 Minati L, Grisoli M, Bruzzone M G. MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review. J Geriatr Psychiatry Neurol. 2007; 20 3-21
149 Paviour D C, Thornton J S, Lees A J, Jager H R. Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy. Mov Disord. 2007; 22 68-74
150 Vitali P, Henry R G, Chung S et al.. ADC measurements at the gyral level and of deep nuclei in sporadic Jakob-Creutzfeldt disease. LP03:18:6. Presented at 32nd Congress of the European Society of Neuroradiology. Genoa, Italy. Neuroradiology. 2007; 49(suppl 2) S149
151 Kantarci K, Petersen R C, Boeve B F et al.. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2005; 64 902-904
152 Stankiewicz J, Panter S S, Neema M, Arora A, Batt C E, Bakshi R. Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics. 2007; 4 371-386
153 Schenck J F, Zimmerman E A, Li Z et al.. High-field magnetic resonance imaging of brain iron in Alzheimer disease. Top Magn Reson Imaging. 2006; 17 41-50
154 Thomas B, Somasundaram S, Thamburaj K et al.. Clinical applications of susceptibility weighted MR imaging of the brain—a pictorial review. Neuroradiology. 2008; 50 105-116
155 Hayasaka S, Du A T, Duarte A et al.. A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer's disease. Neuroimage. 2006; 30 768-779
156 Logothetis N K, Pfeuffer J. On the nature of the BOLD fMRI contrast mechanism. Magn Reson Imaging. 2004; 22 1517-1531
157 Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann N Y Acad Sci. 2007; 1097 146-155
158 Greicius M D, Srivastava G, Reiss A L, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004; 101 4637-4642

Michael D GeschwindM.D. Ph.D.

University of California, San Francisco (UCSF), UCSF Memory and Aging Center

Box 1207, San Francisco, CA 94143-1207

Email: michael.geschwind@ucsf.edu