Download PDF
Semin Neurol 2019; 39(02): 188-199
DOI: 10.1055/s-0039-1678580
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuroimaging in Dementias

Sowmya Mahalingam
1   Department of Radiology of Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
,
Ming-Kai Chen
1   Department of Radiology of Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
29 March 2019 (online)

    Permissions and Reprints

Abstract

Dementia is a global health issue, the burden of which will worsen with an increasingly aging population. Alzheimer's disease (AD) is the most common dementia, with 50 to 60% of all dementias attributable to AD alone, while the rest are mostly due to frontotemporal lobar dementia, dementia with Lewy bodies, Parkinson's disease dementia, and vascular dementia. Diagnosis of dementias is made clinically with the aid of other testing modalities including neuroimaging. While the role of imaging has traditionally been to exclude reversible causes of dementia, positron emission tomography (PET) with 18-fluorine fluorodeoxyglucose and magnetic resonance imaging now are increasingly used more for definitive diagnosis of dementia in the prodromal stages and to aid with formulating the differential diagnoses. Introduction of molecular imaging modalities such as amyloid PET and tau PET have improved diagnostic certainty in the clinical trial setting and promise to find their way into the clinic in the near future. In this review, we will focus on the multimodality imaging of dementias especially AD and its differential diagnoses.

Keywords

dementia - Alzheimer's disease (AD) - magnetic resonance imaging (MRI) - positron emission tomography (PET) - fluorodeoxyglucose (FDG)
 

  • References

  • 1 Wortmann M. Dementia: a global health priority - highlights from an ADI and World Health Organization report. Alzheimers Res Ther 2012; 4 (05) 40
    CrossrefPubMedGoogle Scholar
  • 2 Brown RK, Bohnen NI, Wong KK, Minoshima S, Frey KA. Brain PET in suspected dementia: patterns of altered FDG metabolism. Radiographics. 2014; 34 (03) 684-701
    PubMedGoogle Scholar
  • 3 Scheltens P, Blennow K, Breteler MM. , et al. Alzheimer's disease. Lancet 2016; 388 (10043): 505-517
    CrossrefPubMedGoogle Scholar
  • 4 Jack Jr CR, Knopman DS, Weigand SD. , et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol 2012; 71 (06) 765-775
    CrossrefPubMedGoogle Scholar
  • 5 Jack Jr CR. Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology 2012; 263 (02) 344-361
    CrossrefPubMedGoogle Scholar
  • 6 Farias ST, Mungas D, Reed BR, Harvey D, DeCarli C. Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts. Arch Neurol 2009; 66 (09) 1151-1157
    PubMedGoogle Scholar
  • 7 Menendez-Gonzalez M, Calatayud MT, Blazquez-Menes B. Exacerbation of Lewy bodies dementia due to memantine. J Alzheimers Dis 2005; 8 (03) 289-291
    CrossrefPubMedGoogle Scholar
  • 8 Whitwell JL, Weigand SD, Shiung MM. , 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
    CrossrefPubMedGoogle Scholar
  • 9 Jack Jr CR, Knopman DS, Jagust WJ. , et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12 (02) 207-216
    CrossrefPubMedGoogle Scholar
  • 10 Villemagne VL, Chételat G. Neuroimaging biomarkers in Alzheimer's disease and other dementias. Ageing Res Rev 2016; 30: 4-16
    CrossrefPubMedGoogle Scholar
  • 11 Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82 (04) 239-259
    CrossrefPubMedGoogle Scholar
  • 12 Villemagne VL, Doré V, Bourgeat P. , et al. Aβ-amyloid and Tau imaging in dementia. Semin Nucl Med 2017; 47 (01) 75-88
    CrossrefPubMedGoogle Scholar
  • 13 Jack Jr CR, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron 2013; 80 (06) 1347-1358
    CrossrefPubMedGoogle Scholar
  • 14 Baron JC, Chételat G, Desgranges B. , et al. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease. Neuroimage 2001; 14 (02) 298-309
    CrossrefPubMedGoogle Scholar
  • 15 Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006; 129 (Pt 3): 564-583
    CrossrefPubMedGoogle Scholar
  • 16 Kobayashi Y. Neuroanatomy of the parietal association areas [in Japanese]. Brain Nerve 2016; 68 (11) 1301-1312
    PubMedGoogle Scholar
  • 17 Eichenbaum H, Yonelinas AP, Ranganath C. The medial temporal lobe and recognition memory. Annu Rev Neurosci 2007; 30 (01) 123-152
    CrossrefPubMedGoogle Scholar
  • 18 Jack Jr CR, Dickson DW, Parisi JE. , et al. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology 2002; 58 (05) 750-757
    CrossrefPubMedGoogle Scholar
  • 19 Jack Jr CR, Petersen RC, Xu Y. , et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology 1998; 51 (04) 993-999
    CrossrefPubMedGoogle Scholar
  • 20 Petersen RC, Jack Jr CR, Xu YC. , et al. Memory and MRI-based hippocampal volumes in aging and AD. Neurology 2000; 54 (03) 581-587
    CrossrefPubMedGoogle Scholar
  • 21 Shi F, Liu B, Zhou Y, Yu C, Jiang T. Hippocampal volume and asymmetry in mild cognitive impairment and Alzheimer's disease: meta-analyses of MRI studies. Hippocampus 2009; 19 (11) 1055-1064
    CrossrefPubMedGoogle Scholar
  • 22 Hashimoto M, Kitagaki H, Imamura T. , et al. Medial temporal and whole-brain atrophy in dementia with Lewy bodies: a volumetric MRI study. Neurology 1998; 51 (02) 357-362
    CrossrefPubMedGoogle Scholar
  • 23 Vemuri P, Simon G, Kantarci K. , et al. Antemortem differential diagnosis of dementia pathology using structural MRI: differential-STAND. Neuroimage 2011; 55 (02) 522-531
    CrossrefPubMedGoogle Scholar
  • 24 Greicius MD, Srivastava G, Reiss AL, 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 (13) 4637-4642
    CrossrefPubMedGoogle Scholar
  • 25 Yoshiura T, Hiwatashi A, Noguchi T. , et al. Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer's disease. Eur Radiol 2009; 19 (12) 2819-2825
    CrossrefPubMedGoogle Scholar
  • 26 Landau SM, Harvey D, Madison CM. , et al; Alzheimer's Disease Neuroimaging Initiative. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging 2011; 32 (07) 1207-1218
    CrossrefPubMedGoogle Scholar
  • 27 Bélanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 2011; 14 (06) 724-738
    CrossrefPubMedGoogle Scholar
  • 28 Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36 (07) 1238-1248
    PubMedGoogle Scholar
  • 29 Weiner MW, Aisen PS, Jack Jr CR. , et al; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's disease neuroimaging initiative: progress report and future plans. Alzheimers Dement 2010; 6 (03) 202-11.e7
    CrossrefPubMedGoogle Scholar
  • 30 Lehman VT, Carter RE, Claassen DO. , et al. Visual assessment versus quantitative three-dimensional stereotactic surface projection fluorodeoxyglucose positron emission tomography for detection of mild cognitive impairment and Alzheimer disease. Clin Nucl Med 2012; 37 (08) 721-726
    CrossrefPubMedGoogle Scholar
  • 31 Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 1997; 42 (01) 85-94
    CrossrefPubMedGoogle Scholar
  • 32 Garibotto V, Herholz K, Boccardi M. , et al; Geneva Task Force for the Roadmap of Alzheimer's Biomarkers. Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging 2017; 52: 183-195
    CrossrefPubMedGoogle Scholar
  • 33 Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005; 32 (04) 486-510
    CrossrefPubMedGoogle Scholar
  • 34 Kim EJ, Cho SS, Jeong Y. , et al. Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. Brain 2005; 128 (Pt 8): 1790-1801
    CrossrefPubMedGoogle Scholar
  • 35 Silverman DH, Small GW, Chang CY. , et al. Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 2001; 286 (17) 2120-2127
    CrossrefPubMedGoogle Scholar
  • 36 Bao W, Jia H, Finnema S, Cai Z, Carson RE, Huang YH. PET imaging for early detection of Alzheimer's disease: from pathologic to physiologic biomarkers. PET Clin 2017; 12 (03) 329-350
    CrossrefPubMedGoogle Scholar
  • 37 Sakamoto S, Ishii K, Sasaki M. , et al. Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease. J Neurol Sci 2002; 200 (1-2): 27-32
    CrossrefPubMedGoogle Scholar
  • 38 Shivamurthy VK, Tahari AK, Marcus C, Subramaniam RM. Brain FDG PET and the diagnosis of dementia. AJR Am J Roentgenol 2015; 204 (01) W76-85
    PubMedGoogle Scholar
  • 39 Elias A, Woodward M, Rowe CC. Management impact of FDG-PET in dementia: results from a tertiary center memory clinic. J Alzheimers Dis 2014; 42 (03) 885-892
    CrossrefPubMedGoogle Scholar
  • 40 Laforce Jr R, Buteau JP, Paquet N, Verret L, Houde M, Bouchard RW. The value of PET in mild cognitive impairment, typical and atypical/unclear dementias: a retrospective memory clinic study. Am J Alzheimers Dis Other Demen 2010; 25 (04) 324-332
    CrossrefPubMedGoogle Scholar
  • 41 Chételat G, Desgranges B, de la Sayette V, Viader F, Eustache F, Baron JC. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer's disease?. Neurology 2003; 60 (08) 1374-1377
    CrossrefPubMedGoogle Scholar
  • 42 de Leon MJ, Convit A, Wolf OT. , et al. Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A 2001; 98 (19) 10966-10971
    CrossrefPubMedGoogle Scholar
  • 43 Smailagic N, Vacante M, Hyde C, Martin S, Ukoumunne O, Sachpekidis C. 18F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2015; 1: CD010632
    CrossrefPubMedGoogle Scholar
  • 44 Morbelli S, Garibotto V, Van De Giessen E. , et al; European Association of Nuclear Medicine. A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives. Eur J Nucl Med Mol Imaging 2015; 42 (10) 1487-1491
    CrossrefPubMedGoogle Scholar
  • 45 Wiers CE, Shokri-Kojori E, Wong CT. , et al. Cannabis abusers show hypofrontality and blunted brain responses to a stimulant challenge in females but not in males. Neuropsychopharmacology 2016; 41 (10) 2596-2605
    CrossrefPubMedGoogle Scholar
  • 46 Ishibashi K, Onishi A, Fujiwara Y, Ishiwata K, Ishii K. Relationship between Alzheimer disease-like pattern of 18F-FDG and fasting plasma glucose levels in cognitively normal volunteers. J Nucl Med 2015; 56 (02) 229-233
    CrossrefPubMedGoogle Scholar
  • 47 Burns CM, Chen K, Kaszniak AW. , et al. Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions. Neurology 2013; 80 (17) 1557-1564
    CrossrefPubMedGoogle Scholar
  • 48 Teipel SJ, Drzezga A, Bartenstein P, Möller HJ, Schwaiger M, Hampel H. Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer's disease: a double-blind cross-over trial. Psychopharmacology (Berl) 2006; 187 (01) 86-94
    CrossrefPubMedGoogle Scholar
  • 49 Chen MK, Mecca AP, Naganawa M. , et al. Assessing synaptic density in Alzheimer disease with synaptic vesicle glycoprotein 2A positron emission tomographic imaging. JAMA Neurol 2018; 75 (10) 1215-1224
    CrossrefPubMedGoogle Scholar
  • 50 Klunk WE, Engler H, Nordberg A. , et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol 2004; 55 (03) 306-319
    CrossrefPubMedGoogle Scholar
  • 51 Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 2003; 46 (13) 2740-2754
    CrossrefPubMedGoogle Scholar
  • 52 Anand K, Sabbagh M. Amyloid imaging: poised for integration into medical practice. Neurotherapeutics 2017; 14 (01) 54-61
    CrossrefPubMedGoogle Scholar
  • 53 Clark CM, Pontecorvo MJ, Beach TG. , et al; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol 2012; 11 (08) 669-678
    CrossrefPubMedGoogle Scholar
  • 54 Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE. Amyloid imaging in Alzheimer's disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry 2012; 83 (09) 923-926
    CrossrefPubMedGoogle Scholar
  • 55 Joshi AD, Pontecorvo MJ, Lu M, Skovronsky DM, Mintun MA, Devous Sr MD. A semiautomated method for quantification of F 18 florbetapir PET images. J Nucl Med 2015; 56 (11) 1736-1741
    CrossrefPubMedGoogle Scholar
  • 56 Nayate AP, Dubroff JG, Schmitt JE. , et al; Alzheimer's Disease Neuroimaging Initiative. Use of standardized uptake value ratios decreases interreader variability of [18F] florbetapir PET brain scan interpretation. AJNR Am J Neuroradiol 2015; 36 (07) 1237-1244
    CrossrefPubMedGoogle Scholar
  • 57 Trembath L, Newell M, Devous Sr MD. Technical considerations in brain amyloid PET imaging with 18F-florbetapir. J Nucl Med Technol 2015; 43 (03) 175-184
    CrossrefPubMedGoogle Scholar
  • 58 Chételat G, La Joie R, Villain N. , et al. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. Neuroimage Clin 2013; 2: 356-365
    CrossrefPubMedGoogle Scholar
  • 59 Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease. Ann Neurol 1999; 45 (03) 358-368
    CrossrefPubMedGoogle Scholar
  • 60 Grundman M, Pontecorvo MJ, Salloway SP. , et al; 45-A17 Study Group. Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Alzheimer Dis Assoc Disord 2013; 27 (01) 4-15
    CrossrefPubMedGoogle Scholar
  • 61 Villemagne VL. Amyloid imaging: past, present and future perspectives. Ageing Res Rev 2016; 30: 95-106
    CrossrefPubMedGoogle Scholar
  • 62 Klunk WE, Koeppe RA, Price JC. , et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 2015; 11 (01) 1-15.e1 , 4
    PubMedGoogle Scholar
  • 63 Johnson KA, Minoshima S, Bohnen NI. , et al; Alzheimer's Association; Society of Nuclear Medicine and Molecular Imaging; Amyloid Imaging Taskforce. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association. Alzheimers Dement 2013; 9 (01) e-1-e-16
    CrossrefPubMedGoogle Scholar
  • 64 Cummings JL, Morstorf T, Zhong K. Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther 2014; 6 (04) 37
    CrossrefPubMedGoogle Scholar
  • 65 Villemagne VL, Okamura N. Tau imaging in the study of ageing, Alzheimer's disease, and other neurodegenerative conditions. Curr Opin Neurobiol 2016; 36: 43-51
    CrossrefPubMedGoogle Scholar
  • 66 Harada R, Okamura N, Furumoto S. , et al. Characteristics of tau and its ligands in PET imaging. Biomolecules 2016; 6 (01) 7
    CrossrefPubMedGoogle Scholar
  • 67 Holtzman DM, Carrillo MC, Hendrix JA. , et al. Tau: from research to clinical development. Alzheimers Dement 2016; 12 (10) 1033-1039
    CrossrefPubMedGoogle Scholar
  • 68 Ng KP, Pascoal TA, Mathotaarachchi S. , et al. Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain. Alzheimers Res Ther 2017; 9 (01) 25
    CrossrefPubMedGoogle Scholar
  • 69 Betthauser TJ, Cody KA, Zammit MD. , et al. In vivo characterization and quantification of neurofibrillary tau PET radioligand [18F]MK-6240 in humans from Alzheimer's disease dementia to young controls. J Nucl Med 2018; jnumed.118.209650
    PubMedGoogle Scholar
  • 70 Lohith TG, Bennacef I, Vandenberghe R. , et al. First-in-human brain imaging of Alzheimer dementia patients and elderly controls with 18F-MK-6240, a PET tracer targeting neurofibrillary tangle pathology. J Nucl Med 2018; jnumed.118.208215
    PubMedGoogle Scholar
  • 71 Pascoal TA, Shin M, Kang MS. , et al. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimers Res Ther 2018; 10 (01) 74
    CrossrefPubMedGoogle Scholar
  • 72 Kuwabara H, Comley RA, Borroni E. , et al. Evaluation of 18F-RO-948 PET for quantitative assessment of tau accumulation in the human brain. J Nucl Med 2018; 59 (12) 1877-1884
    CrossrefPubMedGoogle Scholar