Reference
Reference
Study Type
Study Type
Patients/Events
Patients/Events
Study Objective(Purpose of Study)
Study Objective(Purpose of Study)
Study Results
Study Results
Study Quality
Study Quality
1. Imbimbo BP, Lombard J, Pomara N. Pathophysiology of Alzheimer's disease. Neuroimaging Clin N Am. 2005;15(4):727-753, ix. Review/Other-Dx N/A To review the basic knowledge of the pathophysiology of AD. Progress in understanding the cellular and molecular alterations that are responsible for the neuron’s death may help significantly in developing more effective medications to slow the progression of this devastating disease. Understanding cerebral degeneration and accumulation of ß-amyloid has generated hopes for discovery of disease-modifying treatments. Progress is needed in understanding the mechanisms that link (ß-amyloid) accumulation and neuronal death. 4
2. Wippold FJ, 2nd, Cairns N, Vo K, Holtzman DM, Morris JC. Neuropathology for the neuroradiologist: plaques and tangles. AJNR Am J Neuroradiol. 2008;29(1):18-22. Review/Other-Dx N/A To review the significance of plaques and neurofibrillary tangles in the context of AD. ß-amyloid plaques and neurofibrillary tangles are the histopathologic hallmarks of AD. Plaques are predominately composed of ß-amyloid peptide with frequently associated dystrophic neurites and inflammation. Neurofibrillary tangles are intracellular inclusions comprising hyperphosphorylated protein that disrupts normal microtubular function. Although the precise pathogenesis of AD is unknown, the burden of these 2 inclusions tends to increase with advancing dementia. Alzheimer’s original contribution to the neurosciences resides in his recognition of these 2 structures as pathologic manifestations of a neurodegenerative disorder, rather than the normal and expected culmination of aging. 4
3. Jack CR, Jr., Dickson DW, Parisi JE, et al. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002;58(5):750-757. Observational-Dx 67 patients To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. Individuals with frontotemporal degeneration usually had substantial hippocampal atrophy. Among all 67 subjects, correlations (all P<0.001) were observed between hippocampal volume and Braak and Braak stage (r = –0.39), between hippocampal volume and Mini-Mental State Examination score (r = 0.60), and between Mini-Mental State Examination score and Braak and Braak stage (r = –0.41). Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = –0.63, P=0.001]) and consequent cognitive status. 2
4. Jack CR, Jr., Shiung MM, Gunter JL, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology. 2004;62(4):591-600. Observational-Dx 160 total: 55 normal; 41 MCI; 64 AD To correlate different methods of measuring rates of brain atrophy from serial MRI with corresponding clinical change in normal elderly subjects, patients with MCI, and patients with PAD. All 4 atrophy rates were greater among normal subjects who converted to MCI or AD than among those who remained stable, greater among MCI subjects who converted to AD than among those who remained stable, and greater among fast than slow AD progressors. Atrophy on MRI was detected more consistently than decline on specific cognitive tests/rating scales. No differences were found among the 4 MRI rate measures in the strength of the correlation with clinical deterioration at different stages of the disease. These data support the use of rates of change from serial MRI studies in addition to standard clinical/psychometric measures as surrogate markers of disease progression in AD. Estimated sample sizes required to power a therapeutic trial in MCI were an order of magnitude less for MRI than for change measures based on cognitive tests/rating scales. 2
5. Keyserling H, Mukundan S, Jr. The role of conventional MR and CT in the work-up of dementia patients. Neuroimaging Clin N Am. 2005;15(4):789-802, x. Review/Other-Dx N/A To review the different types of dementia and their appearance on conventional CT and MRI studies. There often is overlap in the clinical manifestations of various forms of dementia, making them difficult to categorize. Neuroimaging can play an important role in distinguishing one form of dementia from another. Conventional MRI and CT can still contribute useful information when interpreting radiologists are familiar with the patterns of volume loss and signal or density changes that are characteristic of various forms of dementia. 4
6. Krishnan S, Talley BD, Slavin MJ, Doraiswamy PM, Petrella JR. Current status of functional MR imaging, perfusion-weighted imaging, and diffusion-tensor imaging in Alzheimer's disease diagnosis and research. Neuroimaging Clin N Am. 2005;15(4):853-868, xi. Review/Other-Dx N/A To describe pertinent studies applying fMRI, PWI, and DTI to the study of AD. Advanced MR techniques, such as fMRI, PWI, and DTI, offer the capability of detecting early functional, hemodynamic, and microstructural alterations in AD before gross anatomic alterations. 4
7. Small GW. Diagnostic issues in dementia: neuroimaging as a surrogate marker of disease. J Geriatr Psychiatry Neurol. 2006;19(3):180-185. Review/Other-Dx N/A To describe findings regarding the use of neuroimaging and research in dementia. FDG-PET scanning provides a reasonably accurate determination of the cause of dementia early in its course. Combining PET or other imaging methods with other genetic risk data provides additional information that indicates subtle brain abnormalities even earlier in the course of age-related memory decline. 4
8. Simon DG, Lubin MF. Cost-effectiveness of computerized tomography and magnetic resonance imaging in dementia. Med Decis Making. 1985;5(3):335-354. Review/Other-Dx N/A (hypothetical cohorts) To assess the benefits and costs of routinely using CT to diagnose surgically treatable causes of dementia compared to a more selective strategy, using a decision-analytic model, for hypothetical cohorts at 60, 70, and 80 years of age. Routine CT could be expected to detect between 1,425 and 14,930 additional surgically treatable cases at an extra cost of between $0 and $49 million per 100,000 persons scanned. Replacing CT with MRI might yield an additional 70 to 150 cases of surgically treatable dementia, at an additional cost of $20-$30 million. Given current treatment limitations in dementia, it appears that, as a clinical tool, MRI will have little immediate health impact on this problem. 4
9. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet. 2006;367(9518):1262-1270. Review/Other-Dx N/A Review available data and offer an expert opinion on where MCI stands as a clinical entity. MCI can be regarded as a risk state for dementia, The amnestic subtype of MCI has a high risk of progression to AD. 4
10. Murray AD. Imaging Approaches for Dementia. AJNR Am J Neuroradiol. 2011;33(10):1836-1844. Review/Other-Dx N/A To review brain imaging approaches for dementia. Brain imaging has progressed from exclusion of rare treatable mass lesions to a specific antemortem diagnosis. MRI-derived hippocampal atrophy and white matter hyperintensities are regarded as imaging biomarkers of AD and CVD respectively. Abnormal FP-CIT SPECT or cardiac iodobenzamide SPECT is a useful supportive imaging feature in the diagnosis of DLB. Frontal and/or anterior temporal atrophy and anterior defects on molecular imaging with FDG-PET or perfusion SPECT are characteristic of FTDs. Whole-body FDG-PET may be helpful in patients with rapidly progressing "autoimmune dementias," and FLAIR and DWI are indicated in suspected CJD. A major role of imaging is in the development of new drugs and less costly biomarkers. 4
11. Sarazin M, de Souza LC, Lehericy S, Dubois B. Clinical and research diagnostic criteria for Alzheimer's disease. Neuroimaging Clin N Am. 2012;22(1):23-32,viii. Review/Other-Dx N/A To review the clinical and research diagnostic criteria for AD. No results stated in abstract. 4
12. Jack CR, Jr. Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology. 2012;263(2):344-361. Review/Other-Dx N/A To review the neurobiology of AD. No results stated in abstract. 4
13. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143-1153. Review/Other-Dx N/A Update of the 1994 practice parameter for the diagnosis of dementia in the elderly. Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy. 4
14. Mosconi L, Tsui WH, Herholz K, et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J Nucl Med. 2008;49(3):390-398. Observational-Dx 548: 110 normal; 114 MCI; 199 AD; 98 FTD To examine FDG-PET measures in the differential diagnosis of AD, FTD, and DLB from normal aging and from each other and the relation of disease-specific patterns to MCI. Standardized disease-specific PET patterns were developed that correctly classified 95% AD, 92% DLB, 94% FTD, and 94% normal. FDG-PET heterogeneity in MCI with nonmemory deficits ranged from absent hypometabolism to FTD and DLB PET patterns. Standardized automated analysis of FDG-PET scans may provide an objective and sensitive support to the clinical diagnosis in early dementia. 3
15. 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(12):2332-2340. Observational-Dx 37 MCI patients To investigate whether the combination of FDG-PET measures with the APOE genotype would improve prediction of the conversion from MCI to AD. All converters showed reduced regional glucose metabolic rate in the inferior parietal cortex as compared with the nonconverters. 3
16. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306-319. Observational-Dx 25: 16 with mild AD; 9 controls Human study of an amyloid-imaging PET tracer, termed PIB, in patients with diagnosed mild AD compared to controls. PET imaging with PIB, can provide quantitative information on amyloid deposits in living subjects. 3
17. Okello A, Koivunen J, Edison P, et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73(10):754-760. Observational-Dx 31 subjects To assess the rates of conversion of MCI to AD during a 3-year follow-up period and to compare levels of amyloid deposition between MCI converters and nonconverters. 17/31 (55%) subjects with MCI had increased (11)C-PIB retention at baseline and 14/17 (82%) clinically converted to AD during follow-up. Only one of the 14 PIB-negative MCI cases converted to AD. Of the PIB-positive subjects with MCI, half (47%) converted to AD within 1 year of baseline PIB PET, these faster converters having higher tracer-retention values than slower converters in the anterior cingulate (P=0.027) and frontal cortex (P=0.031). 7/17 (41%) subjects with MCI with known APOE status were epsilon4 allele carriers, this genotype being associated with faster conversion rates in PIB-positive subjects with MCI (P=0.035). 3
18. Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275-283. Observational-Dx 152 patients To determine if florbetapir-PET imaging performed during life accurately predicts the presence of beta-amyloid in the brain at autopsy. Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. 15/29 individuals (51.7%) met pathological criteria for AD. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of beta-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni rho, 0.78 [95% confidence interval, 0.58-0.89]; P<.001]) and silver stain neuritic plaque score (Bonferroni rho, 0.71 [95% confidence interval, 0.47-0.86]; P<.001). Florbetapir-PET images and postmortem results rated as positive or negative for beta-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort. 2
19. Joshi AD, Pontecorvo MJ, Clark CM, et al. Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer's disease and cognitively normal subjects. J Nucl Med. 2012;53(3):378-384. Observational-Dx 20 patients in test-retest group; 20 patients in dose comparison patients To examine the effective dose range and the test-retest reliability of florbetapir F 18 using, first, visual assessment by independent raters masked to clinical information and, second, semiautomated quantitative measures of cortical target area to cerebellum standardized uptake value ratios as primary outcome measures. There were no meaningful differences between the 111-MBq (3-mCi) and 370-MBq (10-mCi) dose in the visual rating or standardized uptake value ratios. The difference in the visual quality across 111 and 370 MBq showed a trend toward lower image quality, but no statistical significance was achieved (t test; t(1) = -1.617, P=0.12) in this relatively small sample of subjects. At both dose levels, visual ratings of amyloid burden identified 100% of AD subjects as Abeta-positive and 100% of YHCs as Abeta-negative. Mean intrasubject test-retest variability for cortical average standardized uptake value ratios with the cerebellum as a reference over the 50- to 70-min period was 2.4% +/- 1.41% for AD subjects and 1.5% +/- 0.84% for controls. The overall standardized uptake value ratios test-retest correlation coefficient was 0.99. The overall kappa-statistic for test-retest agreement for Abeta classification of the masked reads was 0.89 (95% confidence interval, 0.69-1.0). 2
20. Wong DF, Rosenberg PB, Zhou Y, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med. 2010;51(6):913-920. Observational-Dx 16 patients; 16 controls To present the results of a clinical trial with 18F-AV-45 (florbetapir [corrected] F 18). Valid PET data were available for 11 AD patients and 15 healthy controls. 18F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (eg, precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of healthy controls. The cortical-to-cerebellar standardized uptake value ratios in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average standardized uptake value ratio for this period was 1.67 +/- 0.175 for patients with AD vs 1.25 +/- 0.177 for healthy controls. Spatially normalized distribution volume ratios generated from PET dynamic scans were highly correlated with standardized uptake value ratio (r = 0.58-0.88, P<0.005) and were significantly greater for AD patients than for healthy controls in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed. 3
21. Vandenberghe R, Van Laere K, Ivanoiu A, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68(3):319-329. Experimental-Dx 27 patients with early-stage clinically probable AD, 20 with amnestic MCI, and 25 controls. To assess the efficacy of blinded visual assessments of (18)F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for (18)F-flutemetamol and its parent molecule (11)C-PIB in 20 of the AD subjects and 20 of the MCI patients. Blinded visual assessments of (18)F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical (18)F-flutemetamol SUVRs and (11)C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. 1
22. Villemagne VL, Ong K, Mulligan RS, et al. Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011;52(8):1210-1217. Observational-Dx 109 subjects To compare cortical amyloid deposition using (18)F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD). When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P < 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical (18)F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and beta-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD. 2
23. Burack MA, Hartlein J, Flores HP, Taylor-Reinwald L, Perlmutter JS, Cairns NJ. In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology. 2010;74(1):77-84. Review/Other-Dx 3 cases To investigate the specificity of in vivo amyloid imaging with PIB in Parkinson disease dementia. At autopsy, all 3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were classified as low-probability AD based on NIA-Reagan criteria. The 2 PIB-positive individuals had abundant diffuse Abeta plaques but only sparse neuritic plaques and intermediate neurofibrillary tangle pathology. The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and low neurofibrillary tangle burden. 4
24. Johnson KA, Minoshima S, Bohnen NI, et al. 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. J Nucl Med. 2013;54(3):476-490. Review/Other-Dx N/A To assess a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. A set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. 4
25. Johnson KA, Minoshima S, Bohnen NI, et al. Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. J Nucl Med. 2013;54(7):1011-1013. Review/Other-Dx N/A To clarify and expand 3 topics discussed in the original appropriate use criteria for amyloid PET. The Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging defined dementia experts and their use of proper documentation to demonstrate the medical necessity of an amyloid PET scan; identified a specific subset of individuals with mild cognitive impairment for whom an amyloid PET scan is appropriate; and developed educational programs to increase awareness of the amyloid PET appropriate use criteria and provided instructions on how this test should be used in the clinical decision-making process. 4
26. Centers for Medicare & Medicaid Services. Coverage with Evidence Development. Amyloid PET.  Available at: https://www.cms.gov/Medicare/Coverage/Coverage-with-Evidence-Development/Amyloid-PET.html. Review/Other-Dx N/A To report on the CMS determination whether PET Aß imaging is covered under §1862(a)(1)(A) of the Social Security Act (“the Act”). CMS decision:A. The Centers for Medicare & Medicaid Services (CMS) has determined that the evidence is insufficient to conclude that the use of positron emission tomography (PET) amyloid-beta (Aß) imaging is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member for Medicare beneficiaries with dementia or neurodegenerative disease, and thus PET Aß imaging is not covered under §1862(a)(1)(A) of the Social Security Act (“the Act”).B. However, there is sufficient evidence that the use of PET Aß imaging is promising in two scenarios: (1) to exclude Alzheimer’s disease (AD) in narrowly defined and clinically difficult differential diagnoses, such as AD versus frontotemporal dementia (FTD); and (2) to enrich clinical trials seeking better treatments or prevention strategies for AD, by allowing for selection of patients on the basis of biological as well as clinical and epidemiological factors.Therefore, we will cover one PET Aß scan per patient through coverage with evidence development (CED), under §1862(a)(1)(E) of the Act, in clinical studies that meet the criteria in each of the paragraphs below. 4
27. McEvoy LK, Holland D, Hagler DJ, Jr., Fennema-Notestine C, Brewer JB, Dale AM. Mild cognitive impairment: baseline and longitudinal structural MR imaging measures improve predictive prognosis. Radiology. 2011;259(3):834-843. Observational-Dx 164 AD cases from 203 healthy controls To assess whether single-time-point and longitudinal volumetric MRI measures provide predictive prognostic information in patients with amnestic MCI. Individualized risk estimates from baseline MR examinations indicated that the 1-year risk of conversion to AD ranged from 3% to 40% (average group risk, 17%; odds ratio, 7.2 for highest vs lowest score quartiles). Including measures of 1-year change in global and regional volumes significantly improved risk estimates (P=001), with the risk of conversion to AD in the subsequent year ranging from 3% to 69% (average group risk, 27%; odds ratio, 12.0 for highest vs lowest score quartiles). 3
28. Desikan RS, Cabral HJ, Hess CP, et al. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease. Brain. 2009;132(Pt 8):2048-2057. Observational-Dx 313 individuals To determine whether automated MRI-based measures could identify MCI individuals with a high degree of accuracy. Baseline volumetric T1-weighted MRI of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with MCI, while the second cohort included 94 older controls and 57 MCI individuals. 65 patients with probable AD were also included for comparison. For the discrimination of MCI, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of AD, these three measures demonstrated an area under the curve of 1.0. 3
29. Karow DS, McEvoy LK, Fennema-Notestine C, et al. Relative capability of MR imaging and FDG PET to depict changes associated with prodromal and early Alzheimer disease. Radiology. 2010;256(3):932-942. Observational-Dx 80 controls, 68 patients with AD, 156 patients with amnestic MCI, 69 patients with single-domain amnestic MCI To quantify the effect sizes of regional metabolic and morphometric measures in patients with preclinical and mild AD to aid in the identification of noninvasive biomarkers for the early detection of AD. For all disease groups, the hippocampus showed the largest morphometric effect size and the entorhinal cortex showed the largest metabolic effect size. In mild AD, the Cohen d effect size for hippocampal volume (1.92) was significantly larger (P<.05) than that for entorhinal metabolism (1.43). Regression of regional atrophy substantially reduced most metabolic effects. For all group comparisons, the areas under the receiver operating characteristic curves were significantly larger for hippocampal volume than for entorhinal metabolism. 3
30. Chiang GC, Insel PS, Tosun D, et al. Identifying cognitively healthy elderly individuals with subsequent memory decline by using automated MR temporoparietal volumes. Radiology. 2011;259(3):844-851. Observational-Dx 149 patients To determine whether automated temporoparietal brain volumes can be used to accurately predict future memory decline among a multicenter cohort of cognitively healthy elderly individuals. Use of the most accurate region model, which included the hippocampus; parahippocampal gyrus; amygdala; superior, middle, and inferior temporal gyri; superior parietal lobe; and posterior cingulate gyrus, resulted in a fitted accuracy of 94% and a cross-validated accuracy of 81%. 3
31. Dickerson BC, Stoub TR, Shah RC, et al. Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurology. 2011;76(16):1395-1402. Observational-Dx Sample 1: 8 cognitively normal-AD converters, 25 cognitively normal-stable: Sample 2: 7 cognitively normal-AD converters, 25 cognitively normal-stable To test if the "disease signature" of AD-related cortical thinning, previously identified in patients with mild AD dementia, would be useful as a biomarker to detect anatomic abnormalities consistent with AD in cognitively normal adults who develop AD dementia after longitudinal follow-up. AD-signature cortical thinning in cognitively normal-AD converters in both samples was remarkably similar, about 0.2 mm (P<0.05). Despite this small absolute difference, Cohen d effect sizes for these differences were very large (>1). Of the 11 cognitively normal individuals with baseline low AD-signature thickness (=1 standard deviation below cohort mean), 55% developed AD dementia over nearly the next decade, while none of the 9 high AD-signature thickness individuals (=1 standard deviation above mean) developed dementia. This marker predicted time to diagnosis of dementia (hazard ratio = 3.4, P<0.0005); 1 standard deviation of thinning increased dementia risk by 3.4. 3
32. Tondelli M, Wilcock GK, Nichelli P, De Jager CA, Jenkinson M, Zamboni G. Structural MRI changes detectable up to ten years before clinical Alzheimer's disease. Neurobiol Aging. 2012;33(4):825 e825-836. Observational-Dx 148 subjects To investigate structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10 year follow-up using voxel-based morphometry and shape analyses of MRI data. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years. For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology. 3
33. Wang PN, Liu HC, Lirng JF, Lin KN, Wu ZA. Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment. Psychiatry Res. 2009;171(3):221-231. Observational-Dx 78: 58 with MCI; 20 normal To demonstrate decline rates in cognition and hippocampal volume in MCI subjects with stable clinical presentation and to investigate the effect of apolipoprotein E on the change rates of medial temporal structures and cognition in MCI. 19 (32.7%) MCI subjects converted to AD during an average 22.5-month follow-up period. The annual hippocampal atrophy rate was correlated with a decline in memory test scores. Compared to subjects with stable MCI and normal aging, progressive MCI had the highest annual decline rates in cognition and hippocampal volume. Logistic regression analysis showed that higher annual decline rates in hippocampal volume and global cognitive test scores were associated with conversion to AD. Although stable MCI subjects had little cognitive decline, their hippocampal atrophy rates were higher than those of normal aging controls. Therefore, accelerated hippocampal atrophy rates may be an early and important presentation in MCI subjects. 3
34. Korf ES, Wahlund LO, Visser PJ, Scheltens P. Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment. Neurology. 2004;63(1):94-100. Observational-Dx 75 patients To test the predictive accuracy of visually assessed MTA in MCI patients using a standardized visual rating scale. MTA assessed using a standardized visual rating scale was significantly associated with dementia at follow-up, with a hazard ratio of 1.5 for every point increase in atrophy score (P<0.001) and of 3.1 for the presence of atrophy based on the dichotomized atrophy score (P= 0.003).Visual assessment of MTA on brain MRI is a powerful and independent predictor of conversion to dementia in relatively young MCI patients. 2
35. Cavallin L, Axelsson R, Wahlund LO, et al. Voxel-based correlation between coregistered single-photon emission computed tomography and dynamic susceptibility contrast magnetic resonance imaging in subjects with suspected Alzheimer disease. Acta Radiol. 2008;49(10):1154-1161. Observational-Dx 24 total patients: 8 with AD; 10 with MCI; 6 controls To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), MCI, and AD. Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. Region-of-interest analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and 5 regions in DSC-MR. SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with AD. 3
36. Herholz K, Schopphoff H, Schmidt M, et al. Direct comparison of spatially normalized PET and SPECT scans in Alzheimer's disease. J Nucl Med. 2002;43(1):21-26. Observational-Dx 32 total: 26 with PAD; 6 healthy To detect and compare abnormal brain areas objectively and quantitatively using statistical parametric mapping. The overall correlation between PET and SPECT across the entire brain was significant but not close (average r = 0.43). The correlation between dementia severity and the number of abnormal voxels was closer for PET than for SPECT. Separation of patients from healthy volunteers by counting the number of abnormal voxels was possible over a much wider range of z thresholds with PET than with SPECT. The distinction between healthy volunteers and patients is less sensitive to threshold selection with PET than with SPECT and findings in the frontal, temporobasal, and temporomesial cortices and in the cerebellum may differ between the 2 techniques. 3
37. Weaver JD, Espinoza R, Weintraub NT. The utility of PET brain imaging in the initial evaluation of dementia. J Am Med Dir Assoc. 2007;8(3):150-157. Review/Other-Dx N/A To review PET brain imaging in the initial assessment and diagnosis of dementia, including its place in current guidelines and role in diagnostic algorithms, its applicability in differentiating among various dementia syndromes and major psychiatric disorders, and some of the controversies surrounding its utility in general clinical practice. No results stated in abstract. 4
38. Fayed N, Davila J, Oliveros A, Castillo J, Medrano JJ. Utility of different MR modalities in mild cognitive impairment and its use as a predictor of conversion to probable dementia. Acad Radiol. 2008;15(9):1089-1098. Observational-Dx 119 consecutive amnesic MCI patients To determine whether findings from a combined use of hydrogen-1 MRS, PWI, and DWI would predict conversion from amnesic MCI to dementia and to compare the diagnostic accuracy in discriminating patients with PAD, mixed dementia, DLB, pre-AD MCI, vascular MCI, and anxious or depression patients with cognitive impairment. N-acetylaspartate/creatine ratios in posterior cingulated gyri predict the conversion to PAD with a sensitivity of 82% and specificity of 72%, and N-acetylaspartate/creatine ratios in the left occipital cortex had a sensitivity of 78% and specificity of 69%. Significant differences in N-acetylaspartate/creatine, N-acetylaspartate/myoinositol, N-acetylaspartate/choline, myoinositol/N-acetylaspartate, and choline/creatine ratios. N-acetylaspartate/creatine ratios in posterior cingulated gyri and left occipital cortex can predict the conversion from MCI to dementia with high sensitivity and specificity. MRS can differentiate AD from MCI, but cannot differentiate the types of MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows differentiating it from MCI. 3
39. Soher BJ, Doraiswamy PM, Charles HC. A review of 1H MR spectroscopy findings in Alzheimer's disease. Neuroimaging Clin N Am. 2005;15(4):847-852, xi. Review/Other-Dx N/A To review clinical, proton MRS methods in the diagnosis of AD. MRS is a robust tool for measuring metabolic changes in vivo noninvasively in patients who have AD. Two metabolic changes in particular typically are measured in AD, decreased N-acetylaspartate and increased myoinositol. The use of the N-acetylaspartate/myoinositol ratio shows great promise for delineating AD from controls. 4
40. Kantarci K, Jack CR, Jr. Neuroimaging in Alzheimer disease: an evidence-based review. Neuroimaging Clin N Am. 2003;13(2):197-209. Review/Other-Dx N/A An evidence-based review focuses on application of neuroimaging to the clinical diagnosis of AD and the use of neuroimaging as a surrogate marker for disease onset and progression in AD. No results stated in abstract. 4
41. Walhovd KB, Fjell AM, Brewer J, et al. Combining MR imaging, positron-emission tomography, and CSF biomarkers in the diagnosis and prognosis of Alzheimer disease. AJNR Am J Neuroradiol. 2010;31(2):347-354. Observational-Dx 42 controls, 73 with MCI, and 38 with AD; 2-year clinical follow-up data for 36 controls, 51 with MCI, and 25 with AD To combine MRI, FDG-PET, and CSF biomarkers in the diagnostic classification and 2-year prognosis of MCI and AD, by examining the following: 1) which measures are most sensitive to diagnostic status, 2) to what extent the methods provide unique information in diagnostic classification, and 3) which measures are most predictive of clinical decline. Hippocampal volume, retrosplenial thickness, and t-tau/Abeta42 uniquely predicted diagnostic group. Change in CDR-SB was best predicted by retrosplenial thickness; MMSE, by retrosplenial metabolism and thickness; and delayed logical memory, by hippocampal volume. 3
42. Matthews B, Siemers ER, Mozley PD. Imaging-based measures of disease progression in clinical trials of disease-modifying drugs for Alzheimer disease. Am J Geriatr Psychiatry. 2003;11(2):146-159. Review/Other-Dx N/A Review and assess imaging-based strategies for measuring the rate of progression of AD. Many of imaging-based strategies show promise as measures of disease progression. 4
43. Mueller SG, Weiner MW, Thal LJ, et al. The Alzheimer's disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15(4):869-877, xi-xii. Review/Other-Dx N/A To review benefits and implementation of the Alzheimer's Disease Neuroimaging Initiative as a result of the growth of increasing age, the incidence, and socioeconomic impact of AD. There is increasing evidence that neuroimaging and CSF and blood biomarkers may provide information that may reduce sample sizes and observation periods. The AD Neuroimaging Initiative will help identify clinical, neuroimaging, and biomarker outcome measures that provide the highest power for measurement of longitudinal changes and for prediction of transitions. 4
44. Goto H, Ishii K, Uemura T, et al. Differential diagnosis of dementia with Lewy Bodies and Alzheimer Disease using combined MR imaging and brain perfusion single-photon emission tomography. AJNR Am J Neuroradiol. 2010;31(4):720-725. Observational-Dx 19 patients with mild DLB; 19 age- and cognitive decline-matched patients with mild AD To evaluate the usefulness of combining MRI and SPECT to discriminate mild DLB from AD. The striatal volume ratio in the DLB group was significantly lower than that in the AD group. The occipital SPECT ratio in the DLB group was lower than that in the AD group. The mean area under the receiver operator characteristic curve from combined MRI and SPECT (area under the curve = 0.898) was higher than that from MRI (area under the curve = 0.679) or SPECT (area under the curve = 0.798) alone. 3
45. Shimizu S, Hanyu H, Hirao K, Sato T, Iwamoto T, Koizumi K. Value of analyzing deep gray matter and occipital lobe perfusion to differentiate dementia with Lewy bodies from Alzheimer's disease. Ann Nucl Med. 2008;22(10):911-916. Observational-Dx 79 patients: 30 with probable DLB; 49 with PAD To explore characteristics of regional cerebral blood flow pattern changes to improve the identification of DLB, in addition to occipital hypoperfusion. The DLB group showed a significant relative regional cerebral blood flow increase in the bilateral striatum and thalamus, and a significant relative regional cerebral blood flow decrease in the bilateral occipital lobe when compared with the AD group. Determining the hyperperfusion in the thalamus together with the hypoperfusion in the occipital lobe enabled a more accurate differentiation between DLB and AD than studying individual areas. Studying the relative increase of regional cerebral blood flow in the deep gray matter, and the relative decrease of that in the occipital lobe achieved a high differentiation between DLB and AD. This suggests that determining both an increase and a decrease in regional cerebral blood flow pattern may be important in differentiating between the two diseases. 3
46. Walker Z, Jaros E, Walker RW, et al. Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry. 2007;78(11):1176-1181. Observational-Dx 20: 8 with DLB; 9 with AD; 3 with other diagnoses To determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. Initial DLB diagnosis: Sensitivity 75%, Specificity 42%, FP-CIT scan for diagnosis of DLB: Sensitivity 88%, Specificity 100%, FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone. 2
47. Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. AJNR Am J Neuroradiol. 2005;26(10):2481-2487. Observational-Dx 112 patients from 64 families To study MRI abnormalities in a prospectively recruited cohort of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy patients. There is a characteristic pattern of MRI abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy that aids in differential diagnosis. 3
48. Collie DA, Summers DM, Sellar RJ, et al. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. AJNR Am J Neuroradiol. 2003;24(8):1560-1569. Observational-Dx 82 suspected cases of vCJD To evaluate pulvinar sign prospectively and further define the MRI characteristics of vCJD. (Symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalamus (pulvinar sign) on brain MRI.) Pulvinar sign was present on 7 (9%) of 75 T1-weighted, 77 (71%) of 108 T2-weighted, 47 (81%) of 58 proton density-weighted, and 30 (100%) of 30 FLAIR images. DWI were available in two cases and were positive for the pulvinar sign in one. Other features were hyperintensity of the dorsomedial thalamic nuclei (93%), caudate head (40%), and periaqueductal gray matter (83%) on FLAIR images. In the appropriate clinical context, demonstration of the pulvinar sign on MRI is a highly accurate diagnostic sign for vCJD. FLAIR sequence is more sensitive than other sequences. Positive MR images may obviate more invasive diagnostic tests in most cases. 3
49. Kallenberg K, Schulz-Schaeffer WJ, Jastrow U, et al. Creutzfeldt-Jakob disease: comparative analysis of MR imaging sequences. AJNR Am J Neuroradiol. 2006;27(7):1459-1462. Observational-Dx 157; 65 classified with CJD To compare the value of different MRI in the diagnosis of CJD. Cortical abnormalities were present in 70 patients (45%) and were visible in 80% (35/44) of all available DWI examinations. The basal ganglia were affected in 94 patients (60%), in particular in the caudate nucleus; the most sensitive sequences were DWI (64%) and PD-weighted (63%). A thalamic involvement was more frequently diagnosed on PD-weighted images (19%) and DWI (14%) than on FLAIR or T2-weighted images. PD-weighted images and DWI show better results in the diagnosis of signal intensity changes in the basal ganglia compared with T2-weighted DWI is the most sensitive MRI technique in the diagnosis of CJD. 3
50. Tschampa HJ, Kallenberg K, Urbach H, et al. MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: a study on inter-observer agreement. Brain. 2005;128(Pt 9):2026-2033. Observational-Dx 193 suspected sCJD patients To investigate the reliability of MRI in the sCJD diagnosis. Sensitivity of MRI in clinically probable or autopsy-proven sCJD was 59.7% for Observer 1, 58.3% for Observer 2 and 70.8% for Observer 3. Specificity was high (84.2%, 89.5% and 81.6%, respectively). DWI sequences best showed the pathologic changes, followed by FLAIR. Periodic sharp and slow wave complexes were detected in the EEG in 32% (sensitivity); the 14-3-3 proteins in CSF were elevated in 91%. Detection of hyperintense basal ganglia in MRI helps to improve the clinical diagnosis. 2
51. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(3 Suppl):S4-16; discussion ii-v. Review/Other-Dx N/A To facilitate future epidemiological studies of idiopathic NPH, promote more accurate diagnosis, and improve treatment outcome. Evidence-based guidelines for the clinical diagnosis of idiopathic NPH are proposed. 4
52. Dickerson BC, Bakkour A, Salat DH, et al. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009;19(3):497-510. Observational-Dx N/A To define regions of interest and determine whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This “disease signature” approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases. 3
53. Paulsen JS, Zimbelman JL, Hinton SC, et al. fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's Disease. AJNR Am J Neuroradiol. 2004;25(10):1715-1721. Experimental-Dx 21 patients To examine the sensitivity of fMRI in detecting early neurodegenerative changes related to HD compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes. Functional neuroimaging measures may prove useful for tracking the evolution of changes in neural function during the earliest stages of pre-HD. 2
54. Hayflick SJ, Hartman M, Coryell J, Gitschier J, Rowley H. Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. AJNR Am J Neuroradiol. 2006;27(6):1230-1233. Review/Other-Dx 49; 29 with PANK2 mutations To investigate correlations between brain MRI changes, mutation status, and clinical disease features of patients with a clinical diagnosis of neurodegeneration with brain iron accumulation. MRI signal intensity abnormalities in the globus pallidus can distinguish patients with mutations in PANK2 from those lacking a mutation, even in the early stages of disease. 4
55. Hayflick SJ, Westaway SK, Levinson B, et al. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003;348(1):33-40. Review/Other-Dx 123 patients with a diagnosis of Hallervorden-Spatz syndrome To compare the clinical and radiographic features of patients with Hallervorden-Spatz syndrome with and without mutations in PANK2. MRI abnormalities outside the globus pallidus, including cerebral or cerebellar atrophy, were more common and more severe in mutation-negative patients. No specific MRI changes could be distinguished among the mutation-negative patients.PANK2 mutations are associated with all cases of classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. 4
56. Kruer MC, Boddaert N, Schneider SA, et al. Neuroimaging features of neurodegeneration with brain iron accumulation. AJNR Am J Neuroradiol. 2012;33(3):407-414. Review/Other-Dx N/A To outline the known subtypes of neurodegeneration with brain iron accumulation, delineate their clinical and radiographic features and suggest an algorithm for evaluation. Neurodegeneration with brain iron accumulation characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of neurodegeneration with brain iron accumulation is made on the basis of the combination of representative clinical features along with MRI evidence of iron accumulation. 4
57. Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ. Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):968-975. Review/Other-Dx N/A To define key issues in the diagnosis of PD, to define features influencing progression, and to make evidence-based recommendations. Early falls, poor response to levodopa, symmetry of motor manifestations, lack of tremor, and early autonomic dysfunction are probably useful in distinguishing other parkinsonian syndromes from PD. Levodopa or apomorphine challenge and olfactory testing are probably useful in distinguishing PD from other parkinsonian syndromes. Predictive factors for more rapid motor progression, nursing home placement, and shorter survival time include older age at onset of PD, associated comorbidities, presentation with rigidity and bradykinesia, and decreased dopamine responsiveness. Future research into methods for earlier and more accurate diagnosis of the disease and identification and clarification of predictive factors of rapid disease progression is warranted. 4
58. Seppi K, Poewe W. Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am. 2010;20(1):29-55. Review/Other-Dx N/A Discussion of static or structural conventional MRI techniques including standard T2-weighted, T1-weighted, and proton-density sequences, as well as different advanced techniques, including methods to assess regional cerebral atrophy quantitatively such as magnetic resonance volumetry, DTI and DWI, and magnetization transfer imaging, to assist in the differential diagnosis of neurodegenerative parkinsonian disorders. No results stated in abstract. 4
59. Tatsch K. Extrapyramidal syndromes: PET and SPECT. Neuroimaging Clin N Am. 2010;20(1):57-68. Review/Other-Dx N/A An overview of the current PET and SPECT applications for diagnosing Extrapyramidal syndromes and focuses on their use in clinical practice. No results stated in abstract. 4
60. Karimi M, Tian L, Brown CA, et al. Validation of nigrostriatal positron emission tomography measures: critical limits. Ann Neurol. 2013;73(3):390-396. Observational-Dx 16 monkeys To compare striatal uptake for PET tracers with in vitro measures of nigral cell counts and striatal dopamine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. Striatal uptake for each radiotracer (FD, DTBZ, CFT) correlated with stereologic nigral cell counts only for nigral loss <50% (r2=0.84, r2=0.86, r2=0.87, P<0.001 respectively; n=10). In contrast, striatal uptake correlated with striatal dopamine over the full range of dopamine depletion (r2=0.95, r2=0.94, r2=0.94, P<0.001; n=16). Interestingly, indices of striatal uptake of FD, DTBZ, and CFT correlated strongly with each other (r2=0.98, P<0.001). 3
61. Grosset D, Grachev I, O’Brien J, et al. Integrated Analysis of 123IFP-CIT (DaTscan; Ioflupane I123 Injection) SPECT Brain Imaging - Diagnostic Effectiveness in Patients with Movement Disorders and/or Dementia (S8.004). Neurology. 2014;82(10 Supplement):S8.004. Review/Other-Dx 4 studies To conduct a pooled analysis of 4 clinical trials to better estimate the diagnostic performance of 123IFP-CIT. Pooling the 4 studies, 928 subjects were enrolled, 849 were dosed, and 764 completed their respective study. Across all studies when images were assessed by on-site readers, 123IFP-CIT diagnostic effectiveness had an overall (95% confidence interval) sensitivity of 91.9% (88.7, 94.5) and specificity of 83.6% (78.7, 87.9). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8, 90.4) and specificity was 91.2% (89.0, 93.0). For subjects with Parkinsonian Syndromes vs Essential Tremor and DLB vs AD, the sensitivity and specificity was similar. 4
62. Tolosa E, Borght TV, Moreno E. Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study. Mov Disord. 2007;22(16):2346-2351. Observational-Dx 85 patients To establish the diagnostic accuracy of DaTSCAN imaging by comparing the result obtained with the technique during the original clinically uncertain parkinsonian syndromes study with a clinical diagnosis obtained after 2-years follow-up, and to ascertain whether a second scan could eliminate any residual diagnostic uncertainty among those with an inconclusive diagnosis. 85/118 patients (72%) were available at follow-up. In 8/85 patients the neurologist was unable to provide a definite diagnosis (named as inconclusive). At follow-up, clinical diagnosis agreed with initial DaTSCAN SPECT results in 69/77 patients (90%) in whom a specific diagnosis was established. A second SPECT scan was performed if clinical diagnosis at follow-up differed to that suggested by the initial scan (n = 8) or was inconclusive (n = 8). Among 8 patients whose clinical diagnosis differed to DaTSCAN images, a second scan was performed in 6 (2 refused) and the results supported the final clinical diagnosis in 4. Follow-up DaTSCAN SPECT helped to establish a diagnosis in 7/8 patients (87.5%) with a previously inconclusive diagnosis. 3
63. Karimi M, Perlmutter JS. MRI measures predict progressive supranuclear palsy: clinically useful? Neurology. 2011;77(11):1028-1029. Review/Other-Dx N/A To present the MRPI to distinguish patients with PSP-P from a pool of patients with clinically unclassifiable parkinsonism. No results stated in abstract. 4
64. Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage. 2005;26(3):912-921. Observational-Dx 135 PD patients To assess the utility of FDG-PET in the differential diagnosis of individual patients with clinical parkinsonism. Blinded computer assessment agreed with clinical diagnosis in 92.4% of all subjects. Concordance of visual inspection with clinical diagnosis was achieved in 85.4% of the patients scanned. This study demonstrates that FDG-PET performed at the time of initial referral for Parkinsonism accurately predicted the clinical diagnosis of individual patients made at subsequent follow-up. Computer-assisted methodologies may be particularly helpful in situations where experienced readers of FDG-PET images are not readily available. 2
65. Powers WJ, Videen TO, Markham J, Black KJ, Golchin N, Perlmutter JS. Cerebral mitochondrial metabolism in early Parkinson's disease. J Cereb Blood Flow Metab. 2008;28(10):1754-1760. Observational-Dx 12 patients To assess the role of defects in mitochondrial metabolism in the pathogenesis of PD by measuring CMRO2 and CMRglc in vivo with PET in early, never-medicated participants with PD and compared to age-matched normal controls. The primary analysis showed a statistically significant 24% increase in bihemispheric CMRO2 and no change in CMRO2/CMRglc. These findings are inconsistent with a defect in mitochondrial oxidative phosphorylation due to reduced activity of the mitochondrial ETS. Since PD symptoms were already manifest, deficient energy production due to a reduced activity of the mitochondrial ETS cannot be a primary mechanism of neuronal death in early PD. Alternatively, this general increase in CMRO2 could be due, not to increased metabolic demand, but to an uncoupling of ATP production from oxidation in the terminal stage of oxidative phosphorylation. 3
66. Glodzik-Sobanska L, Rusinek H, Mosconi L, et al. The role of quantitative structural imaging in the early diagnosis of Alzheimer's disease. Neuroimaging Clin N Am. 2005;15(4):803-826, x. Review/Other-Dx N/A To review the role of structural neuroimaging in the diagnosis of AD. No results stated in abstract. 4
67. Righini A, Antonini A, De Notaris R, et al. MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol. 2004;25(6):927-932. Observational-Dx 25 patients with PSP and 27 with PD To determine whether an abnormal superior midbrain profile (flat or concave aspect) is a more practical diagnostic parameter for PSP. The finding of an abnormal superior profile of the midbrain had 68% sensitivity and 88.8% specificity. Midbrain atrophy had 68% sensitivity and 77.7% specificity. Tegmental T2 hyperintensity had 100% specificity but poor sensitivity (28%). Only 14.8% of patients with PD and 24% of those with PSP had abnormal putaminal T2 hypointensity; none had proton-density hyperintensity. With PSP, the average midbrain diameter was smaller than that with PD, but an important overlap was observed. Reader discordance was lower for the midbrain superior profile sign (eight of 52 cases); this was similar for tegmental hyperintensity (nine of 52 cases) and higher for midbrain atrophy (16 of 52 cases). 3
68. Morelli M, Arabia G, Novellino F, et al. MRI measurements predict PSP in unclassifiable parkinsonisms: a cohort study. Neurology. 2011;77(11):1042-1047. Observational-Dx 45 patients To investigate the usefulness of MRPI in predicting the clinical evolution in PSP of patients with clinically unclassifiable parkinsonism, i.e., parkinsonism not fulfilling the established clinical diagnostic criteria for any parkinsonism disorders, using a cohort study. Duration of clinical follow-up in these 2 groups was 28.4 +/- 11.7 months (mean +/- SD). None of the patients with clinically unclassifiable parkinsonism with normal MRPI values fulfilled established clinical criteria for PSP (follow-up ranging from 24 to 60 months). By contrast, 1/15 patients with clinically unclassifiable parkinsonism with abnormal MRPI values (higher than 13.55) developed during the follow-up (range from 6 to 48 months) additional clinical features characteristic of probable (1 patient) or possible (10 patients) PSP. MRPI showed a higher accuracy in predicting PSP (92.9%) than clinical features, such as vertical ocular slowness or first-year falls (61.9% and 73.8%, respectively). 2
69. Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25(34):7709-7717. Review/Other-Dx 764 patients To explore AD and antecedent factors associated with AD using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related fMRI studies further revealed that these cortical regions are active during successful memory retrieval in young adults. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment. 4