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Appropriateness Criteria

Reference Study Type Patients/Events Study Objective(Purpose of Study) Study Results 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. Skrobot OA, O'Brien J, Black S, et al. The Vascular Impairment of Cognition Classification Consensus Study. Alzheimer's & Dementia. 13(6):624-633, 2017 Jun. Review/Other-Dx 122 patients To tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) Vascular Impairment of Cognition Classification Consensus Study (VICCCS) had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined vascular cognitive impairment (VCI) including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. 4
3. 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
4. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's dement.. 7(3):263-9, 2011 May. Review/Other-Dx N/A To present criteria for all-cause dementia and for AD dementia. N/A 4
5. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's dement.. 7(3):270-9, 2011 May. Review/Other-Dx N/A To develop criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. N/A 4
6. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's dement.. 7(3):280-92, 2011 May. Review/Other-Dx N/A To further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. No results stated in abstract. 4
7. Hampel H, Burger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K. Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. [Review] [96 refs]. Alzheimer's dement.. 4(1):38-48, 2008 Jan. Review/Other-Dx N/A To perform a survey of recent research, focusing on core biomarker candidates in AD. A number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy, hold promise as biomarkers. These neurobiologic measures appear to relate closely to pathophysiologic, neuropathologic, and clinical data, such as hyperphosphorylation of tau, amyloid beta (Abeta) metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, functional and cognitive decline, as well as risk of future decline. Current advances in the neuroimaging of mediotemporal, neocortical, and subcortical areas of the brain of mild cognitive impairment (MCI) and AD subjects are presented. CSF levels of Abeta42, tau, and hyperphosphorylated tau protein (p-tau) can distinguish subjects with MCI who are likely to progress to AD. They also show preclinical alterations that predict later development of early AD symptoms. Studies on plasma Abeta are not entirely consistent, but recent findings suggest that decreased plasma Abeta42 relative to Abeta40 might increase the risk of AD. Increased production of Abeta in aging is suggested by elevation of BACE1 protein and enzyme activity in the brain and CSF of subjects with MCI. CSF tau and p-tau are increased in MCI as well and show predictive value. Other biomarkers might indicate components of a cascade initiated by Abeta, such as oxidative stress or inflammation. These merit further study in MCI and earlier. 4
8. Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet neurol.. 13(6):614-29, 2014 Jun. Review/Other-Dx N/A To review the strengths and limitations of the International Working Group (IWG) research diagnostic criteria and proposes advances to improve the diagnostic framework. No results stated in the abstract 4
9. 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
10. 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
11. 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
12. 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
13. George AE, de Leon MJ, Stylopoulos LA, et al. CT diagnostic features of Alzheimer disease: importance of the choroidal/hippocampal fissure complex. AJNR Am J Neuroradiol. 11(1):101-7, 1990 Jan-Feb. Review/Other-Dx 34 patients To study the usefulness of detecting temporal-lobe structural changes on CT in making the diagnosis of Alzheimer disease. All the temporal-lobe evaluations of the five variables measured were significantly associated with the presence or absence of Alzheimer disease. Almost all Alzheimer patients showed evidence of mild or greater severity of overall temporal-lobe atrophy. The absence of temporal-lobe atrophy, seen in approximately one half the normal cases, identified normal individuals with a high degree of specificity (95%). The presence of characteristic hippocampal lucency, apparently due to enlargement of the choroid and hippocampal fissures, showed the highest sensitivity and classification accuracy of all the variables tested (82 and 80% respectively; p less than .001), correctly identifying 82% of Alzheimer patients and 80% of Alzheimer patients and control subjects. 4
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
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. Morris E, Chalkidou A, Hammers A, Peacock J, Summers J, Keevil S. Diagnostic accuracy of (18)F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. [Review]. Eur J Nucl Med Mol Imaging. 43(2):374-85, 2016 Feb. Meta-analysis 9 studies; 662 patients To perform a systematic review and metastasis of the literature published between 1990 and 2014 for studies exploring the diagnostic accuracy of florbetaben, florbetapir and flutemetamol in AD. The meta-analysis results showed that pooled sensitivity and specificity values were in general high for all tracers. This was confirmed by calculating likelihood ratios. A patient with a positive ratio is much more likely to have AD than a patient with a negative ratio, and vice versa. However, specificity was higher when only patients with AD were compared with healthy controls. This systematic review and meta-analysis found no marked differences in the diagnostic accuracy of the three beta-amyloid radiotracers. All tracers perform better when used to discriminate between patients with AD and healthy controls. Good
22. 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
23. 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
24. 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
25. 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
26. Frey KA, Lodge MA, Meltzer CC, et al. ACR-ASNR Practice Parameter for Brain PET/CT Imaging Dementia. Clin Nucl Med. 41(2):118-25, 2016 Feb. Review/Other-Dx N/A To present a practice parameter that is for both FDG and amyloid brain PET or PET/computed tomography (CT) for patients with cognitive decline, and has been developed collaboratively by the American College of Radiology (ACR) and the American Society for Neuroradiology (ASNR). No results stated in abstract. 4
27. 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
28. 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
29. Targosz-Gajniak MG, Siuda JS, Wicher MM, et al. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci. 335(1-2):58-63, 2013 Dec 15. Experimental-Dx 41 patients To investigate if there is a difference in brain metabolism between stable MCI patients and converters to dementia and if a use of (1)H-MRS can predict the conversion from MCI to dementia. Twelve subjects with MCI progressed to Alzheimer's disease (AD) after one year. Analysis showed that the NAA/Cr ratio in the LH was significantly lower in MCI patients than in controls (p=0.008), but there were no differences in metabolite ratios at baseline between MCI converters and stable subjects. mI/Cr ratio in RPL predicted the conversion to AD with sensitivity 70% and specificity 85% (p<0.0004). Coexistence of diabetes improved prediction, yielding 70% sensitivity and 96% specificity (p<0.0001). 2
30. 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
31. Sperling R.. Potential of functional MRI as a biomarker in early Alzheimer's disease. [Review]. Neurobiol Aging. 32 Suppl 1:S37-43, 2011 Dec. Review/Other-Dx N/A To further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. No results stated in abstract. 4
32. Hafkemeijer A, van der Grond J, Rombouts SA. Imaging the default mode network in aging and dementia. [Review]. Biochim Biophys Acta. 1822(3):431-41, 2012 Mar. Review/Other-Dx N/A To review whether normal aging and dementia affect task-induced deactivation and functional connectivity in the DMN (default mode network). The majority of studies show a decreased DMN functional connectivity and task-induced DMN deactivations along a continuum from normal aging to mild cognitive impairment and to Alzheimer's disease (AD). Even subjects at risk for developing AD, either in terms of having amyloid plaques or carrying the APOE4 allele, showed disruptions in the DMN. 4
33. Frisoni GB, Fox NC, Jack CR Jr, Scheltens P, Thompson PM. The clinical use of structural MRI in Alzheimer disease. [Review] [143 refs]. Nat Rev Neurol. 6(2):67-77, 2010 Feb. Review/Other-Dx N/A To discuss our review of structural imaging based on magnetic resonance as an integral part of the clinical assessment of patients with suspected Alzheimer dementia. No results stated in abstract. 4
34. 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
35. O'Donovan J, Watson R, Colloby SJ, Blamire AM, O'Brien JT. Assessment of regional MR diffusion changes in dementia with Lewy bodies and Alzheimer's disease. Int Psychogeriatr. 26(4):627-35, 2014 Apr. Experimental-Dx 71 patients To examine diagnosis complexities involving Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), as common forms of dementia. Compared to controls, DLB subjects were characterized by reduced FA (p = 0.016) and increased MD (p = 0.007) in the precuneus. Amygdala diffusivity was positively correlated with UPDRS-III score in DLB (p = 0.003). In AD, reduced FA in the precuneus was also observed compared to controls (p = 0.026), and was associated with impaired global cognition (MMSE score) (p = 0.03). 1
36. Zhang B, Zhang JG, Zhao H, et al. Evaluation of apparent diffusion coefficient mappings in amnestic mild cognitive impairment using an image analysis software brain search. Acta Radiol. 52(10):1147-54, 2011 Dec 01. Experimental-Dx 51 patients To investigate the ADC value for aMCI and AD using Brain Search (BS) software based on anatomical volumes of interest (AVOI). During the pathological process of AD, the changes of water diffusivity appeared first in the left hippocampus, then gradually progressed to the bilateral sides and eventually displayed right lateralization. The ADC values from aMCI were obviously elevated compared to the values from the NC group in the left limbic cortex. Between the AD and NC groups, the significantly different brain areas included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and the Temporal and Frontal lobes. There was a negative correlation between the ADC values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ. Additionally, the ADC values were positively correlated with the scores from CDR, ADL, and ADAS-Cog. 3
37. 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
38. 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
39. 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
40. 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
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. Trzepacz PT, Yu P, Sun J, et al. Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia. Neurobiol Aging. 35(1):143-51, 2014 Jan. Observational-Dx 50 subjects To compare Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimer’s dementia using datafrom the Alzheimer’s Disease Neuroimaging Initiative cohort Multivariate modeling found that among individual modalities, MRI had the highest predictive accuracy (67%) which increased by 9% to 76% when combined with PIB-PET, producing the highest accuracy among any biomarker combination. Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET. 3
43. Warren JD, Rohrer JD, Rossor MN. Clinical review. Frontotemporal dementia. [Review]. BMJ. 347:f4827, 2013 Aug 06. Review/Other-Dx N/A To provide a general overview of Frontotemporal dementia (FTD), emphasising clinical aspects and highlighting recent progress and prospects. No results stated in abstract 4
44. Diehl-Schmid J, Onur OA, Kuhn J, Gruppe T, Drzezga A. Imaging frontotemporal lobar degeneration. [Review]. Curr Neurol Neurosci Rep. 14(10):489, 2014 Oct. Review/Other-Dx N/A To provide a synopsis on the value of magnetic resonance imaging-based and molecular imaging procedures in frontotemporal lobar degeneration (FTLD). No results stated in abstract 4
45. Centers for Medicare & Medicaid Services. National Coverage Analysis (NCA) for Positron Emission Tomography (FDG) and Other Neuroimaging Devices for Suspected Dementia (CAG-00088R). Review/Other-Dx N/A To review the National Coverage Analysis (NCA) for Positron Emission Tomography (FDG) and Other Neuroimaging Devices for Suspected Dementia No results stated in the abstract 4
46. Kantarci K.. 1H magnetic resonance spectroscopy in dementia. [Review] [72 refs][Erratum appears in Br J Radiol. 2013 Jun;86(1026):20139005]. Br J Radiol. 80 Spec No 2:S146-52, 2007 Dec. Review/Other-Dx N/A To review the potential clinical application of MRS in ageing and dementia. No results stated in abstract 4
47. Rombouts SA, van Swieten JC, Pijnenburg YA, Goekoop R, Barkhof F, Scheltens P. Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD. Neurology. 60(12):1904-8, 2003 Jun 24. Observational-Dx Seven patients with FTD and seven patients with AD To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. 2
48. Dopper EG, Rombouts SA, Jiskoot LC, et al. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology. 83(2):e19-26, 2014 Jul 08. Observational-Dx 75 patients To investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of MAPT (microtubule-associated protein tau) or GRN (progranulin) mutations. Carriers (n = 39) and noncarriers (n = 36) had similar neuropsychological performance, except for lower Letter Digit Substitution Test scores in carriers. Worse performance on Stroop III, Rivermead Behavioral Memory Test, and Happé Cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy in the right uncinate fasciculus was found in carriers compared with controls. Reductions in functional connectivity between anterior midcingulatecortex and frontoinsula and several other brain regions were found in carriers compared with controls and correlated with higher age in carriers, but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found, except for a small cluster of higher volume in the precentral gyrus in carriers. 2
49. Zhang Y, Tartaglia MC, Schuff N, et al. MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes. J Alzheimers Dis. 33(2):431-44, 2013. Observational-Dx Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects To investigate to what extent the pattern of white matter microstructural alterations in frontotemporal lobar degeneration (FTLD) subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Compared to controls, behavioral variant frontotemporal dementia (bvFTD), SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy. 3
50. Talbot PR, Lloyd JJ, Snowden JS, Neary D, Testa HJ. A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?. J Neurol Neurosurg Psychiatry. 64(3):306-13, 1998 Mar. Observational-Dx 363 patients To provide the clinician with a guide to the clinical utility of 99mTc- HMPAO single photon emission computed tomography (SPECT) and to theinterpretation of specific test results in the differential diagnosis of dementia. Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer’s disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer’s disease, vascular dementia, or Lewy body disease. “Patchy” CBF changes significantly increased the odds of a patient having vascular dementia asopposed to Alzheimer’s disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to thedifferentiation of any of these forms of dementia. 2
51. 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
52. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. [Review]. Neurology. 89(1):88-100, 2017 Jul 04. Review/Other-Dx N/A To present the revised Dementia with Lewy Bodies (DLB) criteria incorporating new developments since last consortium and result from a review process thatcombined the reports of 4 multidisciplinary, expert working groups with a meeting that included patient and care partner participation No results stated in abstract 4
53. Donaghy P, Thomas AJ, O'Brien JT. Amyloid PET Imaging in Lewy body disorders. [Review]. Am J Geriatr Psychiatry. 23(1):23-37, 2015 Jan. Review/Other-Dx 18 studies To review the amyloid imaging studies in Lewy body (LB) disorders. LB disorders are associated with lower mean cortical Ab ligand binding compared with Alzheimer disease. In DLB and PDD many subjects have normal levelsof cortical Ab, though a subset show increased Ab ligand binding. Those with DLB show greater ligand binding than PDD; binding does not appear to be increased in PD without dementia. Cortical Ab deposition may be a factor in the development of cognitive impairment in some cases of dementia in LB disorders. Amyloid imaging is of limited use in the diagnosis of LB disorders but Ab deposition may predict the future development of dementia in PD. Reports of correlation between Ab deposition and symptom profile, severity, and progression have been inconsistent. Some results suggest a synergistic interaction between Ab and a-synuclein. Interpretation of the current evidence is hampered by differing methodologies across studies and small sample sizes. Large, prospective longitudinal studies are needed to clarify the association of Ab with symptom development, progression, severity, and treatment response in LB disorders. 4
54. 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
55. Graff-Radford J, Boeve BF, Murray ME, et al. Regional proton magnetic resonance spectroscopy patterns in dementia with Lewy bodies. Neurobiol Aging. 35(6):1483-90, 2014 Jun. Observational-Dx Patients with DLB (n = 34) and AD dementia (n = 35) To determine the Magnetic resonance spectroscopy (MRS) changes in dementia with Lewy bodies (DLB) with low probability of overlapping Alzheimer’sdisease (AD) pathology. DLB patients were characterized by decreased N-acetylaspartate/creatine (NAA/Cr) in the occipital voxel. AD patients were characterized bylower NAA/Cr in the frontal and posterior cingulate voxels. Normal NAA/Cr levels in the frontal voxel differentiated DLB patients with preserved hippocampal volumes from AD patients. DLB and AD patients had elevated choline/creatine, and myo-Inositol/creatine in the posterior cingulate. MRS abnormalitiesassociated with loss of neuronal integrity localized to the occipital lobes in DLB, and the posterior cingulate gyri and frontal lobes in AD. 3
56. Kenny ER, Blamire AM, Firbank MJ, O'Brien JT. Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer's disease. Brain. 135(Pt 2):569-81, 2012 Feb. Observational-Dx 47 subjects: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer’s disease and 16 control subjects. To investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer’s disease and healthy controls Both subjects with dementia with Lewy bodies and Alzheimer’s disease showed greaterconnectivity than control subjects. Compared with controls, the dementia with Lewy bodies group had greater connectivitybetween the right posterior cingulate cortex and other brain areas. In dementia with Lewy bodies, there were no significantdifferences in hippocampal connectivity compared with controls, but in Alzheimer’s disease left hippocampal connectivity wasgreater compared with controls. There were no significant differences between groups for precuneus or primary visual cortexconnectivity. No seed regions showed significantly less connectivity in subjects with dementia with Lewy bodies or Alzheimer’sdisease compared with controls. We found greater connectivity with the posterior cingulate in dementia with Lewy bodies andwith the hippocampus in Alzheimer’s disease. Consistent with the known relative preservation of memory in dementia withLewy bodies compared with Alzheimer’s disease, hippocampal connectivity was not found to be greater in dementia with Lewybodies. Importantly, while metabolic imaging shows functional change in primary visual cortex in dementia with Lewy bodies,which is hypothesized to account for visual hallucinations, we found connectivity with this region to be unaffected. 3
57. Watson R, Colloby SJ, Blamire AM, O'Brien JT. Subcortical volume changes in dementia with Lewy bodies and Alzheimer's disease. A comparison with healthy aging. Int Psychogeriatr. 28(4):529-36, 2016 Apr. Observational-Dx One hundred participants (35 healthy controls, 32 AD, and 33 DLB) To test the hypothesis that relative to healthy aging, atrophy of the subcortical brain structures would be greater in Dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD). Significant group effects were apparent among subcortical brain volumes (F28,162 = 4.8, p < 0.001; Wilk’s lambda = 0.30, partial eta2 = 0.45), while univariate tests showed differences in all volumetric measures (p < 0.03) except in right caudate (p = 0.08). Post-hoc analyses indicated that while not significantly differentfrom AD, changes compared to healthy subjects in left caudate, bilateral putamen, left thalamus, brainstem and total subcortical grey volume were more pronounced in DLB. Significant differences between AD and DLB were confined to the bilateral hippocampus (DLB > AD, p < 0.008). 3
58. Bonifacio G, Zamboni G. Brain imaging in dementia. [Review]. Postgrad Med J. 92(1088):333-40, 2016 Jun. Review/Other-Dx N/A To review all the relatively specific findings that can be identified with different MRI and PET techniques in each of the most frequent dementing disorders. No results stated in abstract 4
59. Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 43(2):250-60, 1993 Feb. Review/Other-Dx N/A To present the criteria for diagnosis of Vascular dementia No results stated in abstract 4
60. 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
61. Heiss WD, Zimmermann-Meinzingen S. PET imaging in the differential diagnosis of vascular dementia. [Review]. J Neurol Sci. 322(1-2):268-73, 2012 Nov 15. Review/Other-Dx N/A To review positron emission tomography (PET) criteria in differential diagnosis of vascular dementia. No results stated in abstract 4
62. Brooks WM, Wesley MH, Kodituwakku PW, Garry PJ, Rosenberg GA. 1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly. Stroke. 28(10):1940-3, 1997 Oct. Observational-Dx five subjects with subcortical dementia and diffuse white matter changes; four asymptomatic elderly subjects with diffuse WMH; and five asymptomatic e To discriminate white matter hyperintensities (WMH) on MRI in patients with SAE from similar appearing changes in normal elderly The NAA/Cre and NAA/Cho ratios were reduced in the SAE group compared with the two asymptomatic groups (P<.05). NAA was decreased and Cho elevated in SAE compared with control subjects (P<.05). The average volumes of WMH in the SAE group (65.5 cm ) and in asymptomatic control subjects (59.4 cm ) were similar, and greater than those of the normal control group (4.0 cm ). 2
63. Sappey-Marinier D, Calabrese G, Hetherington HP, et al. Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities. Magn Reson Med. 26(2):313-27, 1992 Aug. Observational-Dx Seven normal volunteers, seven patients with chronic cerebral infarction or stroke and five patients with WMSH To determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities ( WMSH) using modified ISIS method for image-selected localized proton magnetic resonance spectroscopy ('H MRS) First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly ( P <0.05) increased from 0.23 +- 0.02 (mean +- SE), 0.20 +- 0.01, and 0.05 k 0.01, respectively in the normal group to 0.39 +- 0.08,0.37 +- 0.05, and 0.48 +- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +- 0.02 in the normal group to 0.64 +- 0.05 in the WMSH group. Third, in normal white matter, the concentration ofN-acetyl aspartate, choline, and lactate was estimated to 1 I .5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM. 3
64. Brundel M, Kwa VI, Bouvy WH, et al. Cerebral microbleeds are not associated with long-term cognitive outcome in patients with transient ischemic attack or minor stroke. Cerebrovasc Dis. 37(3):195-202, 2014. Observational-Dx 397 patients To examine the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitiveperformance 4 years later. The mean age was 65 ± 12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70 ± 9 vs. 64 ± 12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p < 0.05). The mean TICS score was 35.3 ± 5.9 for patients with microbleeds (n = 29) and 34.6 ± 5.2 for patients without microbleeds (n = 251); the adjusted mean difference (95% CI) was 1.69 (–0.01 to 3.38). The total IQCODEscore was 66.0 ± 10.8 for patients with microbleeds (n = 9) and 63.1 ± 12.9 for patients without microbleeds (n = 39); the adjusted mean difference was 2.43 (–7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63– 2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient ß: –0.12 (–0.23 to 0.00); p = 0.04] and with lower IQCODE score [0.51 (0.19–0.83); p = 0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12–0.65; p = 0.01). 1
65. Allen N, Berry JD, Ning H, Van Horn L, Dyer A, Lloyd-Jones DM. Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project. Circulation. 125(1):37-44, 2012 Jan 03. Review/Other-Dx 7 US Cohort studies To examine how changes in BP during middle age affect lifetime risk (LTR) for cardiovascular disease (CVD), coronary heart disease, and stroke. Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5% (95% confidence interval, 51.3–53.7) for men and 39.9% (95% confidence interval, 38.7– 41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22% to 41%, compared with individuals who had or developed hypertension by 55 years of age, 42% to 69%, suggesting a dose-response effect for the length of time at high BP levels. 4
66. Nitkunan A, Barrick TR, Charlton RA, Clark CA, Markus HS. Multimodal MRI in cerebral small vessel disease: its relationship with cognition and sensitivity to change over time. Stroke. 39(7):1999-2005, 2008 Jul. Observational-Dx 35 patients To determine which MRI parameters best correlated with cognitive function on cross-sectional analysis and which changed over a period of 1 year in patients with symptomatic sporadic small vessel disease. An executive function score correlated most strongly with diffusion tensor imaging (fractional anisotropy histogram, r= -0.640, P=0.004) and brain volume (r=0.501, P=0.034). Associations with diffusion tensor imaging were stronger than with all other MRI parameters. On multiple regression of all imaging parameters, a model that contained brain volume and fractional anisotropy, together with age, gender, and premorbid IQ, explained 74% of thevariance of the executive function score (P=0.0001). Changes in mean diffusivity and fractional anisotropy were detectable over the 1-year follow-up; in contrast, no change in other MRI parameters was detectable over this time period. 2
67. Arntzen KA, Schirmer H, Johnsen SH, Wilsgaard T, Mathiesen EB. Carotid artery plaque progression and cognitive decline: the Tromso Study 1994-2008. Eur J Neurol. 19(10):1318-24, 2012 Oct. Observational-Dx 4274 patients To assess the progression of carotid atherosclerosis in relation to cognitive test scores and to see whether carotid plaque progression could predict cognitive decline. Progression of total plaque area was associated with lower scores in the digit-symbol coding test (multivariable adjusted standardized b, -0.03; 95% CI, -0.05 to -0.00; P = 0.04) and the tapping test (b, -0.03; 95% CI, -0.06 to -0.00; P = 0.03). Similar results were seen for progression of plaque number. The average plaque scores were associated with lower scores in all cognitive tests (P-values <= 0.01). No association was found between plaque scores and cognitive decline. 3
68. Halperin JJ, Kurlan R, Schwalb JM, Cusimano MD, Gronseth G, Gloss D. Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. [Review][Erratum appears in Neurology. 2016 Feb 23;86(8):793; PMID: 26903492]. Neurology. 85(23):2063-71, 2015 Dec 08. Review/Other-Dx 21 articles To evaluate evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. Of 21 articles, we identified 3 Class I articles. 4
69. Algin O, Hakyemez B, Parlak M. Proton MR spectroscopy and white matter hyperintensities in idiopathic normal pressure hydrocephalus and other dementias. Br J Radiol. 83(993):747-52, 2010 Sep. Observational-Dx 18 patients with INPH (Group 1), 11 patients with other types of dementia (Group 2) and 20 control patients (Group 3) To evaluate the role of proton MR spectroscopy (MRS) and white matter hyperintensities (WMH) in the diagnosis of idiopathic normal-pressure hydrocephalus (INPH), predicting response to therapy and differentiating INPH from other dementias. In both Groups 1 and 2, N-acetylaspartate (NAA)/choline-NAA/creatine ratios were significantly less than in the control group (p <0.05). The WMH and MRS findings of Groups 1 and 2 demonstrated no statistically significant correlation (p >0.05). No correlation was found between the outcome of shunt operations and WMH and MRS findings (p >0.05) 2
70. Damasceno BP.. Neuroimaging in normal pressure hydrocephalus. [Review]. Dementia & Neuropsychologia. 9(4):350-355, 2015 Oct-Dec. Review/Other-Dx N/A To review the diagnosis and treatment of normal pressure hydrocephalus. No results stated in the abstract. 4
71. Chang CC, Asada H, Mimura T, Suzuki S. A prospective study of cerebral blood flow and cerebrovascular reactivity to acetazolamide in 162 patients with idiopathic normal-pressure hydrocephalus. J Neurosurg. 111(3):610-7, 2009 Sep. Observational-Dx 162 patients To assess the usefulness of the measurement of Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in determining which patients would be likely to benefit from shunt placement. One hundred forty-six patients (90.1%) responded to shunt placement (“responders”), but 16 patients (9.9%) did not (“nonresponders”). No significant difference in preoperative CBF was observed between responders and nonresponders. Preoperative CVR was significantly impaired (p < 0.0025) in responders compared with healthy controls, but not in nonresponders. Responders with the incomplete triad had a significant reduction (p < 0.001) in preoperative CVR, but not in preoperative CBF, compared with healthy controls. Responders with the complete triad had significantly lower preoperative CBF and CVR than those with the incomplete triad (p < 0.01 and p <0.05, respectively). Postoperative CBF and CVR increased significantly (p < 0.025 and p < 0.001, respectively) inresponders. 2
72. American College of Radiology. ACR Appropriateness Criteria® Radiation Dose Assessment Introduction. Available at: https://www.acr.org/-/media/ACR/Files/Appropriateness-Criteria/RadiationDoseAssessmentIntro.pdf. Review/Other-Dx N/A To provide evidence-based guidelines on exposure of patients to ionizing radiation. No abstract available. 4
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