Diagnostic Issues in Dementia: Neuroimaging as a Surrogate Marker of Disease

Abstract

Structural neuroimaging is a routine component of the diagnostic evaluation of dementia that is used to rule out potential causes of mental impairment, whereas functional imaging can differentiate different forms of dementia. Neuroimaging also offers promise as a surrogate marker for clinical trials, and new technologies have been developed to provide measures of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer’s disease. Combining imaging with genetic risk data will likely improve diagnostic accuracy. These new findings warrant reconsideration of current guidelines on the use of neuroimaging in diagnosis and research in dementia. (J Geriatr Psychiatry Neurol 2006;19:180-185)

Keywords

neuroimaging dementia Alzheimer’s disease mild cognitive impairment diagnosis surrogate markers

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References

Bachman DL , Wolf PA , Linn RT , et al. Incidence of dementia and probable Alzheimer’s disease in a general population: the Framingham study. Neurology 1993; 43:515-519.

Small GW , Rabins PV , Barry PP , et al. Diagnosis and treatment of Alzheimer’s disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997; 78:1363-1371.

Petersen RC , Parisi JE , Dickson DW , et al. Neuropathology of amnestic mild cognitive impairment. Arch Neurol 2006; 63: 665-672.

Petersen RC , Smith GE , Waring SC , Ivnik RJ , Tangalos EG , Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56:303-308.

Andersen K , Nielsen H , Lolk A , Andersen J , Becker I , Kragh-Sorensen P. Incidence of very mild to severe dementia and Alzheimer’s disease in Denmark: the Odense Study. Neurology 1999; 52:85-90.

National Institute on Aging . Progress Report on Alzheimer’s Disease 1996 (NIH publication no 96-4137). Bethesda, Md: National Institute on Aging; 1996.

Ernst RL , Hay JW. The U.S. economic and social costs of Alzheimer’s disease revisited. Am J Public Health 1994; 84:1261-1264.

Grundman M , Petersen RC , Ferris SH , et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol 2004; 61:59-66.

Callahan CM , Hendrie HC , Tierney WM. Documentation and evaluation of cognitive impairment in elderly primary care patients. Ann Intern Med 1995; 122:422-429.

10.

Ross GW , Abbott RD , Petrovich H , et al. Frequency and characteristics of silent dementia among elderly Japanese-American men. The Honolulu-Asia Aging Study. JAMA 1997; 277:800-805.

11.

Saunders AM , Strittmatter WJ , Schmechel D , et al. Association of apolipoprotein E allele E4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 1993; 43: 1467-1472.

12.

Corder EH , Saunders AM , Strittmatter WJ , et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261:921-923.

13.

Relkin NR , Tanzi R , Breitner J , et al. Apolipoprotein E geno-typing in Alzheimer’s disease: position statement of the National Institute on Aging/Alzheimer’s Association Working Group. Lancet 1996; 347:1091-1095.

14.

Blennow K , Skoog I.

Genetic testing for Alzheimer’s disease: how close is reality?

Curr Opin Psychiatry 1999; 112:487-493.

15.

DeCarli C , Kaye JA , Horowitz B , Rapoport S. Critical analysis of the use of computer-assisted transverse axial tomography to study human brain aging and dementia of the Alzheimer’s type. Neurology 1990; 40:872-883.

16.

Braak H , Braak E. Neuropathologic staging of Alzheimer-related changes. Acta Neuropathol 1991; 82:239-259.

17.

Laakso MP , Soininen H , Partanen K , et al. MRI of the hippocampus in Alzheimer’s disease: sensitivity, specificity, and analysis of the incorrectly classified subjects. Neurobiol Aging 1998;19:23-31.

18.

Jack CR , Petersen RC , Xu YC , et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 1999; 52:1397-1403.

19.

Silverman DHS , Small GW , Phelps ME. Clinical value of neuroimaging in the diagnosis of dementia: sensitivity and specificity of regional cerebral metabolic and other parameters for early identification of Alzheimer’s disease. Clin Positron Imaging 1999; 2:119-130.

20.

Small GW , Mazziotta JC , Collins MT , et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 1995; 273:942-947.

21.

Imamura T , Ishii K , Sasaki M , et al. Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer’s disease: a comparative study using positron emission tomography. Neurosci Lett 1997; 235:49-52.

22.

Albin RL , Minoshima S , D’Amato CJ , Frey KA , Kuhl DA , Sima AAF . Fluoro-deoxyglucose positron emission tomography in diffuse Lewy body disease. Neurology 1996; 47:462-466.

23.

Ishii K , Sakamoto S , Sasaki M , et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med 1998; 39:1975-1988.

24.

Mazziotta JC , Phelps ME , Pahl JJ , et al. Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. N Engl J Med 1987; 316:357-362.

25.

Vander Borght T , Minoshima S , Giordani B , et al. Cerebral metabolic differences in Parkinson’s and Alzheimer’s diseases matched for dementia severity. J Nucl Med 1997; 38:797-802.

26.

Silverman DHS , Small GW , Chang CY , et al. Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term clinical outcome. JAMA 2001; 286: 2120-2127.

27.

Minoshima S , Frey KA , Koeppe RA , Foster NL , Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36:1238-1248.

28.

Chételat G , Desgranges B , de la Sayette V , et al.

Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer’s disease?

Neurology 2003; 60:1374-1377.

29.

Kennedy AM , Frackowiak RSJ , Newman SK , et al. Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer’s disease. Neurosci Lett 1995; 186:17-20.

30.

Reiman EM , Caselli RJ , Yun LS , et al. Preclinical evidence of Alzheimer’s disease in persons homozygous for the ε4 allele for apolipoprotein E. N Engl J Med 1996; 334:752-758.

31.

Small GW , Ercoli LM , Silverman DHS , et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A 2000; 97:6037-6042.

32.

Reiman EM , Caselli RJ , Chen K , Alexander GE , Bandy D , Frost J. Declining brain activity in cognitively normal apolipo-protein E ε4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer’s disease. Proc Natl Acad Sci U S A 2001; 98:3334-3339.

33.

Mega MS , Cummings JL , Masterman DM , et al. Cognitive and metabolic responses to metrifonate therapy in Alzheimer’s disease. Neuropsychiatry Neuropsychol Behav Neurol 2001; 14:63-68.

34.

Bookheimer SY , Strojwas MH , Cohen MS , et al. Brain activation in older people at genetic risk for Alzheimer’s disease. N Engl J Med 2000; 343:450-456.

35.

Ashburn TT , Han H , McGuinness BF , Lansbury PT. Amyloid probes based on Congo Red distinguish between fibrils comprising different peptides. Chem Biol 1996; 3:351-358.

36.

Klunk WE , Debnath ML , Pettegrew JW. Chrysamine-G binding to Alzheimer and control brain: autopsy study of a new amyloid probe. Neurobiol Aging 1995; 16:541-548.

37.

Lovat LB , O’Brien AA , Armstrong SF , et al. Scintigraphy with 123I-serum amyloid P component in Alzheimer disease. Alzheim Dis Assoc Disord 1998; 12:208-210.

38.

Majocha RE , Reno JM , Friedland RP , VanHaight C , Lyle LR , Marotta CA. Development of a monoclonal antibody specific for beta/A4 amyloid in Alzheimer’s disease brain for application to in vivo imaging of amyloid angiopathy. J Nucl Med 1992; 33:2184-2189.

39.

Shoghi-Jadid K , Small GW , Agdeppa ED , et al. Localization of neurofibrillary tangles (NFTs) and beta-amyloid plaques (APs) in the brains of living patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2002; 10:24-35.

40.

Agdeppa ED , Kepe V , Liu J , et al. Binding characteristics of radiofluorinated 6-dialkylamino-2-napthylethylidene derivatives as PET imaging probes β-amyloid plaques in Alzheimer’s disease. J Neurosci 2001, 21:RC189-RC189.

41.

Klunk WE , Engler H , Nordberg A , et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55:306-319.

42.

Verhoeff NPLG , Wilson AA , Takeshita S , et al. In-vivo imaging of Alzheimer disease β-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 2004; 12:584-595.

43.

Small GW , Kepe V , Ercoli L , et al. FDDNP-PET scanning of cerebral amyloid and tau deposits in MCI. Paper presented at: the American Academy of Neurology Annual Meeting; April 4, 2006; San Diego, Calif.

44.

Kepe V , Cole GM , Liu J , et al. In vivo [F-18]FDDNP microPET imaging of brain β-amyloid in a transgenic rat model of Alzheimer’s disease. Alzheim Dem 2005; 1(suppl 1):S45-S45.

45.

Agdeppa ED , Kepe V , Petric A , et al. In vitro detection of (S)naproxen and ibuprofen binding to plaques in the Alzheimer’s brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl} ethylidene)malononitrile. Neuroscience 2003; 117:723-730.

46.

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.

47.

Mosconi L , Perani D , Sorbi S , Herholz K , Nacmias B , Holthoff V , et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 2004; 63:2332-2340.