Abstract

Background: Determining the underlying etiology of dementia can be challenging. Computer- based Clinical Decision Support Systems (CDSS) have the potential to provide an objective comparison of data and assist clinicians.

Objectives: To assess the diagnostic impact of a CDSS, the PredictND tool, for differential diagnosis of dementia in memory clinics.

Methods: In this prospective multicenter study, we recruited 779 patients with either subjective cognitive decline (n=252), mild cognitive impairment (n=219) or any type of dementia (n=274) and followed them for minimum 12 months. Based on all available patient baseline data (demographics, neuropsychological tests, cerebrospinal fluid biomarkers, and MRI visual and computed ratings), the PredictND tool provides a comprehensive overview and analysis of the data with a likelihood index for five diagnostic groups; Alzheimer´s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and subjective cognitive decline. At baseline, a clinician defined an etiological diagnosis and confidence in the diagnosis, first without and subsequently with the PredictND tool. The follow-up diagnosis was used as the reference diagnosis.

Results: In total, 747 patients completed the follow-up visits (53% female, 69±10 years). The etiological diagnosis changed in 13% of all cases when using the PredictND tool, but the diagnostic accuracy did not change significantly. Confidence in the diagnosis, measured by a visual analogue scale (VAS, 0-100%) increased (ΔVAS=3.0%, p<0.0001), especially in correctly changed diagnoses (ΔVAS=7.2%, p=0.0011).

Conclusion: Adding the PredictND tool to the diagnostic evaluation affected the diagnosis and increased clinicians’ confidence in the diagnosis indicating that CDSSs could aid clinicians in the differential diagnosis of dementia.

Keywords: Computer-assisted diagnosis, neurodegenerative disease, CDSS, differential diagnosis, Alzheimer´s disease, Frontotemporal disease, Dementia with Lewy body, Vascular dementia.

[1]
Schoonenboom NSM, Reesink FE, Verwey NA, Kester MI, Teunissen CE, van de Ven PM, et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 78(1): 47-54. (2012).
[2]
Kapasi A, Decarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol 134: 171-86. (2017).
[3]
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, 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. Alzheimers Dement 7(3): 270-9. (2011).
[4]
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, 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. Alzheimers Dement 7(3): 263-9. (2011).
[5]
Román G, Tatemichi T, Erkinjuntti T, Cummings J, Masdeu J, Garcia J, et al. Vascular dementia:diagnostic criteria for research studies: report of the NINDS‐AIREN International Workshop. Neurology 43(2): 250-60. (1993).
[6]
Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134(9): 2456-77. (2011).
[7]
McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor J-P, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89(1): 88-100. (2017).
[8]
Sachdev P, Kalaria R. O ’brien J, Skoog I, Alladi S, Black SE, Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord 28(3): 206-18. (2014).
[9]
Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4): 535-62. (2018).
[10]
Simonsen AH, Herukka S-K, Andreasen N, Baldeiras I, Bjerke M, Blennow K, et al. Perspective recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimers Dement 13: 274-84. (2017).
[11]
Oxtoby NP, Alexander DC. Imaging plus X: multimodal models of neurodegenerative disease. Curr Opin Neurol 30(4): 371-9. (2017).
[12]
Sørensen L, Igel C, Pai A, Balas I, Anker C, Lillholm M, et al. Differential diagnosis of mild cognitive impairment and Alzheimer’s disease using structural MRI cortical thickness, hippocampal shape, hippocampal texture, and volumetry for the Alzheimer’s Disease Neuroimaging Initiative and the Australian Imaging Biomarkers and Lifestyle flagship study of ageing. Neuroimage Clin 13: 470-82. (2016).
[13]
Raamana PR, Rosen H, Miller B, Weiner MW, Wang L, Beg MF. Three-class differential diagnosis among Alzheimer disease, frontotemporal dementia, and controls. Front Neurol 5: 1-15. (2014).
[14]
Bron EE, Smits M, Van Der Flier WM, Vrenken H, Barkhof F, Scheltens P, et al. Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: the CADDementia challenge, for the Alzheimer’s Disease Neuroimaging Initiative 1. Neuroimage 111: 562-79. (2015).
[15]
Cure S, Abrams K, Belger M, Dell’angnello G, Happich M. Systematic literature review and meta-analysis of diagnostic test accuracy in alzheimer’s disease and other dementia using autopsy as standard of truth. J Allergy Clin Immunol 42(1): 169-82. (2014).
[16]
Simonsen A, Mattila J, Hejl A, Frederiksen K, Herukka S, Hallikainen M, et al. Application of the Predictad software tool to predict progression in patients with mild cognitive impairment. Dement Geriatr Cogn Disord 34(5-6): 344-50. (2012).
[17]
Koikkalainen J, Rhodius-Meester H, Tolonen A, Barkhof F, Tijms B, Lemstra AW, et al. Differential diagnosis of neurodegenerative diseases using structural MRI data. Neuroimage Clin 11: 435-49. (2016).
[18]
Tolonen A, Rhodius-meester HFM, Bruun M, Koikkalainen J, Barkhof F, Lemstra AW, et al. Data-driven differential diagnosis of dementia using multiclass disease state index classifier. Front Aging Neurosci 10: 1-11. (2018).
[19]
Van Der Flier WM, Pijnenburg YAL, Prins N, Lemstra AW, Bouwman FH, Teunissen CE, et al. Optimizing patient care and research: the amsterdam dementia cohort. J Alzheimers Dis 41: 313-27. (2014).
[20]
Van Der Flier WM, Scheltens P. Amsterdam dementia cohort: performing research to optimize care. J Alzheimers Dis 62(3): 1091-1. (2018).
[21]
McKhann GM. Clinical and pathological diagnosis of frontotemporal dementia. Arch Neurol 58(11): 1803-9. (2001).
[22]
Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51(6): 1546-54. (1998).
[23]
Gorno-Tempini M, Hillis A, Weintraub S, Kertesz A, Mendez M, Cappa S, et al. Classification of primary progressive aphasia and its variants. Neurology 76(11): 1006-14. (2011).
[24]
Mckeith I, Dickson D, Lowe J, Emre M, O’Brien J, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65(12): 1863-72. (2005).
[25]
Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6): 614-29. (2014).
[26]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3): 189-98. (1975).
[27]
Lindeboom J, Matto D. Digit series and Knox cubes as concentration tests for elderly subjects. Tijdschr Gerontol Geriatr 25: 63-8. (1994).
[28]
Reitan RM. Validity of the Trail Making Test as an indicator of organic brian damage. Percept Mot Skills 8: 271-6. (1958).
[29]
Van Der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. Normative data for the Animal, Profession and Letter M Naming verbal fluency tests for Dutch speaking participants and the effects of age, education, and sex. J Int Neuropsychol Soc 12(1): 80-9. (2006).
[30]
Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR. A brief cognitive test battery to differentiate Alzheimer ’ s disease and frontotemporal dementia. Neurology 55(11): 1613-20. (2000).
[31]
Schmidt M. Rey auditory verbal learning test: a handbook Western Psychological Services: Los Angeles, CA. (1996).
[32]
Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 39(9): 1159-65. (1989).
[33]
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17(1): 37-49. (1982).
[34]
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44(12): 2308-14. (1994).
[35]
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 140: 566-72. (1982).
[36]
Gelinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther 53(5): 471-81. (1999).
[37]
Morris JC, Weintraub S, Chui HC, Cummings J, Decarli C, Ferris S, et al. The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Dis Assoc Disord 20(4): 210-6. (2006).
[38]
Pasquier F, Leys D, Weerts JGE, Mounier-Vehier F, Barkhof F, Scheltens P. Inter-and intraobserver reproducibility of cerebral atrophy assessment on mri scans with hemispheric infarcts. Eur Neurol 36(5): 268-72. (1996).
[39]
Scheltens P, Van De Pol L. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 83(11): 1038-40. (2012).
[40]
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. Mr Signal abnormalities at 1.5-t in alzheimer dementia and normal aging. Am J Roentgenol 149(2): 351-6. (1987).
[41]
Mattila J, Koikkalainen J, Virkki A, Simonsen A, Van Gils M, Waldemar G, et al. A Disease state fingerprint for evaluation of Alzheimer’s disease. J Alzheimers Dis 27: 163-76. (2014).
[42]
Mattila J, Koikkalainen J, Virkki A, van Gils M, Lötjönen J. Design and application of a generic clinical decision support system for multiscale data. IEEE Trans Biomed Eng 59(1): 234-40. (2012).
[43]
Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11(10): 1305-19. (1992).
[44]
Rhodius-meester HFM, Koikkalainen J, Mattila J, Teunissen CE, Barkhof F, Lemstra AW, et al. Integrating biomarkers for underlying alzheimer’s disease in mild cognitive impairment in daily practice: comparison of a clinical decision support system with individual biomarkers. J Alzheimers Dis 50: 261-70. (2016).
[45]
Hall A, Muñoz-Ruiz M, Mattila J, Koikkalainen J, Tsolaki M, Mecocci P, et al. Generalizability of the disease state index prediction model for identifying patients progressing from mild cognitive impairment to Alzheimer’s disease. J Alzheimers Dis 44(1): 79-92. (2015).
[46]
Bruun M, Rhodius-meester HFM, Koikkalainen J, Baroni M, Gjerum L, Lemstra AW, et al. Evaluating combinations of diagnostic tests to discriminate different dementia types. Alzheimers Dement (Amst) Diagnosis, Assess Dis Monit 10(August): 509-18. (2018).
[47]
Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69(24): 2197-04. (2007).
[48]
White LR, Edland SD, Hemmy LS, Montine KS, Zarow C, Sonnen JA, et al. Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies. Neurology 86(11): 1000-8. (2016).
[49]
Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66(2): 200-8. (2009).
[50]
Duits FH, Prins ND, Lemstra AW, Pijnenburg YAL, Bouwman FH, Teunissen CE, et al. Diagnostic impact of CSF biomarkers for Alzheimer’s disease in a tertiary memory clinic. Alzheimers Dement 11(5): 523-32. (2015).
[51]
Ossenkoppele R, Prins ND, Pijnenburg YAL, Lemstra AW, Van Der Flier WM, Adriaanse SF, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement 9: 414-21. (2013).
[52]
Zwan MD, Bouwman FH, Konijnenberg E, Van Der Flier WM, Lammertsma AA, Verhey FRJ, et al. Diagnostic impact of [ 18 F]flutemetamol PET in early-onset dementia. Alzheimers Res Ther 9(2): 1-8. (2017).
[53]
Brunnström H, Englund E. Clinicopathological concordance in dementia diagnostics. Am J Geriatr Psychiatry 17(8): 664-70. (2009).

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy