Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer's Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years

Arunima Kapoor; Robert Bartha; Sandra E Black; Michael Borrie; Morris Freedman; Fuqiang Gao; Nathan Herrmann; Jennifer Mandzia; Miracle Ozzoude; Joel Ramirez; Christopher J M Scott; Sean Symons; Corinne E Fischer; Andrew Frank; Dallas Seitz; Michael Uri Wolf; Nicolaas Paul L G Verhoeff; Gary Naglie; William Reichman; Mario Masellis; Sara B Mitchell; David F Tang-Wai; Maria Carmela Tartaglia; Sanjeev Kumar; Bruce G Pollock; Tarek K Rajji; Elizabeth Finger; Stephen H Pasternak; ONDRI Investigators; Richard H Swartz

doi:10.3233/JAD-191097

Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer's Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years

J Alzheimers Dis. 2020;74(3):747-757. doi: 10.3233/JAD-191097.

Authors

Arunima Kapoor¹, Robert Bartha², Sandra E Black^{1

3

4}, Michael Borrie⁵, Morris Freedman^{4

6

7}, Fuqiang Gao³, Nathan Herrmann^{1

3

4}, Jennifer Mandzia^{8

9}, Miracle Ozzoude³, Joel Ramirez³, Christopher J M Scott³, Sean Symons¹, Corinne E Fischer¹⁰, Andrew Frank¹¹, Dallas Seitz¹², Michael Uri Wolf^{4

7}, Nicolaas Paul L G Verhoeff^{4

7}, Gary Naglie^{4

6

7}, William Reichman^{4

7}, Mario Masellis^{1

3

4}, Sara B Mitchell^{1

4}, David F Tang-Wai^{4

13}, Maria Carmela Tartaglia^{4

14}, Sanjeev Kumar^{4

15}, Bruce G Pollock^{4

15}, Tarek K Rajji^{4

15}, Elizabeth Finger^{5

8}, Stephen H Pasternak^{2

5

8}; ONDRI Investigators; Richard H Swartz^{1

3

4}

Affiliations

¹ Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
² Robarts Research Institute and the Department of Medical Biophysics, the University of Western Ontario, London, ON, Canada.
³ Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁴ University of Toronto, Toronto, ON, Canada.
⁵ Parkwood Institute, St. Joseph's Health Care Center, London, ON, Canada.
⁶ Rotman Research Institute of Baycrest Health Sciences, Toronto, ON, Canada.
⁷ Baycrest Health Sciences, Toronto, ON, Canada.
⁸ Western University, London, ON, Canada.
⁹ London Health Sciences Centre, London, ON, Canada.
¹⁰ Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute, St. Michaels Hospital, Toronto, ON, Canada.
¹¹ Elisabeth Bruyere Hospital, Ottawa, ON, Canada.
¹² Department of Psychiatry and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹³ University Health Network Memory Clinic, University of Toronto, Division of Neurology & Geriatric Medicine, Toronto, ON, Canada.
¹⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
¹⁵ Centre for Addiction and Mental Health, Toronto, ON, Canada.

Abstract

Background/objective: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer's disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies.

Methods: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies.

Results: Of 210 AD clinical trials, 105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study.

Discussion: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnosis*
Alzheimer Disease / diagnostic imaging*
Alzheimer Disease / epidemiology
Brain / diagnostic imaging*
Clinical Trials as Topic
Cognitive Dysfunction / diagnosis
Cognitive Dysfunction / diagnostic imaging
Cohort Studies
Comorbidity*
Dementia, Vascular / diagnosis
Dementia, Vascular / diagnostic imaging
Diagnosis, Differential
Female
Humans
Incidence
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Neurodegenerative Diseases / diagnosis*
Neurodegenerative Diseases / diagnostic imaging*
Neurodegenerative Diseases / epidemiology
Neuroimaging
Ontario / epidemiology
Tomography, X-Ray Computed