CCCDTD5: Clinical role of neuroimaging and liquid biomarkers in patients with cognitive impairment

Abstract

Since 1989, four Canadian Consensus Conferences on the Diagnosis and Treatment of Dementia (CCCDTDs) have provided evidence-based dementia diagnostic and treatment guidelines for Canadian clinicians and researchers. We present the results from the Neuroimaging and Fluid Biomarkers Group of the 5th CCCDTD (CCCDTD5), which addressed topics chosen by the steering committee to reflect advances in the field and build on our previous guidelines. Recommendations on Imaging and Fluid Biomarker Use from this Conference cover a series of different fields. Prior structural imaging recommendations for both computerized tomography (CT) and magnetic resonance imaging (MRI) remain largely unchanged, but MRI is now more central to the evaluation than before, with suggested sequences described here. The use of visual rating scales for both atrophy and white matter anomalies is now included in our recommendations. Molecular imaging with [ 18 F]-fluorodeoxyglucose ([18F]-FDG) Positron Emisson Tomography (PET) or [ 99m Tc]hexamethylpropyleneamine oxime/ethylene cysteinate dimer ([ 99m Tc]-HMPAO/ECD) Single Photon Emission Tomography (SPECT), should now decidedly favor PET. The value of [ 18 F]-FDG PET in the assessment of neurodegenerative conditions has been established with greater certainty since the previous conference, and it has now been recognized as a useful biomarker to establish the presence of neurodegeneration by a number of professional organizations around the world. Furthermore, the role of amyloid PET has been clarified and our recommendations follow those from other groups in multiple countries. SPECT with [ 123 I]-ioflupane (DaTscan TM ) is now included as a useful study in differentiating Alzheimer's disease (AD) from Lewy body disease. Finally, liquid biomarkers are in a rapid phase of development and, could lead to a revolution in the assessment AD and other neurodegenerative conditions at a reasonable cost.We hope these guidelines will be useful for clinicians, researchers, policy makers, and the lay public, to inform a current and evidence-based approach to the use of neuroimaging and liquid biomarkers in clinical dementia evaluation and management.

Discordance and Concordance Between Cerebrospinal and [ 18 F]FDG-PET Biomarkers in Assessing Atypical and Early-Onset AD Dementia Cases

“…The study was conducted in a sample of cognitively impaired patients who meet appropriate use criteria for AD biomarker clinical evaluations. [9][10][11][12][13][14] According to our results, [ 18 F]FDG-PET and CSF biomarkers were discordant in nearly 20% of cases.…”

“…17 In this framework, Aβ and tau biomarkers are considered specific to AD, while neurodegeneration characterizes AD and other neurodegenerative diseases. 18 While appropriate use criteria exist for different AD biomarkers, [9][10][11][12][13][14] the degree to which different AD biomarkers disagree with each other in cognitively impaired patients is poorly understood.…”

Rapid recommendations

“…The CCCDTD5 recommends anatomical neuroimaging (with a preference for magnetic resonance imaging) in most situations when investigating cognitive impairment (grade 1C evidence). 14 Magnetic resonance imaging has a higher sensitivity to vascular lesions than noncontrast computed tomography (grade 2C evidence).…”

Decision making under uncertainty in the diagnosis and management of Alzheimer's Disease in primary care: A study protocol applying concepts from neuroeconomics

“…Since 1989, the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) has been generating clinical guidelines for dementia care, with the 5 th iteration published in 2020 ( 2 ). Eight topics were addressed including: (1) utility of the National Institute on Aging research framework for clinical Alzheimer's disease (AD) diagnosis ( 14 ); (2) updating diagnostic criteria for vascular cognitive impairment, and its management ( 15 ); (3) dementia case finding and detection ( 16 , 17 ); (4) neuroimaging and fluid biomarkers in diagnosis ( 18 ); (5) use of non-cognitive markers of dementia for better dementia detection ( 19 ); (6) risk reduction/prevention ( 20 ); (7) psychosocial and non-pharmacological interventions ( 21 ); and (8) deprescription of medications used to treat dementia ( 22 ). Many of these themes and recommendations can be implemented primary care.…”

“…Regarding practical management of patients with dementia—suspected of having AD—, these theories suggest that clinicians must weigh the risks and potential gains of a procedure or treatment, but also gather information regarding the “reference point” of an individual patient and their family members. New and more invasive procedures (e.g., spinal tap for the detection of biomarkers of AD—Aβ42, phosphorylated tau, and total tau—in the CSF) are now available to improve diagnostic accuracy, but not necessarily incorporated in the routine clinical practice or reimbursed appropriately ( 18 , 43 , 44 ). Similarly, new treatments (e.g., aducanumab, combination therapies with acetylcholine enhancers) are becoming available for specific patient selection, but required greater commitment than previous treatments ( 19 , 45 ).…”