Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia

Since 1989, four Canadian Consensus Conferences on the Diagnosis and Treatment of Dementia (CCCDTD) have provided evidence-based dementia guidelines for Canadian clinicians and researchers. We present the results of the 5th CCCDTD, which convened in October 2019, to address topics chosen by the steering committee to reflect advances in the field, and build on previous guidelines. Topics included: (1) utility of the National Institute on Aging research framework for clinical Alzheimer's disease (AD) diagnosis; (2) updating diagnostic criteria for vascular cognitive impairment, and its management; (3) dementia case finding and detection; (4) neuroimaging and fluid biomarkers in diagnosis; (5) use of non-cognitive markers of dementia for better dementia detection; (6) risk reduction/prevention; (7) psychosocial and non-pharmacological interventions; and (8) deprescription of medications used to treat dementia. We hope the guidelines are useful for clinicians, researchers, policy makers, and the lay public, to inform a current and evidence-based approach to dementia.

# Introduction
Since

# Methods
The methodology was guided by the AGREE II collaboration 5 of which 20 of the 23 criteria were met. The steering committee chose the topics for CCCDTD5 based on a needs assessment and advances in the field.
Working groups were formed, chosen by steering committee members. Overall representation was required for neurology, psychiatry, geriatric medicine, primary care, and experienced researchers in the field. Literature searches were tailored to the group needs depending on whether the recommendations were updates or de novo topics (described below).
We attempted to follow, where possible, the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system in keeping with current recommendations for the conduct of consensus conferences.A semi-structured consensus building methodology was used, based on the Delphi process.Organizations relevant to the care of people with dementia representing industry, government, international experts, and other dementia guideline organizations had been invited to appoint nonvoting delegates as observers. Online voting closed 3 days before the conference assembly, which was held in Quebec on October 3, 2019.
At the conference each topic was briefly summarized along with the results of the online voting. Recommendations requiring revision were discussed in detail followed by an anonymous vote. The same 80% threshold was required for revised recommendations. All endorsed recommendations are listed in the tables of this article, followed by GRADE of evidence and percentage endorsement in initial vote (and subsequent vote where relevant).

## Recommendations
This summary paper lists the recommendations that reached consensus. Subsequent articles written by each working group will expand on the background work and describe in more depth the clinical impact of these recommendations.

## Nia research framework for ad diagnosis
The NIA-AA Research Framework is proposing a biological definition of AD, intended for observational and interventional research, not routine clinical care.It is proposed that the diagnosis of AD is not based on the clinical consequences of the disease (ie, symptoms/signs), but on biomarkers of amyloid beta (A) deposition, pathologic tau, and neurodegeneration (ATN). The authors did emphasize that it was premature to use this research framework in general medical practice.

## Diagnosis and treatment of vci
VCI is the second most important contributor to cognitive decline and dementia, after AD. Although recent VCI diagnostic criteria have not been validated neuropathologically in large samples, they do exhibit greater reliability than older criteria.Here we provide recommendations for neuroimaging, ,11 prevention,and management of stroke and stroke risk factors including hypertension,and pharmacological management of VCI .

## Dementia case finding and detection
The goal was to use the most current evidence to provide practi- 3. Given that the presence of brain amyloid and/or tau in cognitively normal people is of uncertain significance, we discourage the use of amyloid and tau imaging without memory decline, outside of the research setting. The medical community should be clear in its discussion with patients, the media, and the general population that the presence of brain amyloid and/or tau in normal people is of unclear significance at the present time. 1A (100%) 3b. For patients with cognitive disorders in which a vascular contribution is known or suspected, antihypertensive therapy should be strongly considered for average diastolic blood pressure readings 90 mmHg and for average systolic blood pressure readings 140 mmHg. 1B (96%)
3c. In middle-aged and older persons being treated for hypertension who have associated vascular risk factors a systolic BP treatment target of <120 mmHg may be associated with a decreased risk of developing mild cognitive impairment and should be considered when deciding on the intensity of their therapy. 14 2C (83%) 4. All patients with cognitive symptoms or impairment should receive guideline-recommended treatments to prevent first-ever or recurrent stroke, as appropriate. 1B (98%)
5a. The use of aspirin is not recommended for patients with MCI or dementia who have brain imaging evidence of covert white matter lesions of presumed vascular origin without history of stroke or brain infarcts. 2C (96%)
5b. The effects of aspirin on cognitive decline in patients with MCI or dementia who have covert brain infarcts detected on neuroimaging without history of stroke has not been defined. The use of aspirin in this setting is reasonable, but the benefit is unclear. 2C (86%). Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and the N-methyl-D-aspartate (NMDA) receptor antagonist memantine may be considered for the treatment of vascular cognitive impairment in selected patients. 2B (89%)

## Ta b l e 3 dementia case finding and detection
Is there a role for screening at-risk patients without clinical concerns? In what context is assessment for dementia appropriate?
1. Cognitive testing to screen asymptomatic adults for the presence of mild cognitive impairment or dementia, including asymptomatic persons with risk factors such as family history or vascular risk factors, is not recommended. 1C (95%) 2. Primary care health professionals should be vigilant for potential symptoms of cognitive disorders in older or at-risk individuals, including but not limited to: reported cognitive symptoms by the patient or an informant, otherwise unexplained decline in instrumental activities of living, missed appointments or difficulty remembering or following instructions or taking medications, decrease in self-care, victimized by financial scams, or new onset later-life behavioral changes including new depression or anxiety (1C). If there is a clinical concern for a cognitive disorder (which may not always be shared by the patient due to anosognosia) then validated assessments of cognition, activities of daily living, and neuropsychiatric symptoms are indicated (see subsequent sections for suggestions for valid tools). 1A (95%). In persons at elevated risk for cognitive disorders (such as very advanced age, pre-existing brain diseases such as Parkinson's disease, a recent episode of delirium, or risk factors such as diabetes) it is reasonable to ask the patient (and an informant, if available) about concerns regarding memory (2C). If clinically significant memory concerns are elicited then further evaluation using validated assessments of cognition, behavior, and function is appropriate (see subsequent sections for suggestions for valid tools). 1B (98%)
What tools can be used to evaluate patients in whom cognitive decline is suspected?
1. Routine screening of asymptomatic individuals has no evidence at this point. Cognitive testing to screen asymptomatic adults for the presence of mild cognitive impairment or dementia is not recommended. 1C (95%) 2. Primary care health professionals should stay vigilant for potential early symptoms of cognitive disorders in older individuals who may be less likely to report due their lack of insight, social isolation, or sociocultural beliefs, and in older individuals with warning signs, including but not limited to: reported cognitive symptoms by the patient or an informant, otherwise unexplained decline in instrumental activities of living, missed appointments, showing up to appointments at the incorrect time or day, difficulty remembering or following instructions or taking medications, decrease in self-care, or new onset of later-life behavioral changes including new depression or anxiety (1C). If there is a clinical concern for a cognitive disorder (which may not always be shared by the patient due to their lack of insight) then validated assessments of cognition, activities of daily living, and neuropsychiatric symptoms are indicated (see subsequent sections for suggestions for valid tools). 1A (95%) (Continues)

## Ta b l e 3 (continued)
3. In persons with elevated risk for cognitive disorders or with medical conditions associated with cognitive disorders such as 21 : (a) a history of stroke or transient ischemic attack (TIA); (b) late-onset depressive disorder or a lifetime history of major depressive disorder; (c) untreated sleep apnea; (d) unstable metabolic or cardiovascular morbidity; (e) a recent episode of delirium; (f) first major psychiatric episode at an advanced age (psychosis, anxiety, depression, mania); (g) recent head injury; (h) Parkinson's disease. It is reasonable to ask the patient and an informant about concerns regarding cognition and behavior (2C). If clinically significant cognitive concerns are elicited, then further evaluation using validated assessments of cognition, behavior, and function is appropriate (see subsequent sections for suggestions for valid tools). 1B (93%). The distinction between MCI and dementia is important and is currently made on the basis of clinical assessment of cognition and function. For screening purposes, examining the complaint with the patient and a family member and proceeding with an objective assessment of cognition and functional impairment should be done. 1A (88%)
5. An objective assessment of the patient's cognitive function could be achieved by using rapid psychometric screening tools such as the Memory Impairment Screen (MIS)+ clock drawing test (CDT),the Mini-Cog,the AD8,the four item version of the MoCA (Clock-drawing, Tap-at-letter-A, Orientation, and Delayed-recall),MMSE remains the most widely used instrument, with high sensitivity and specificity for separating moderate dementia from normal cognition and is recommended in many countries. However, it lacks sensitivity for the diagnosis of mild dementia or MCI. The MoCA 31 is more sensitive to MCI than the MMSE and its use is recommended when mild cognitive impairment is suspected or in cases where there is suspicion of cognitive impairment or concern about the patient's cognitive status, and the MMSE score is in the "normal" range (24+ out of 30). 1B (93%)
7. The use of longitudinal serial cognitive assessments like the QuoCo curves 32 might help optimize accuracy for distinguishing participants with dementia from healthy controls. 1C (80%). To obtain information in addition to that provided by the other psychometric screening tools, or if the patient is unable to answer the questions on the screening tools (lack of time or uncooperative), having the caregiver complete a questionnaire for identifying a cognitive and/or functional change, such as the Ascertain Dementia 8 (AD-8) questionnaire or the Informant Questionnaire on cognitive decline in the elderly (IQCODE)is recommended. 1B (93%). Combining cognitive tests with functional screens and informant reports may improve case-finding in people with cognitive difficulties. 1A (95%). Rapid screening of functional autonomy should be completed by an objective assessment with the patient and a family member using the Pfeffer Functional Activities Questionnaire (FAQ)or the Disability Assessment for Dementia (DAD). 35 1C (89%). If a personality, behavior, or mood change has been observed, an objective assessment of the behavioral and psychological symptoms of dementia (BPSD) with the patient and a family member using the short version of the Neuropsychiatric Inventory (NPI-Q),Mild Behavioural Impairment Checklist (MBI-C)or if a mood change has been observed with the Patient Health Questionnaire-9 (PHQ). 38 1A (93%)
What important information can be gained from an informant, using which measures?
1. Due to variability in insight into cognitive, functional, and behavioral changes, report from a reliable informant is an essential component for the assessment of patients with suspected neurocognitive disorders at all settings. 1C (91%)
2. The use of standardized tools to obtain informant report on changes in cognition, function, and behavior increases the diagnostic accuracy when combined with patient-related measures and therefore is recommended. 1C (93%) 3. We recommend using one or more informant-based tools that cover cognitive, functional, and behavioral aspects. Specific tools can be selected based on the need for comprehensive assessment versus efficiency depending upon the setting. 1C (86%)
4. There is ongoing development of informant-based tools, and based on the current evidence we recommend tools that: measure informant's report of cognitive changes (eg, ECog)What instruments can be used to get more in-depth information to diagnose MCI or dementia?
In addition to neuropsychological testing (if available), we make the following recommendations with regard to the instruments available for more in-depth cognitive evaluation of MCI and dementia:
1. A number of well-validated instruments exist to help in the process of MCI or dementia diagnosis. However, diagnosis of MCI or dementia should not be solely based on an impaired result on cognitive screening tests. 1B (100%)

## Ta b l e 3 (continued)
What is the approach to those with cognitive concerns but without objective cognitive changes (ie, recommendations for subjective cognitive decline [SCD])? Functional and Ligand-Based Imaging 3a. For a patient with a diagnosis of a cognitive impairment who has undergone the recommended baseline clinical and structural brain imaging evaluation and who has been evaluated by a cognitive disorders specialist but whose underlying pathological process is still unclear, preventing adequate clinical management, an [ 18 F]-FDG PET scan is an effective and accurate tool for differential diagnosis purposes. 1A (88%)
3b. If such a patient cannot be practically referred for a FDG-PET scan, we recommend that a SPECT rCBF study be performed for differential diagnosis purposes. 1B(86%) 7. CSF analysis can also be considered in dementia patients with diagnostic uncertainty and predominance of language, visuospatial, dysexecutive, or behavioral features to rule out AD pathophysiology. 1C (78%; 100%)

## Ta b l e 5 non-cognitive markers of dementia
1a. There is strong evidence that slower gait speed is associated with future dementia, in population studies. When gait speed (cut-off gait speed below 0.8m/s) is coupled with cognitive impairment (subjective or objective) the risk is higher. We recommend testing gait speed in clinics in those patients with cognitive complaints/impairments if time/resources are available. 1B (62%, 100%) Note: Protocols on how to assess gait speed with stopwatch are available. Testing takes, on average, 3 minutes to perform. 91 1b. Dual-task gait impairment (lower speed or high cost) is associated with future incident dementia. In MCI samples, dual-task gait was shown to predict time to progression to dementia. Variability in the delivery of testing protocols is noted. We recommend that dual-task gait test may be used in specialized clinics (memory clinics) to help identify mild cognitive impairment (MCI) older adults at higher risk of progression to dementia if time/resources are available. 2B (60%, 100%) Note: Published protocols on how to assess Dual-Task Gait for dementia risk with just a stopwatch are available.
(Continues) 5b. If symptoms of hearing loss are reported, then hearing loss should be confirmed by audiometry conducted by an audiologist meeting provincial regulations for the practice of audiology. If confirmed, audiologic rehabilitation may be recommended. This rehabilitation may include behavioral counselling and techniques, and may or may not include the recommended use of a hearing aid or other device. 1A (98%).

## Ta b l e 7 psychosocial interventions
Individual Level 1. We recommend exercise (group or individual physical exercise) for people living with dementia.We cannot recommend any specific exercise duration or intensity at this time. 1B (93%) 2. Group cognitive stimulation therapy is an intervention for people with dementia which offers a range of enjoyable activities providing general stimulation for thinking, concentration, and memory usually in a social setting, such as a small group. We recommend considering group cognitive stimulation therapy for people living with mild to moderate dementia. 101-104 2B (96%)
3. Psychoeducational interventions for caregivers aim at the development of problem-focused coping strategies while psychosocial interventions address the development of emotion-focused coping strategies. These can include education, counseling, information regarding services, enhancing carer skills to provide care, problem solving, and strategy development. We recommend considering psychosocial and psychoeducational interventions for caregivers of people living with dementia.6. Deprescribing of ChEIs or memantine should occur gradually and treatment reinitiated if the individual shows clinically meaningful worsening of cognition, functioning, neuropsychiatric symptoms, or global assessment that appears to be related to cessation of therapy. 1B (98%). Dose reduction during deprescribing should follow general guidelines for deprescribing of medications with a reduction of dose by 50% every 4 weeks until the initial starting dose is obtained. After 4 weeks of treatment on the recommended starting dose, the cognitive enhancer could be discontinued. 2C (96%) 8. Cholinesterase inhibitors should not be discontinued in individuals who currently have clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized unless these symptoms appear to have been worsened by the initiation of a ChEI or an increase in ChEI dose. 2B (78%, 100%) 9. Individuals who have had a clinically meaningful reduction in neuropsychiatric symptoms (eg, psychosis) with cognitive enhancers should continue to be treated with the cognitive enhancer even if there is evidence of cognitive and functional decline. 2B (96%). Cholinesterase inhibitors and memantine should be deprescribed for individuals with mild cognitive impairment. 1B (89%)

## Use of neuroimaging and fluid biomarkers
The imaging biomarkers groups extended the previous consensus work, .

## Non-cognitive markers of dementia
Although cognitive impairment is the hallmark of AD and related dementias, non-cognitive markers may be early non-invasive biomarkers.

## Risk reduction
As dementia prevention and fluid increasingly seems plausible,CCCDTD has addressed risk reduction in this iteration. We took the approach that most dementia occurs in late life and typically has multiple causes 96,97 building on updates from a 2017 comprehensive overview of dementia prevention.We supplemented information (when present) with updates, especially focusing on Canadian data. We offer recommendations on interventions that appear to have importance both across the life course and in primary, secondary, and sometimes tertiary prevention including: (1) nutrition, (2) physical exercise, (3) hearing loss, (4) sleep, (5) cognitive training and rehabilitation, (6) social engagement and education, (7) frailty,and medications .

## Psychosocial and non-pharmacological interventions
The psychosocial and non-pharmacological interventions encompass a broad range of interventions and typically aim at improving cognition, symptoms, or well-being (including that of caregivers), or at adapting organizations and communities to the needs of people living with dementia and their caregivers. For the first time, the CCCDTD created a working group on these interventions. We synthetized published meta-analysis and reviews and provide five recommendations of both individual level and community level interventions, as both have the potential to improve outcomes for people living with dementia .

## Deprescription of medications used to treat dementia
Acknowledging that many individuals who are affected by demen- .

# Conclusions
We hope that these evidence-based recommendations will be useful to clinicians and policy makers as well as the public at large. We do appreciate that within Canada, individual jurisdictions and access to care vary, and these recommendations are intended as guidelines for clinicians to implement in their practices based on available resources. The recommendations may also be useful to professional groups in other countries, taking into account local culture and resources.

# Acknowledgments
The CCCDTD5 meeting was supported financially by the Canadian Consortium on Neurodegeneration in Aging, the Reseau des cliniques memoire du Quebec, the Reseau Quebecois de Recherche sur le Vieillissement.

## Participants
The recommendations were prepared by the following working groups: