Definitions and Diagnosis - PowerPoint Presentation

Definitions and Diagnosis Alzheimer’s Disease (AD)

Definitions

What is dementia? The word dementia comes from the Latin demens meaning ‘without mind’ 1 Dementia is a syndrome that can be caused by a variety of diseases and by injuries to the brain 2Dementia is characterized by deterioration of memory and intellectual abilities, and impaired functioning2Eventually, people with dementia are not able to live independently, and increasing nursing care is required2The DSM-V has coined the term major neurocognitive disorder as an alternative to dementia, and does not require memory for this syndrome to be diagnosed 1. McKeith & Fairbairn. In: Cantley ( ed );2001; 2. WHO. Dementia. Factsheet No. 362, 2016

Age-specific prevalence of dementia Patterns of age-specific prevalence of dementia are similar across worldwide regions, but appear to vary substantially among the oldest age group (≥90 years)2-5 1. Winblad et al. Lancet Neurol 2016;15:455–532; 2. Prince et al. Alzheimers Dement 2013;9(1):63–75; 3. Ferri et al. Lancet 2005;366(9503):2112–2117; 4. Russ et al. Int J Epidemiol 2012;41(4):1012–1032; 5. Wu et al. PLoS One 2013;8(6):e66252

Main types of dementia DLB=dementia with Lewy bodies; FTD= fronto -temporal dementia; VaD =vascular dementia Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; Alzheimer’s Society. Factsheet 403LP, 2016 Type of Dementia AD DLB VaD FTD Proportion of demantia60-80%10-15%~10%~10%

What is Alzheimer’s disease? AD is the most common cause of dementia 1 Cognitive impairment 1 Functional impairment 1 Behavioral symptoms 1 AD=Alzheimer’s disease; MMSE=Mini Mental State Examination 1. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 2. Bird. In: Pagon et al. (eds). GeneReviews® [Internet]. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1161/6MILDMODERATESEVERE 8–10 years 2 AD is a progressive disease MMSE 27 MMSE 24 MMSE 13

Diagnosis , Signs and Symptoms

Diagnosis of Alzheimer’s disease A definitive pathological diagnosis of AD occurs only at autopsy 1 In practice, AD can be clinically diagnosed by: 1,2 Medical history from the patient and, separately, from an informant who knows the patientClinical signs and symptoms Neuropsychological testsPerform confirmatory laboratory tests and imaging for evidence of biomarkers1,2The diagnosis is a process of recognizing and accounting for the decline from the individual’s previous level of functioning2 Gauthier & Ballard. Management of dementia. Informa Heathcare , 2nd edition 2009; McKhann et al. Alzheimers Dement 2011;7(11):263–269

Examples of symptoms of Alzheimer’s disease ADL=activity of daily living 1. Joubert et al. In: Gauthier ( ed );2007; 2. Rainville et al. In: Gauthier ( ed );2007 3. Alzheimer’s Association. Alzheimers Dement 2016;12(4):459–509; 4. Gélinas et al. In: Gauthier (ed);2007; 5. Teng & Cummings. In: Gauthier (ed);2007 Cognitive 1-3 Memory loss Impaired spatial and temporal orientationLanguage disturbanceAgnosiaFunctional5Reduced ability to carry out ADLs, for example: DressingHandling money Personal hygiene Neuropsychiatric 4 Mood disturbances Agitation Aggression Wandering

Hypothetical model for the pathological–clinical continuum of Alzheimer’s disease MCI=mild cognitive impairment Sperling et al. Alzheimers Dement 2011;7(3):280–292

Conclusion AD is a complex neurodegenerative disease with multifactorial etiology involving multiple neurotransmitter systems Due to the aging population, there is a growing number of people who are living with dementia and AD Numerous putative risk and protective factors have been proposed – genetic and environmental factors all play their part Age is the most important risk factor for AD; the prevalence of AD is estimated to double with every 5-year increment in age, after 65 years AD has a large impact on society – in terms of impaired abilities and quality of life, healthcare costs, caregiver burden, lost earnings, and premature deathsEfforts must continue to focus on improving the symptoms of patients with AD, such that they can retain a level of functioning, and retain their independence for longer

The diagnosis of AD

The diagnosis of AD AD is characterized by progressively worsening dementia in middle or late life. 1 In clinical practice, diagnosis of dementia (or neurocognitive disorder) is a key part of the AD diagnostic process. 2,3 There are many causes of dementia, however, and the clinical diagnosis of AD also requires that other potential types of dementia be ruled out. 2,3Historically, dementia could only be definitively attributed to AD after the patient had died, using pathological evidence obtained from an autopsy.1,4 However, with the discovery and validation of new biomarkers for AD, in vivo diagnoses have become a reality in research settings (though not yet in clinical practice). 2,4,5 1. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422

The diagnosis of AD AD is characterized by progressively worsening dementia in middle or late life. 1 In clinical practice, diagnosis of dementia (or neurocognitive disorder) is a key part of the AD diagnostic process. 2,3 There are many causes of dementia, however, and the clinical diagnosis of AD also requires that other potential types of dementia be ruled out. 2,3Historically, dementia could only be definitively attributed to AD after the patient had died, using pathological evidence obtained from an autopsy.1,4 However, with the discovery and validation of new biomarkers for AD, in vivo diagnoses have become a reality in research settings (though not yet in clinical practice). 2,4,5 A diagnosis of AD can be confirmed post-mortem by histopathological evidence of nerve cell degeneration in specific parts of the brain, and the presence of neuritic plaques and neurofibrillary tangles1.1. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422

The diagnosis of AD AD is characterized by progressively worsening dementia in middle or late life. 1 In clinical practice, diagnosis of dementia (or neurocognitive disorder) is a key part of the AD diagnostic process. 2,3 There are many causes of dementia, however, and the clinical diagnosis of AD also requires that other potential types of dementia be ruled out. 2,3Historically, dementia could only be definitively attributed to AD after the patient had died, using pathological evidence obtained from an autopsy.1,4 However, with the discovery and validation of new biomarkers for AD, in vivo diagnoses have become a reality in research settings (though not yet in clinical practice). 2,4,5 The most widely investigated biomarkers for AD fall into two classes: 2,5 biomarkers of amyloid-beta protein depositionbiomarkers of downstream neuronal degeneration or injury (such as elevated tau, decreased brain metabolism, and brain atrophy).In addition, the presence of an autosomal-dominant genetic mutation for AD – in amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 ( PSEN2 ) – is a diagnostic marker of the disease. 5 1. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422

The diagnosis of AD 1. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422 In clinical practice, patients are diagnosed with ‘probable AD’ (or ‘possible AD’ if the evidence is less conclusive). 2,3 Diagnoses of dementia and its subtypes are usually made based on:6,7medical history from the patient, and collateral history from an appropriate informantcognitive and mental state examination (using a standardized assessment scale)physical examination and laboratory tests (to exclude comorbid conditions that may be impairing cognitive function)review of medication (to identify any drugs that may be impairing cognitive function)imaging techniques (to identify dementia subtypes)other procedures.

The diagnosis of AD In clinical practice, patients are diagnosed with ‘probable AD’ (or ‘possible AD’ if the evidence is less conclusive). 2,3 Diagnoses of dementia and its subtypes are usually made based on: 6,7 medical history from the patient, and collateral history from an appropriate informant cognitive and mental state examination (using a standardized assessment scale)physical examination and laboratory tests (to exclude comorbid conditions that may be impairing cognitive function)review of medication (to identify any drugs that may be impairing cognitive function) imaging techniques (to identify dementia subtypes) other procedures .Imaging techniques useful for differential diagnosis include:6magnetic resonance imaging (MRI) or computed tomography (CT) to assist with early diagnosis and to detect subcortical vascular changessingle-photon emission computed tomography (SPECT) or positron emission tomography (PET) to help to differentiate AD from vascular dementia and frontotemporal dementia.1. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422

The diagnosis of AD In clinical practice, patients are diagnosed with ‘probable AD’ (or ‘possible AD’ if the evidence is less conclusive). 2,3 Diagnoses of dementia and its subtypes are usually made based on: 6,7 medical history from the patient, and collateral history from an appropriate informant cognitive and mental state examination (using a standardized assessment scale)physical examination and laboratory tests (to exclude comorbid conditions that may be impairing cognitive function)review of medication (to identify any drugs that may be impairing cognitive function) imaging techniques (to identify dementia subtypes) other procedures . For example, cerebrospinal fluid (CSF) examination can be used to identify underlying Alzheimer’s pathology,5 and may also be appropriate if Creutzfeldt–Jakob disease (CJD) or other forms of rapidly progressive dementia are suspected.6Electroencephalography (EEG) should be considered in cases of suspected delirium, frontotemporal dementia, CJD, or seizure disorder.61. McKhann et al. Neurology 1984;34(7):939–944; 2. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 3. APA. DSM-5. 2013; 4. Scheltens et al. Lancet 2016;388(10043):505–517; 5. Dubois et al. Lancet Neurol 2014;13(6):614–629;6. NCCMH. NICE clinical guideline 42. 2006; 7. Scott & Barrett. Expert Rev Neurother 2007;7(4):407–422

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use Summary of National Institute on Aging – Alzheimer’s Association (NIA-AA) criteria for all-cause dementia 1 Cognitive or behavioral symptoms that: interfere with the ability to function at work or at usual activities represent a decline from previous levels of functioning and performing are not explained by delirium or major psychiatric disorder. Cognitive impairment is detected and diagnosed based on patient history/interview with an informant, and objective cognitive assessment. Cognitive or behavioral impairment in at least two of the following domains: ability to acquire and remember new information; reasoning and handling of complex tasks; visuospatial abilities; language functions; changes in personality, behavior, or comportment. APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD Diagnostic criteria in common useSummary of NIA-AA criteria for probable AD1The criteria are met for dementia.Gradual onset over months to years.History of worsening of cognition.Initial and most prominent cognitive deficits in one of the following categories: amnestic (learning and recall); non-amnestic (language, visuospatial, or executive dysfunction). No evidence of another concurrent neurological disease, non-neurological comorbidity, or use of medication that could have a substantial effect on cognition. APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization NIA-AA Dementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization Summary of Diagnostic and Statistical Manual of Mental Disorders, 5 th edition (DSM-5) criteria for major/mild neurocognitive disorder 2 Evidence of cognitive decline in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual–motor, or social cognition), based on: concern of the patient, informant, or clinician a standardized assessment scale. Major neurocognitive disorder: the cognitive deficits interfere with independence in everyday activities. Mild neurocognitive disorder: the cognitive deficits do not interfere with independence in everyday activities. The cognitive deficits do not occur exclusively in the context of delirium. The cognitive deficits are not better explained by another mental disorder .

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization Summary of DSM-5 criteria for probable AD 2 The criteria are met for major or mild neurocognitive disorder. Insidious onset and gradual progression of impairment in one or more cognitive domains. Either: evidence of a causative AD genetic mutation from family history or genetic testing decline in memory and learning, and in at least one other cognitive domain (based on detailed history or serial neuropsychological testing); steadily progressive, gradual decline in cognition, without extended plateaus; and no evidence of another neurological, mental, or systemic disease or condition likely contributing to cognitive decline.

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization Summary of International Classification of Diseases, 10 th revision (ICD-10) criteria for dementia 3 Evidence of a decline in memory (especially in the learning of new information), and in other cognitive abilities characterized by deterioration in judgement and thinking, such as planning and organizing, and in the general processing of information. The decline should be objectively verified by obtaining a reliable history from an informant, supplemented, if possible, by neuropsychological tests or quantified cognitive assessments. Decline present for at least 6 months for a confident clinical diagnosis. Preserved awareness of the environment (i.e., no delirium). A decline in emotional control or motivation, or a change in social behavior manifest as emotional lability, irritability, apathy, or coarsening of social behavior .

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization Summary of ICD-10 criteria for dementia in AD 3 The criteria are met for dementia. There is no evidence from the history, physical examination or special investigations of any other possible cause of dementia, a systemic disorder, or alcohol- or drug-abuse.

Diagnostic criteria for AD To standardize the diagnostic process, several medical organizations have created diagnostic criteria for AD. In clinical practice, diagnosis of dementia (or neurocognitive disorder) is required prior to diagnosis of probable AD. 1-3 In a research setting, the classification of probable AD is no longer needed because Alzheimer’s pathology can be identified in vivo . 41. McKhann et al. Alzheimers Dement 2011;7(3):263–269; 2. APA. DSM-5. 2013; 3. WHO. Pocket Guide to the ICD-10 Classification of Mental and Behavioural Disorders. 1994; 4. Dubois et al. Lancet Neurol 2014;13(6):614–629For use in clinical practice and research For use in research only IWG-2 AD NIA-AADementia Probable AD APA DSM-5 Neurocognitive disorder Probable AD WHO ICD-10 Dementia Dementia in AD Diagnostic criteria in common use APA= American Psychiatric Association; IWG=International Working Group; NIA-AA=National Institute on Aging – Alzheimer’s Association; WHO=World Health Organization Summary of International Working Group revised criteria (IWG-2) for AD 4 A plus B at any stage. A. Specific clinical phenotype: early and significant episodic memory impairment that includes the following features: gradual and progressive change in memory function reported by patient or informant over more than 6 months objective evidence of an amnestic syndrome of the hippocampal type, based on significantly impaired performance on an episodic memory test with established specificity for AD. B. In vivo evidence of Alzheimer’s pathology (one of the following): decreased amyloid-beta together with increased tau in CSF increased tracer retention on amyloid PET AD autosomal-dominant mutation present (in APP, PSEN1 , or PSEN2 ).

Key points Historically, a definitive diagnosis of AD could only be obtained by autopsy. New biomarkers allow in vivo diagnoses of AD in research settings. In clinical practice, patients are diagnosed with ‘probable AD’ based on cognitive assessment, laboratory tests, and imaging techniques, among other procedures. Diagnosis of AD also requires that other potential types of dementia are ruled out.Medical organizations, including the APA, NIA-AA, and WHO, have created diagnostic criteria for AD for use in clinical practice or research. The IWG-2 research criteria for AD provide a more definitive diagnosis of AD based on episodic memory impairment plus biomarker evidence.

Examples of Scales in Alzheimer’s Disease

Mini–Mental State Examination (MMSE) Validity/reliability Concept Items Scoring Practicalities A measure of cognitive ability. 1. Folstein et al. J Psychiat Res 1975;12(3):189–198; 2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement: Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan. Ther Adv Neurol Disord 2012;5(6):349–358

Mini–Mental State Examination (MMSE) A measure of cognitive ability. The MMSE is an objective assessment of orientation, registration, attention and calculation, recall, language, and praxis (the performance of an action). 1 Part of the test is verbal, and part involves reading, writing and drawing. 1The MMSE was designed to screen for cognitive impairment, and is less suitable for tracking the progression of AD. 2,3 In AD clinical trials, the MMSE is widely used to screen for patients. Validity/reliability Concept Items Scoring Practicalities 1. Folstein et al. J Psychiat Res 1975;12(3):189–198;2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement : Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan. Ther Adv Neurol Disord 2012;5(6):349–358

Mini–Mental State Examination (MMSE) Item (points available) Orientation What is the: year, season, date, day, month? (5) Where are we: state, county, town, hospital, floor? (5) Registration Name three objects: one second to say each. Then ask the patient to name all 3 after you have said them. Give 1 point for each correct answer. Then repeat them until the patient learns all 3. Count the number of trials and record. (3) Attention and calculation Serial 7s (starting at 100, the patient is asked to count backwards in intervals of seven; 100, 93, 86, and so on). 1 point for each correct answer. Stop after five answers. Alternatively, spell “world” backwards. (5) Recall Ask for the three objects repeated above. Give 1 point for each correct answer. (3) Language Show the patient two simple objects, such as a wristwatch and a pencil, and ask the patient to name them. (2) Repeat the phrase: “No ifs, ands or buts.” (1) Follow a 3-stage command: “Take the paper in your right hand, fold it in half, and put it on the floor.” (3) Read and obey the following: “Close your eyes.” (1) Write a sentence (must contain a noun and a verb). (1) Copy a picture (intersecting pentagons). (1) The MMSE 1 A measure of cognitive ability. Validity/reliability Concept Items Scoring Practicalities 1. Folstein et al. J Psychiat Res 1975;12(3):189–198; 2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement : Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan . Ther Adv Neurol Disord 2012;5(6):349–358

Mini–Mental State Examination (MMSE) The patient scores points for each correct answer/completed task. 1 In total, MMSE score ranges from 0 (worst) to 30 (best ).1MMSE cut-off scores can be used to distinguish between the mild (20–26 points), moderate (10–19 points), and severe (<10 points) stages of AD (other cut-offs also exist).4,5 A measure of cognitive ability. Validity/reliability Concept Items Scoring Practicalities 1. Folstein et al. J Psychiat Res 1975;12(3):189–198;2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement : Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan . Ther Adv Neurol Disord 2012;5(6):349–358

Mini–Mental State Examination (MMSE) The MMSE is the most widely used scale in dementia due to its simplicity and practicality. 2,6 The test takes 5–10 minutes to administer. 1 As it is an objective test, the MMSE can be administered to the patient by any interviewer, such as a psychiatric resident, nurse, or volunteer.1A measure of cognitive ability. Validity/reliability Concept Items Scoring Practicalities 1. Folstein et al. J Psychiat Res 1975;12(3):189–198;2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement : Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan . Ther Adv Neurol Disord 2012;5(6):349–358

Mini–Mental State Examination (MMSE) The MMSE has high inter-rater reliability and high test–retest reliability among patients with various conditions. 1 The MMSE has high levels of sensitivity to moderate-to-severe cognitive impairment, but lacks sensitivity to mild cognitive impairment, failing to adequately discriminate patients with mild AD from healthy people.3The MMSE correlates well with other cognitive rating scales.1,3 A measure of cognitive ability. Validity/reliability Concept Items Scoring Practicalities 1. Folstein et al. J Psychiat Res 1975;12(3):189–198;2. Gauthier & Ballard. Management of Dementia. 2009; 3. Tombaugh & McIntyre. J Am Geriatr Soc 1992;40(9):922–935; 4. Maher-Edwards et al. Alzheimers Dement : Transl Res Clin Interven 2015;1(1):23–36; 5. ClinicalTrials.gov; 6. Sheehan. Ther Adv Neurol Disord 2012;5(6):349–358

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) 1. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364 ; 2 . Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396; 5. Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items Scoring Practicalities A measure of cognitive ability.

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) The ADAS-Cog consists of 11 items evaluating orientation, memory, language, and praxis in AD. 1 It comprises various objective cognitive tasks.1ADAS-Cog is suited for the assessment of mild-to-moderate stages of AD.1,2 1. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364 ; 2 . Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396; 5. Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items ScoringPracticalities A measure of cognitive ability.

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) Spoken language ability Comprehension of spoken language Recall of test instructions Word-finding difficulty Following commands Naming: objects, fingers Constructions: drawing geometric forms Ideational praxis (sending a letter) Orientation (location, date) Word recall Word recognition ADAS-Cog items 1,3 1. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364 ; 2 . Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396 ; 5 . Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items Scoring Practicalities A measure of cognitive ability.

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) Items 1–8 are rated from 0 (no impairment) to 5 (severe impairment ). 1,3 Items 9, 10 and 11 are rated according to the number of errors made, with a maximum score of 8, 10, and 12, respectively.1,3In total, the ADAS-Cog score ranges from 0 (no impairment) to 70 (severe impairment).1,3Untreated patients with moderate AD show an increase in ADAS-Cog score of approximately 9–11 points per year. 4 1. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364 ; 2. Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396; 5. Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items Scoring Practicalities A measure of cognitive ability.

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) The ADAS-Cog is administered to the patient by a trained rater. 1,2 It takes approximately 30–45 minutes to administer.51. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364; 2. Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396 ; 5. Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items ScoringPracticalities A measure of cognitive ability.

Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) The ADAS-Cog has demonstrated validity, based on the ability to measure increased dysfunction in AD over 12 months, and correlations with several other dementia rating scales. 1 The ADAS-Cog has high inter-rater reliability and high test–retest reliability among patients with AD.11. Rosen et al. Am J Psychiatry 1984;141(11):1356–1364 ; 2 . Gauthier & Ballard. Management of Dementia. 2009; 3. ADAS – Administration Manual for the Alzheimer’s Disease Assessment Scale. 1994; 4. Stern et al. Am J Psychiatry 1994;151(3):390–396; 5. Skinner et al. Brain Imaging Behav 2012;6(4):489–501 Validity/reliability Concept Items ScoringPracticalities A measure of cognitive ability.

Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S33–S39; 2. Robert et al. Alzheimers Res Ther 2010;2(4):24;3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory Validity/reliabilityConcept Items Scoring Practicalities A measure of functional ability (activities of daily living).

The ADCS-ADL was designed to assess patients’ ability to complete activities relevant to elderly individuals. 1 It is a subjective assessment, with the patient rated by an informant, based on their performance over the previous 4 weeks. 1 The ADCS-ADL originally comprised 27 items, appropriate to all stages of AD.1 A 23-item version (ADCS-ADL23) focuses on complex items, such as reading, pastime activities, and household chores, and is appropriate for the assessment of mild to moderate AD. 2 There is also a 19-item version of the scale suitable for the assessment of severe AD (the ADCS-ADL19).2Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 2):S33–S39;2. Robert et al. Alzheimers Res Ther 2010;2(4):24;3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory Validity/reliability Concept Items Scoring Practicalities A measure of functional ability (activities of daily living).

Item (score range: worst–best) 1. Eats (0–3) 12. Obtains beverage (0–3) 2. Walks (0–3) 13. Makes meal or snack (0–4) 3. Uses toilet (0–3) 14. Disposes of litter (0–3) 4. Bathes (0–3) 15. Travels beyond home (0–4) 5. Grooms (0–3) 16. Goes shopping (0–4) 6A. Selects clothes (0–3) 17. Keeps appointments (0–3) 6B. Dresses (0–4) 18. Can be left alone (0–3) 7. Uses telephone (0–5) 19. Discusses current events (0–3) 8. Watches television (0–3) 20. Reads (0–2) 9. Conversation (0–3) 21. Writes (0–3) 10. Clears table (0–3) 22. Pastimes/hobbies/games (0–3) 11. Finds belongings (0–3) 23. Uses household appliances (0–4) ADCS-ADL 23 items 3 Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S33–S39; 2. Robert et al. Alzheimers Res Ther 2010;2(4):24; 3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory Validity/reliability Concept Items Scoring Practicalities A measure of functional ability (activities of daily living).

Each item has descriptions of performance levels and corresponding scores; the informant is asked to choose the most accurate description of the patient’s performance during the past 4 weeks. 1 The ADCS-ADL 23 Total score ranges from 0 (worst) to 78 (best ).2Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S33–S39;2. Robert et al. Alzheimers Res Ther 2010;2(4):24;3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory Validity/reliabilityConcept Items Scoring Practicalities A measure of functional ability (activities of daily living).

The ADCS-ADL 23 takes about 20 minutes to administer. 2 Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S33–S39;2. Robert et al. Alzheimers Res Ther 2010;2(4):24;3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory Validity/reliabilityConcept Items Scoring Practicalities A measure of functional ability (activities of daily living).

Validity of the ADCS-ADL has been demonstrated, since all of the original 27 ADCS-ADL items correlate with the MMSE in AD (i.e., they correlate with the extent of cognitive impairment ). 1 In addition, the items capture decline in performance among patients with AD over 12 months. 1Individual ADCS-ADL items have moderate-to-very-good test–retest reliability.1Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) 1. Galasko et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S33–S39;2. Robert et al. Alzheimers Res Ther 2010;2(4):24;3. Alzheimer’s Disease Cooperative Study (ADCS). Activities of Daily Living Inventory A measure of functional ability (activities of daily living).Validity/reliability Concept Items Scoring Practicalities

Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC) A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S22–S32; 2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437Validity/reliabilityConcept Items Scoring Practicalities

The ADCS-CGIC assesses a patient’s overall change in clinical status from baseline in a clinical trial. 1 More detailed and complex scales can detect smaller changes, but these are not necessarily relevant to the patient. 1 Rather than measuring ‘any’ change, this scale is designed to measure ‘clinically meaningful’ change.1Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC) A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S22–S32;2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437Validity/reliability Concept Items Scoring Practicalities

The ADCS-CGIC consists of: 1,2 a guided baseline interview with the patient, and with an informant (typically a spouse or child) to serve as a reference for future change ratings; the interview covers 15 topics within the domains of cognition, behavior, and social and daily functioning a guided follow-up interview with the patient, and separately with the informant, using a similar set of forms. The rater can use any source to make the baseline assessment, including the interview responses; however, for the follow-up assessment, the clinician must make an assessment of change based only on the patient and informant interviews.1A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S22–S32;2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437Validity/reliability Concept Items Scoring Practicalities Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC)

The ADCS-CGIC is scored from 1 to 7 as follows: 1 Marked improvement Moderate improvement Minimal improvement No changeMinimal worseningModerate worseningMarked worsening Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC) A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 2):S22–S32;2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437 Validity/reliability Concept Items Scoring Practicalities

The ADCS-CGIC is a clinician-rated scale, comprising semi-structured interviews with the patient and an informant. 1 It takes roughly 20 minutes to administer the follow-up interview. 1 Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC)A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S22–S32;2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437Validity/reliability Concept Items Scoring Practicalities

The validity of the ADCS-CGIC has been demonstrated by its ability to show the deterioration of untreated AD patients over 12 months; it also shows modest correlation with other dementia scales over 12 months. 1 The ADCS-CGIC has good test–retest reliability, 1 but, depending on how it is tested, the inter-rater reliability of clinician-interview based impression of change scales ranges from poor to acceptable.3Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC) A measure of global change . 1. Schneider et al. Alzheimer Dis Assoc Disord 1997;11( Suppl 2):S22–S32;2. Reisberg et al. Alzheimer Dis Assoc Disord 1997;11(Suppl 3):8–18;3. Quinn et al. Neurology 2002;58(3):433–437Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory ( NPI) A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory (NPI) The NPI assesses the frequency and severity of a patient’s behavioral disturbances, in 12 domains, based on a caregiver interview. 1 For each domain, the NPI also assesses the subjective amount of caregiver burden.1The NPI can be used across various neurological disorders.2 A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory (NPI) Hallucinations Delusions Agitation/aggression Dysphoria/depression Anxiety Irritability Disinhibition Euphoria Apathy Aberrant motor behavior Sleep and night-time behavior change Appetite and eating change NPI behavioral domains 2 A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory (NPI) Each domain is scored for frequency, severity, and associated caregiver distress. 2 Frequency is rated on a 4-point scale, from 1 (rarely) to 4 (very often ).1,2 Severity is rated on a 3-point scale, from 1 (mild) to 3 (severe).1,2 Frequency and severity scores are multiplied, such that each domain is scored from 1 to 12.1,3 If a symptom is absent, it is scored 0.Caregiver distress, based on the response to “how emotionally distressing do you find this behavior?”, is rated on a 6-point scale, from 0 (not at all) to 5 (very severely or extremely).2The NPI Total score for frequency and severity ratings is the sum of the 12 domain scores, ranging from 0 (best) to 144 (worst).1The total score for caregiver distress ranges from 0 (best) to 60 (worst).2 A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory (NPI) The NPI is administered to the patient’s caregiver by a clinician. 3 The caregiver is someone who has daily contact with the patient, usually a family member involved in their daily care.2,3 The clinician reads from a script, and the caregiver rates the patient.2To minimize administration time, screening questions are used to determine which symptoms are present, and only those symptoms that are present are then rated.2 For caregivers of patients with little psychopathology, an older, 10-item version of interview can be completed in 7–10 minutes.3 A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Neuropsychiatric Inventory (NPI) NPI scores correlate with relevant behavioral items on other assessment scales. 1,3 The NPI has high inter-rater reliability in dementia, and good test–retest reliability for frequency and severity over 3 weeks.1 A measure of behavioral disturbances. 1. Cummings. Neurology 1997;48( Suppl 6):S10–S16; 2. npiTEST.net ; 3. Cummings et al. Neurology 1994;44(12):2308–2314 Validity/reliability Concept Items Scoring Practicalities

Key points The MMSE is an objective assessment of cognitive ability, often used as a screening tool in clinical trials in AD. The ADAS-Cog is a more comprehensive assessment of cognitive ability than the MMSE, which can be used to track patient deterioration. The ADCS-ADL is an informant-rated measure of ability to carry out ADLs. The ADCS-CGIC is a clinician-rated measure of a patient’s overall clinical change from baseline, based on interviews with the patient and an informant. The NPI measures the frequency and severity of a patient’s behavioral disturbances, rated by a caregiver .

Scales to assess pharmaco -economic outcomes

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) A measure of health-related quality of life ( HRQoL ). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe . EQ-5D-3L User Guide. 2015; 3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4. Orgeta et al. Qual Life Res 2015;24(2):315–324Validity/reliabilityConcept Items Scoring Practicalities

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) The EQ-5D-3L scale assesses a patient’s HRQoL: 1,2 in five different domains or dimensions (5D) over three levels of perceived severity (3L). In addition, patients rate their overall health on a vertical, visual analogue scale (VAS).2 A measure of health-related quality of life ( HRQoL ). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe . EQ-5D-3L User Guide. 2015; 3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4 . Orgeta et al. Qual Life Res 2015;24(2):315–324 Validity/reliability Concept Items Scoring Practicalities

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) The five dimensions of the EQ-5D-3L are: 2 Mobility Self-careUsual activitiesPain/discomfort Anxiety/depression For example, for mobility, the patient is asked, “Please select the ONE box that best describes your health TODAY ”.2I have no problems in walking about.I have some problems in walking about.I am confined to bed.The VAS endpoints are labelled ‘Best imaginable health state’ and ‘Worst imaginable health state’.2 A measure of health-related quality of life (HRQoL). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe . EQ-5D-3L User Guide. 2015; 3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4 . Orgeta et al. Qual Life Res 2015;24(2):315–324 Validity/reliability Concept Items Scoring Practicalities

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) Each of the five dimensions is scored from 1 to 3, where 1=no problems, 2=some problems, and 3=extreme problems. 2 The dimension scores can be grouped to form a ‘health state’; for example, 21312 indicates some problems with mobility, no problems with self-care, being unable to perform usual activities, no pain or discomfort, and moderate anxiety or depression. 2In addition, the dimension scores can be weighted and combined to form a single ‘summary index’, with a maximum score of 1 (best health state).2The VAS for overall health is scored from 0 (worst) to 100 (best ).2 A measure of health-related quality of life (HRQoL). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe . EQ-5D-3L User Guide. 2015; 3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4 . Orgeta et al. Qual Life Res 2015;24(2):315–324 Validity/reliability Concept Items Scoring Practicalities

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) The EQ-5D-3L is a patient-rated scale; a proxy version (i.e., informant-rated) is also available. 2 The EQ-5D-3L is generic, rather than specific to AD.2Patients rate their health as it is ‘today’.2It takes just a few minutes to administer.2 A measure of health-related quality of life ( HRQoL ). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe. EQ-5D-3L User Guide. 2015;3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4. Orgeta et al. Qual Life Res 2015;24(2):315–324 Validity/reliability Concept Items Scoring Practicalities

European Quality of Life – 5 Dimensions (3 Levels) (EQ-5D-3L) The EQ-5D-3L has good test–retest reliability in the general population. 3 In dementia, the EQ-5D-3L has poor agreement between self and proxy (caregiver) ratings. 4A measure of health-related quality of life ( HRQoL). 1. The EuroQoL Group. Health Policy 1990;16(3):199–208; 2 . van Reenen & Oppe . EQ-5D-3L User Guide. 2015;3. van Agt et al. Soc Sci Med 1994;39(11):1537–1544; 4. Orgeta et al. Qual Life Res 2015;24(2):315–324Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690;3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) The RUD was designed for use in clinical trials to assess the level of resource usage among patients with dementia. 1 As the full RUD tool is extensive, a shortened version was created – the RUD Lite.1The RUD Lite consists of two sections: one about the caregiver (including questions about the caregiver him- or herself, and time spent caring for the patient), and one about the patient (including questions about the patient’s living arrangements and their healthcare resource usage ).1 A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690; 3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) Patient components of the RUD Lite Accommodation/long-term care Respite care Hospital care Outpatient visits Social services Home nursing care Day care Drug use (study medication) Caregiver component of the RUD Lite Informal care time (for patient) RUD Items 1 A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690; 3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) The RUD Lite is a questionnaire rather than an assessment scale, and, as such, it is not ‘scored’. Instead, individual questions of the patient component provide resource use information, such as the number of hospitalizations, and the number of nights spent in hospital. 1Regarding the caregiver component, the number of hours per day that the caregiver cares for the patient is recorded, based on a typical care day during the past month.1 This is broken down into time spent assisting with personal ADLs (such as bathing and dressing), time spent assisting with instrumental ADLs (more complex activities such as shopping and housekeeping), and time spent supervising the patient.1 A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690; 3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) The RUD Lite is a structured interview with the primary caregiver of the AD patient, or another person with knowledge of the patient’s situation. 1The questionnaire consists of two parts with similar content – one designed for use at baseline, and the other for use at follow-up.1The RUD Lite takes approximately 15 minutes to complete. A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690; 3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Resource Utilization in Dementia Lite (RUD Lite) The caregiver estimate of time spent providing care has been shown to correlate with both caregiver diaries and direct observations, thereby demonstrating its validity. 2,3 Furthermore, the validity of the questions on hospital care and the number of outpatient visits has been shown by comparison with register data.3The questions on caregiver time, hospital care, and outpatient visits have also shown high test–retest reliability.3 A measure of resource usage. 1. Wimo & Winblad . Brain Aging 2003;3(1):48–59; 2. Wimo et al. J Nutr Health Aging 2010;14(8):685–690; 3. Wimo & Nordberg. Arch Gerontol Geriatr 2007;44(1):71–81 Validity/reliability Concept Items Scoring Practicalities

Dependence scale ( DS) A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco . Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities

Dependence scale (DS) The DS was designed to assess the level of dependence among patients with dementia. 1 The scale comprises 13 questions arranged hierarchically, such that answering ‘yes’ to questions later in the sequence indicates a more severe level of dependence.1 A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco. Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities

Dependence scale (DS) Items of the Dependence Scale: 1 Does the patient need reminders or advice to manage chores, do shopping, cooking, play games, or handle money? Does the patient need help to remember important things such as appointments, recent events, or names of family or friends? Does the patient need frequent (at least once a month) help finding misplaced objects, keeping appointments, or maintaining health or safety (locking doors, taking medication)? Does the patient need household chores done for them? Does the patient need to be watched or kept company when awake? Does the patient need to be escorted when outside? Does the patient need to be accompanied when bathing or eating? Does the patient have to be dressed, washed and groomed?Does the patient have to be taken to the toilet regularly to avoid incontinence?Does the patient have to be fed?Does the patient need to be turned, moved or transferred?Does the patient wear a diaper or a catheter?Does the patient need to be tube fed? A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco . Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities

Dependence scale (DS) Items A and B are scored on a 3-point scale: 0 (no), 1 (occasionally – at least once a month), 2 (frequently – at least once a week ). 1 The remaining items (C–M) are scored 0 (no) or 1 (yes ).1A level from 0 (no dependence) to 5 (complete dependence) can be generated, based on the following criteria:1Level 0: all items scored 0 Level 1: one of A, B, or C scored 1Level 2: two of A, B, or C scored 1; one of A or B scored 2; or D scored 1 Level 3: E, F, or G scored 1 Level 4: H, I, or J scored 1 Level 5: K, L, or M scored 1Patients with AD decline by, on average, one level every 3 years.2 A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco . Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities

Dependence scale (DS) The DS is administered by a clinician to an informant who either lives with the patient, or is well informed about the patient’s day-to-day activities. 1 As a short scale of only 13 questions, the DS is relatively quick and easy to administer, taking roughly 5 minutes. 3 A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco. Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities

Dependence scale (DS) The validity of the DS was shown by its correlation with other scales of AD severity, including cognitive and behavioral scales. 1 In a longitudinal study of patient dependence in AD, the DS showed that dependency over time increased, independently of measures of global cognition.2The DS has demonstrated excellent inter-rater reliability.1 A measure of dependence. 1. Stern et al. J Gerontol 1994;49(5):M216–M222; 2. Brickman et al. Arch Neurol 2002;59(8):1304–1308; 3. Manasco . Introduction to Neurogenic Communication Disorders. 2016 Validity/reliability Concept Items Scoring Practicalities