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Table 2 Review of potential endpoints for consideration

From: Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

Domain Test example Strengths Limitations
Global Clinician Interview Based Impression of Change (with caregiver interview) Evaluates behavior, cognition and functioning; previously used in clinical trials; demonstrated sensitivity to change Relies on subjective data from caregivers
  Clinical Dementia Rating FTD-Specific version available; sensitive to change; association with biomarkers Reliance on subjective data; lengthy to administer; coarse metric
  Clinical Global Impressions Widely used in existing trials in FTD; sensitive to change; individual subscales available Reliance on subjective data
Composite Montreal Cognitive Assessment Brief screen; sensitive to change; multicultural; alternate forms; freely available Limited use in clinical trials; insufficient coverage of cognitive domains; potential for ceiling effects
  Repeatable Battery for the Assessment of Neuropsychological Status Multi-domain assessment; alternate forms available Inadequate coverage of executive functioning
  Dementia Rating Scale, 2nd Ed. Multi-domain assessment sensitive to presence of dementia; previously used in clinical trials Limited assessment of executive functioning; no alternate form
  EXAMINER Developed with FTD in mind; intended for clinical trials; customizable; specific to executive functioning; measures social cognition and behavior Actual trial performance is to be determined
  Neuropsychological Test Battery Proven trial performance; sensitive to change Relies heavily on memory functioning; no alternate forms
Executive Trail Making Test Previously used in clinical trials; extensive normative data; widely used Limited sensitivity to change in previous trials; prone to floor effects
  Stroop Test Multiple variants available; extensive normative data; previously used in clinical trials; relatively immune to ceiling effects Sensitive to practice effects; interference conditions may be prone to floor effects
  EXIT-25 Previously used in FTD trials Longer and more complicated administration than comparable alternatives
  Frontal Assessment Battery Brief, simple administration; sensitive to change; multiple language versions No alternate forms
  Clock Drawing Sensitive to executive dysfunction; simple and brief administration; many variants available Sensitivity and specificity vary as a function of version used.
Language Boston Diagnostic Aphasia Examination Sensitive to expressive and receptive language impairments; Limited use in clinical trials; limited sensitivity to speech abnormalities; no alternate forms; prone to ceiling effects
  Western Aphasia Battery Sensitive to expressive language impairments; previous use in clinical trials limited sensitivity to speech abnormalities; no alternate forms; prone to ceiling effects
  Controlled Oral Word Association Test Previously used in trials; sensitive to change Only one well-validated alternate form; culturally limited
  Boston Naming Test Widely used; extensive normative data; some use in trials Non-normal distribution of scores; no alternate forms; culturally limited
Memory California Verbal Learning Test, 2nd Ed. Provides multiple estimates of memory (including learning) and insight into executive functioning Only one alternate form; lengthy to administer; Recognition trials vulnerable to ceiling effects
  Rey Auditory Verbal Learning Test Previously used in clinical trials; provides estimates of learning, recall and recognition Recognition trials vulnerable to ceiling effects; recall trials vulnerable to floor effects
Visuospatial Functioning Judgment of Line Orientation Relatively free from practice effects; minimal demand on motor and language Vulnerable to ceiling effects; can be lengthy administration
  Figure Copy tests Insights into perception, organization and executive functioning; multiple forms Confounded by motor impairment; scoring can be complex
Behavior Neuropsychiatric Inventory Widely used in clinical trials; sensitive to change Not specific to behavioral changes associated with FTD; large standard variations; Improvements may be related to increasing apathy
  Frontal Behavior Inventory Sensitive to change; employed in existing trials Improvements may be related to increasing apathy
  Frontal Systems Behavior Examination Allows for intra-individual comparison; quantification of apathy Relies on reliable informant