Points to consider on frailty: Evaluation instruments for baseline characterisation of clinical trial populations

thinking, category fluency, delayed recall) were introduced to assess a broader range of 295 cognitive capacity and difficulty levels. More uniform administration and a refined scoring were 296 incorporated to enhance the reliability and validity of the test scores. 297 298 The 3MS test has a score range of 1–100 and takes 8-15 minutes to administer. It can provide an 299 estimated score of the MMSE, and can also be used to monitor cognitive change over time. It is more 300 sensitive than the MMSE in detecting within-individual changes over time. By now a large body of 301 literature has shown the usefulness of the 3MS test in both research and clinical studies. 302 303 Advantages: 304 305 The MMSE is an ubiquitous scale, used as a screening instrument for dementia in CNS and non CNS 306 trials. It is easy to compare among trials. It has been in use for almost 40 years, it is easy to use by 307 psychologists, clinicians, study nurses and other clinical trial staff. It explores several domains: 308 orientation, calculus, memory, delayed recall, language, praxis. The time of the assessment is short for 309 both instruments. 310 311 Limitations: 312 313 • Neither the MMSE nor the 3MS have been designed primarily as a screening instrument for 314 dementia. 315 316 • Not formally validated in most languages 317 318 • Does not quantify the response time 319 320 • Is less sensitive to executive functions (which may be significant in frail persons) 321 322 • High threshold for illiterate or pauci-literate patients 323 324 6.2. 2. Montreal Cognitive Assessment (MoCA)(54) 325 326 Developed to identify early amnestic MCI, but including executive functions particularly important when 327 studying vascular disorders (55), with patients at risk. Also, in research projects where periodic 328 cognition frailty assessment or if repetition of evaluation within 3 months is needed, the learning effect 329 should be considered. MoCA is a rapid cognitive test, available in multiple languages and easy to apply, 330 encompassing all of these aspects. In patients where cognition impairment is in the near dementia or 331 dementia range, the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) or 332 Cognitive Drug Research (CDR) could be used for classification of degree of dementia, although there 333 is evidence that the latter scale is less sensitive to short-term change and may be complicated for use 334 in clinical practice (47, 56-58) (Refer to Guideline on Alzheimer Disease). 335 336 It is recognized that a psychological component of the condition is evident and increases the 337 vulnerability of the individuals. Specific tests for assessment of depression and / or social role are not 338 being proposed, as their relation to cognitive frailty is variable as signalled above. Also their 339 assessment usually depends upon experienced clinicians. 340 341 MoCA is an easy to fill in, intuitive scale designed as a screening instrument for early detection of mild 342 cognitive impairment (MCI), it can be administered in about 10 – 15 minutes (including patient 343 intervention) by psychologists, clinicians, study nurses and other clinical trial staff. MoCA has been in 344 use for almost 10 years and is formally validated in more than 60 languages and for the blind. It 345