Assessing clinical outcomes in Alzheimer’s disease

Clinical outcomes are vital to assess a person with Alzheimer’s disease (AD) and track their progress. In this symposium, held at the 8th Congress of the European Academy of Neurology, Vienna, June 24−28 2022, Dr John Harrison (Alzheimer Center of the VUmc, Amsterdam, The Netherlands), discussed how the Clinical Dementia Rating scale is a comprehensive assessment of dementia, but content validity might be variable. Dr Temitope Farombi (Chief Tony Anenih Geriatric Center, University College Hospital, Ibadan, Nigeria), discussed use of the quick to administer Mini-Mental State Examination, and highlighted how the Identification and Intervention for Dementia in Elderly Africans measure may be more suitable in people with low formal education levels. Dr Rui Araújo (Centro Hospitalar Universitário São João, Porto, Portugal) talked about the Montreal Cognitive Assessment, which is used as a screening test. While advantages include sensitivity to early stage AD, there are high false positive rates in culturally diverse populations. Finally, Professor Ramin Nilforooshan (Dementia Research Institute, Imperial College London, UK) highlighted the use of digital biomarkers to track changes in the health of people with AD and how these may be used in the future to alert people to early health concerns in this realm.

The Clinical Dementia Rating Scale

The Clinical Dementia Rating (CDR) scale is an hour long, semi-structured interview with the patient and a caregiver. It includes assessment in six domains: memory; judgement and problem solving; orientation; home and hobbies; personal care; and community affairs, as well as having a global score.1 Scores on these domains, from 0−3 for normal to severe with a 0.5 score for ‘questionable,’ are independent of each other and level of impairment may differ between each domain.2

The Clinical Dementia Rating scale is a comprehensive, semi-structured interview

Though useful, the CDR is rarely applied in clinical practice, reported Dr Harrison, and discrepancies have been found between naïve and experienced raters regarding the severity of dementia.3 Overall, Dr Harrison concluded the while it may be useful, the CDR, in his opinion, has variable content validity, variable reliability, and modest sensitivity.

 

The Mini-Mental State Examination and Identification and Intervention for Dementia in Elderly Africans measure

Dr Farombi discussed the Mini-Mental State Examination (MMSE),4 which is often used as a quick screen in the clinic5 as it takes around 5−10 minutes to administer,6 and as a secondary endpoint in clinical trials.7 The MMSE quantitively assesses cognitive impairment severity6 and can be used to classify moderate stages of dementia.8 Assessments include of orientation, attention or calculation, registration, recall, language, comprehension, and motor skills.6 Possible total scores range from 0−30 with a score ≤23 indicating dementia.4

The MMSE is fast and easy to administer and scoring is straightforward; however, it doesn’t assess executive functioning and it may not be sensitive to subtle cognitive changes in patients with early dementia or mild cognitive impairment (MCI).4,6 Importantly, highlighted Dr Farombi, MMSE performance outcomes are affected by education level,4 and there are few local language translations.

The Identification and Intervention for Dementia in Elderly Africans is of use for people with low formal education levels

The Identification and Intervention for Dementia in Elderly Africans (IDEA) is a 10−15 minute instrument with three domains: naming, language and abstract thinking; orientation; and memory and praxis. Total score is 15 with a score ≤7 indicating major cognitive impairment. IDEA, currently validated in Tanzania and Nigeria,9 shows good inter-rater reliability and internal consistency and performs well in comparison to similar tests in populations with low formal education levels.9,10

With these results in mind, Dr Farombi asked, “should we continue to use MMSE alone or look at it holistically and combine different cultural biases and environmental and education backgrounds in making a clinical trial design that’s inclusive?”

 

The Montreal Cognitive Assessment

The Montreal Cognitive Assessment (MoCA) is a 10−15 minute screening test that is available in many languages. This 30-point test investigates concentration, orientation, focus and spatial awareness, language and recall, and includes the clock-drawing test. A score ≤25 indicates dementia risk.11,12 The MoCA is used as a secondary endpoint in clinical trials7 but less often in clinical practice11 as it may be more challenging for patients and requires training and certification to use.13

The Montreal Cognitive Assessment is a quick screening test to assess dementia risk

According to Dr Araújo, the MoCA is not only a helpful and relatively comprehensive ‘bedside’ instrument, but also useful for uncovering ‘hidden’ cognitive impairments and for patients with co-pathologies. Advantages to the MoCA include that it is fast to administer and, compared to the MMSE, covers additional cognitive domains and is more sensitive in early-stage AD and MCI. However, it doesn’t assess some cognitive domains relevant to AD, such as apraxia, it can only be administered by a trained healthcare professional, and there are high false positive rates in culturally diverse populations.11,14

 

Digital biomarkers

Digital biomarkers include mobile and wearable devices and applications that can actively and passively collect health data. Such devices can monitor changes in domains that may be relevant to AD progression. As these devices are increasingly being used in the general population, they might prove useful in charting and recognizing cognitive, behavioral, sensory, and motor changes years before otherwise noticeable MCI or mild AD.15

However, highlighted Professor Nilforooshan, a number of issues need to be addressed before digital biomarkers can be widely used. For instance, how accurate and cost-effective devices are, how digital data should be integrated with clinical data, and who should have access to it.16,17

Digital biomarkers may be used in the future to alert to early Alzheimer’s disease-related changes

The ‘Healthy Home’ initiative, being carried out at the Dementia Research Institute at Imperial College London, UK, gives patients simple biometric devices that can measure, for instance, blood pressure, temperature, gait, and walking speed. The devices show changes in an individual’s biometric measures so they can be contacted if something adversely changes. This, said Professor Nilforooshan, means a patient can be seen at a clinic when needed, instead of having to have regular, scheduled check-ups that may be too near or too far apart for each person’s needs.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References
  1. Morris JC. Neurology. 1993; 43: 2412-2414.
  2. Cedarbaum JM, et al. Alzheimers Dement. 2013 ;9(1 Suppl): S45-55.
  3. Tractenberg RE, et al. Alzheimer Dis Assoc Disord. 2001; 15: 155-161.
  4. Dementia Care Central. Mini-Mental State Exam (MMSE) Alzheimer's/Dementia Test: Administration, Accuracy and Scoring. Available at: https://www.dementiacarecentral.com/mini-mental-state-exam/. Published 2020. Accessed: 8 July 2022.
  5. Mitchell AJ. J Psychiatr Res. 2009; 43: 411-431.
  6. Folstein MF, et al. J Psychiatr Res. 1975; 12: 189-198.
  7. Evans S, et al. Eur J Epidemiol. 2018; 33: 635-644.
  8. Benoit JS, et al. Am J Alzheimers Dis Other Demen. 2020; 35: 1533317520918719.
  9. Paddick SM, et al. BMC Geriatr. 2015; 15: 53.
  10. Gray WK, et al. J Geriatr Psychiatry Neurol. 2014; 27: 110-118.
  11. Nasreddine Z. MoCA Cognitive Assessment. Available at: https://www.mocatest.org/faq/. Published 2022. Accessed: 8 July 2022.
  12. Dementia Care Central. Montreal Cognitive Assessment Test (MoCA) for Dementia & Alzheimer's. Available at: https://www.dementiacarecentral.com/montreal-cognitive-assessment-test/. Published 2020. Accessed: 8 July 2022.
  13. Trzepacz PT, et al. BMC Geriatr. 2015; 15: 107.
  14. Thomann AE, et al. J Alzheimers Dis. 2018; 64: 643-655.
  15. Kourtis LC, et al. NPJ Digit Med. 2019;2: doi: 10.1038/s41746-019-0084-2
  16. Bent B, et al. J Clin Transl Sci. 2020; 5: e19.
  17. Ku JP, Sim I. NPJ Digit Med. 2021; 4: 83.
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