Measuring cognitive function

Psychological tests are used to measure individual differences related to a psychological concept such as a cognitive domain, based on a sample of relevant

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behaviour in a scientifically controlled situation (117). They can be used, in a general sense, to assess cognitive capabilities of humans (e.g. intelligence tests) or to assess more specific cognitive functions which are known to be related to a specific brain structure or pathway (e.g. neuropsychological tests). Further, structured cognitive assessment measures can be accurate and valuable in the early detection of dementia or MCI (118) which can make a difference to the treatment and prognosis for the individual.

A plethora of cognitive tools are available to measure cognitive function. This can make the interpretation (and comparison) of studies investigating cognitive function difficult given the complexity of cognition itself, as well as inconsistencies in the cognitive tasks used across studies and the way that cognitive test data are analysed and reported (119). It is therefore important to select appropriate tools which are sensitive and specific with regard to what is being measured and for the population being assessed. Table 2.1 provides an overview of commonly used cognitive tools which have been found to be sensitive to cognitive change in trials assessing the effects of nutrition.

Table 2.1. Commonly used cognitive tools which have been shown to be sensitive to change in response to a dietary intervention

Tests Advantages Limitations

7-Minute Screener - Little or no education bias - Validated in primary care - Difficult administration - Complex scoring Abbreviated mental test (AMT)

- Easy administration - Verbal memory test

- Education/culture bias - Does not test executive

function of visuospatial ability Cambridge Cognitive Examination (CAMCOG)

- Tests many domains - Difficult and long administration

- Lacks standardisation for scoring and administration General

practitioner assessment of cognition (GPCOG)

- Developed for and validated in primary care

- Informant component useful when initial complaint is informant- based - Little or no education bias - Based on informant responses

- Lacks data on any language/culture biases

19 Mini-Cog - Developed for and

validated in primary care

- No culture/education bias

- Use of different word lists may affect failure rates

Memory

impairment screen (MIS)

- Verbal test (no writing/drawing) - Little or no education

bias

- Does not test executive function or visuospatial skills Short Portable Mental Status Questionnaire (SPMSQ)

- Verbal test (no writing/drawing)

- Scoring can be cumbersome

- Does not test short-term memory Short Test of Mental Status (STMS) - Validated in primary care

- Tests many separate domains

- Education/culture bias - Studied in well-educated

subjects Stroop test - Multiple variants

- Quick administration - Easy scoring

- Some education bias

Time and Change Test (T&C) - Very brief administration time - Little or no education bias - Strong language/cultural bias

Mini Mental State Exam (MMSE)

- Most widely used - Brief administration

- Education/age/language/c ulture bias

- Ceiling effect (highly educated impaired subjects pass)

- Best performance for at least moderate cognitive impairment

Behaviour rating inventory for executive function (BRIEF-A)

- Parent and teacher forms - Inexpensive - Comprehensive coverage of subdomains of executive functioning - Used extensively in

research with good sensitivity

- Easy to administer and complete

- Parent rating are susceptible to bias - Report of everyday

executive function does not necessarily accurately parse subdomains of executive function

Clock drawing test (CDT)

- Very brief

administration time - Minimal education bias

- Lacks standards for

administration and scoring CogState - Developed for repeat

testing

- Minimal practice effects

- Practice effects have been observed in healthy controls during repeat assessments in a single

20 - Discriminant ability to

differentiate patients with MCI or AD from healthy controls comparable to standard neuropsychological tests day Rowland universal dementia assessment (RUDAS) - Designed for multicultural populations - Little or no education/language bias - Validated in Australian community

- Limited use due to recent development

Short and Sweet screening

instrument (SAS- SI)

- Detects dementia better than

neuropsychological testing in community population

- Does not test memory - Lacks data on any

education/language/cultur e

- biases Short Blessed Test

(SBT)

- Verbal test (no writing/drawing)

- Education/language/cultur al/ race bias

- Scoring can be cumbersome

- Does not test executive function

St Louis

University Mental Status (SLUMS)

- No education bias - Tests many separate

domains

- Limited use due to recent development

Trail making - Quick administration - Easy scoring

- Possible practice effects - Part B more sensitive Montreal

Cognitive Assessment (MoCA)

- Designed to test for mild cognitive impairment

- Tests many separate domains

- Lacks studies in general practice settings - Education bias

- Limited use due to recent development CANTAB Stockings of Cambridge - Computer administration - Non-verbal administration

- May lack the sensitivity to measure discrete cognitive functions in healthy populations Digit span (forward and backward)

- Reliable and valid - Lack of standardised procedure

Weschler Adult Intelligence Scale- Revised (WAIS-R)

- Reliable - Relatively weak

assessment of processing speed and working memory

- Commonly administered by psychologists

21 Rey Auditory-

Verbal Learning Test (RAVLT)

- Easy administration - Potential education bias

Rey-Osterrieth Complex Figure Copy - Standardises a common stimulus - Reliable discriminating power - Diagnostically powerful - Identifies possible causes of memory deficits - Scoring system is complex and prone to error

Adapted from Best et al. (2015), Pase et al. (2014) and Cordell et al. (2013) (118-120).

An important consideration in cognitive testing is choosing a measure which can detect cognitive impairment and which is sensitive to subtle changes in cognitive function. This is generally done by comparing a test score to normative data. However, many cognitive measures do not provide normative data which is divided into age groups and this can become problematic, particularly when assessing cognitive function in older adults who are more at risk of cognitive decline (120). Further, some of the most commonly used outcome measures in clinical trials listed in table 2.1 such as the MMSE and MoCA, are often used as screening tools in a clinical setting (120). While these tests are effective in detecting severe and pathological impairment, they have been found to be unreliable in detecting MCI (120). This can become problematic when testing healthy older adults. While there is no ‘gold standard’ tool for detecting cognitive impairment, guidelines developed by a workgroup of professionals from the United States of America (USA) with expertise in detecting cognitive impairment, suggest that a specific cognitive evaluation is required, preferably with a baseline measure, and the inclusion of memory and language in the assessment, can enhance detection of impairment (118).

Another limitation is that many of these commonly used cognitive tools are only available in hard-copy form which increases the risk for loss of data and researcher error when entering/scoring data. More recently, the introduction of computerised cognitive testing has overcome some of these limitations through the customisation of testing batteries, ease of transport and administration and reduction of researcher error as data is automatically recorded. One commonly used computerised test is CogState. The CogState Brief Battery computerized test (http://cogstate.com/) is a multi-faceted program which assesses a variety of cognitive functions including

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attention, processing speed, memory and executive function. It provides written instructions on a computer screen prior to stimuli being displayed in the form of playing cards, a maze or other stimuli depending on the tests selected. Responses are given by the participant using minimal keyboard keys or the mouse. The advantages of this tool include its versatility in testing a range of cognitive domains through the creation of customised batteries and composite scores, as well as its sensitivity for use in an older population. CogState has been found to be sensitive to cognitive decline in healthy adults as well as adults with MCI (121) and has been validated for repeated administration over multiple time points with minimal practice or fatigue effects even over a short time period, thus making it a suitable test to detect subtle changes (122, 123). It has also been found to be suitable for use in an older population with little computer experience and requires limited supervision (124). In comparison to the MMSE, it has higher discriminant ability for differentiating between healthy individuals and those with MCI (124).

Although there is evidence to suggest that some cognitive tests may be more suitable/ reliable or sensitive to cognitive change, it is important to note that all cognitive testing is subject to the influence of environmental factors such as the time of cognitive testing, room temperature, previous night’s sleep quality and fasting state of the participants (125, 126). Thus, it is important to attempt to control and standardise these factors when doing repeated cognitive testing in participants, and to consider the potential impact of these factors when interpreting the findings of cognitive studies.

In summary, there is a wide range of cognitive tools which can be used to measure cognitive function. This has led to a lack of consistency between studies making the results of cognitive trials difficult to interpret and compare. The limitations of traditional pen and paper questionnaires have given rise to the increasing use of computerised cognitive testing including CogState. Previous evidence supports the use of CogState in healthy older adults for detecting subtle non-pathological cognitive change therefore CogState was selected as an outcome measure for this thesis.

23 1.2 Cognitive Impairment

Ageing can affect cognitive abilities at different rates with varying severity and it has become apparent that the changes that occur due to the chronological age of the brain are not always consistent with the biological age of the brain (88). For most populations, there is a premorbid range within which individuals are expected to function in terms of their cognitive ability. If performance is sub-standard, this may be indicative of cognitive impairment or decline (127). Cognitive impairment can be best thought of as a continuum and as illustrated in Figure 2.3, there is a marked difference between the gradual decline that comes with ageing compared to pathological impairment (12).

Figure 2.3: Progression from normal ageing to AD or another dementia (12).

As mentioned above, changes in cognitive function can be assessed across multiple domains (128). Age-related declines are generally gradual and minor such as forgetting a relative’s birthday (12), whereas pathological declines can be quite rapid and severe such as forgetting family members. Those which exceed the expected decline rate may be classified as having pathology which is often termed MCI or ‘cognitive decline without dementia’ (128). MCI is defined as a stage between normal cognitive decline and dementia where memory loss is greater than expected but does not display other signs of dementia (129). There are four main types of MCI which include amnestic, non-amnestic, single domain and multiple domain (12). Amnestic impairs memory while non-amnestic spares memory but impairs other cognitive abilities such as executive function (12). Single domain MCI, as the name

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suggests, only affects one cognitive domain while multiple domain MCI impairs abilities across multiple domains (12). It is generally accepted that MCI is a precursor for dementia and it is currently estimated that individuals with MCI have a three to five times higher risk of developing dementia compared to others of similar age (130). Indeed, current data suggests that 10% to 15% of individuals with amnestic MCI progress to AD each year, which is substantially higher than the general population incidence rates of AD of 1% to 2% each year (129).

Dementia is defined by the World Health Organisation (WHO) as a gradual decline in cognitive, social and physical functioning due to brain disease or damage not attributed to the normal process of ageing (11). It is an umbrella term which is associated with over 100 different diseases (2). Common symptoms associated with dementia include memory loss, impairment of perception, language and personality and severe cognitive decline (2, 131).

There are many types of dementia and each type has different risk factors and progression of symptoms. The most common types of dementia are AD, vascular dementia, frontotemporal dementia and dementia with Lewy bodies (2). However, it is common for these types of dementia to co-exist and so the distinction between symptoms and diagnosis of a particular type of dementia becomes difficult (2). Throughout this thesis the term dementia will be used in a general sense to refer to all types of dementia including comorbidities (of different types of dementia), unless otherwise specified.