ASSESSMENT OF COGNITIVE FUNCTION

In Chapter 1 the relationship between OSA and cognitive function was reviewed, with a discussion of the possible mechanisms that may cause cognitive dysfunction in patients with OSA. In Chapter 2, I will review the cognitive tests used in the experimental Chapters 3-5. The tests were selected based on the results of previous studies carried out by the Sleep Group at the Royal Brompton Hospital (Fig

2.4). A further discussion of the changes in brain morphology and function that may lead to the

cognitive impairment is given in Chapter 3, Section 3.2. .

Figure 2.4: This diagram shows the cognitive testing battery examining different aspects of memory

and attention used in the studies of (Twigg et al., 2010). The battery was designed in consultation with Dr Kim Graham, MRC Cognition and Brain Sciences Unit, Cambridge. Each test was selected to examine aspects of long-term memory (semantic and episodic) and working memory. Episodic memory tests was further divided into verbal and visual tests. Two aspects of working memory were included in the battery, specifically maintenance of working memory and dual task performance. Several tests of attention were included in order to cover the different aspects of attention.

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2.4.1 Logical Memory

The Logical Memory test (WMS III, Harcourt, UK) is a validated test of verbal episodic memory. The different components of the test allow assessment of different subsets of episodic memory such as recognition memory, immediate recall and delayed recall. Two short stories are read to the subject. After each story is read the subject is asked to repeat the story, using as close to the same words as he can remember (immediate recall). One point is awarded for each unit of the story correctly repeated according to criteria supplied with the test. The subject is asked to repeat the 2 stories a second time 35 minutes after they were read (delayed recall). The same scoring system is used. Immediately following this second repetition the subject is asked a series of true-false questions about the stories (recognition memory). One mark is scored for each correct answer.

2.4.2 Trail Making

This is one of the most widely used neuropsychological tests and is included in most neuropsychological panels. TMT provides information on visual conceptual and visuo-motor tracking, motor speed, attention and executive functions. It consists of two parts, A and B. TMT – A is a dot-to- dot in which circles containing the numbers 1 to 25 must be joined in numerical order by a line. In TMT – B the circles contain either a number (1 to 12) or a letter (A to L). The aim is to join the circles in numerical and alphabetical order, alternating between letters and numbers (e.g. 1, A, 2, B, 3, C, 4, D etc.). The time taken to complete the tests is measured. Younger subjects and those with more years of education complete the test in less time than older subjects and those with fewer years of education, although normative data is available (Tombaugh, 2004). Most subjects complete the test in less than 300 seconds (Reitan, 1979).

2.4.3 Spatial Span

Spatial Span Forward and Backwards is a discriminator of visual-spatial processing and working memory. The examiner takes a standardised board with 10 cubes in set positions on the board and points to a predetermined series of cubes. The subject is required to repeat the series in the same order (forward span) or in reverse order (backwards span). The sequences gradually increase in length as the test proceeds, from a minimum of 2 cubes, to a maximum of 9 cubes. One point is scored for each correct series, resulting in a maximum score of 16 in both parts of the test. Both tests are validated discriminators of cognitive impairment but spatial span backwards is more sensitive (Wiechmann et al., 2011). Spatial Span forward mainly tests attention. Spatial Span backward tests working memory and executive function as information must be held in the memory and processed.

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2.4.4 Digit Span

Digit Span is similar to spatial span, but instead of a having to repeat a series of tapping cubes, the subject has to repeat a series of digits that are read to him. Again there is a forwards and a backwards component of the test and the series grows in length as the test proceeds. Digit Span forwards mainly tests auditory attention. Digit Span backwards mainly tests working memory and executive function.

2.4.5 ACER

This test (not listed in Fig 2.4) is an assessment of global cognitive function. It has been validated as a discriminant of even mild cognitive dysfunction (Mioshi et al., 2006). It incorporates the Mini Mental State Examination (MMSE), the most widely used screening tool for a global assessment of cognitive function (Folstein et al., 1983), but also encompasses cognitive domains not assessed in the MMSE including attention, orientation, memory, verbal fluency, language and visuospatial skills.

The test comprises a series of questions and simple tasks such as memorising an address, obeying a 3 stage command and drawing a clock face. ACE-R is available and has been validated in many languages (including English, Japanese, Cantonese, Italian and Slovak. It takes approximately 15 minutes to complete the test. There are 26 tasks in total with a maximum possible score of 100, with individual scores for each domain. There are age and education dependent norms for the total score as well as for the individual domains. A cut-off score of 88 is 94% sensitive and 89% specific for the diagnosis of dementia. A cut-off of 82 is 84% sensitive and 100% specific.