Subjective memory complaints, mood and MCI: A follow-up study Jen Yates, Linda Clare, Bob Woods and MRC CFAS Bangor University

Background: Subjective memory complaints (SMC) People report problems with, or changes in, their memory Common in older people Assessments vary from brief questions to in-depth questionnaires such as the Memory Functioning Questionnaire (MFQ; Gilewski et al., 1990) SMC are related to a lower quality of life for older people (Mol et al., 2006; Iliffe & Pealing, 2010) SMC can occur when older people report memory problems or changes in their memory for example: not being able to remember where their glasses are, appointments, or mentioning that their memory is not as good as it used to be. Brief questions: have you noticed any changes in your memory?

Background: Mild cognitive impairment (MCI) A concept developed to describe the transitional phase between normal and pathological ageing Criteria include objective impairment in memory or other cognitive domain, intact general cognitive functioning, intact activities of daily living, absence of dementia, presence of SMC However, there are 19 variations of this criteria so far Only ten versions of the criteria include SMC As many as 62% of individuals who experience cognitive decline do not report SMC (Illife & Pealing, 2010) Think about a continuum between normal ageing and pathological ageing such as dementia – MCI sits in between this A-MCI: memory impairment N-MCI: impairment in another cognitive domain such as language M-MCI: impairments in more than one cognitive domain, memory or otherwise Objective impairment measured through tests of cognitive function and cut off scores are used to determine what constitutes impairment 19 variations differ in the extent to which they endorse the criteria listed above Individuals who experience cognitive decline but do not report SMC are missed from the MCI diagnosis – this lowers the prevalence of MCI and people who have cognitive impairment are likely to miss out on receiving assistance

Background: Mood SMC have been related to depression and anxiety Depression may enhance negative attributions and distort the subjective appraisal of memory Increases in anxiety have been associated with increases in SMC despite no decrease in objective memory performance Symptoms of anxiety and depression are increased in people classified as having MCI Anxiety and depression may indicate a risk factor for the development of MCI, a reaction to the onset of cognitive decline, or both Several ways the relationship between mood and SMC may operate: People with depression may appraise their memory more negatively Depression can cause temporary cognitive disturbances Worried well: anxiety may cause people to worry more about their memory Anxiety may cause people to be more vigilant to changes in their memory Recent systematic review and meta analysis conducted by our team found that anxiety and depression were increased in people with MCI

Research questions: Are people with MCI more likely to have symptoms of anxiety or depression than people with normal cognitive functioning? Are people with SMC more likely to report symptoms of anxiety or depression than people without SMC? Does anxiety or depression at baseline predict the presence of SMC after two years?

Methods: Design Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) Longitudinal population based study involving participants from five areas of England and Wales Participants were initially screened regarding general health and day to day activities A subsample completed a detailed assessment Participants were assessed again after 24 months Baseline and follow-up data is presented in this analysis MRC CFAS conducted in 1990 onwards Over 13000 participants originally screened 2640 selected for detailed assessment which included cognitive measures and measures of mood

Methods: Participants People aged over 65 years and living in Gwynedd, Cambridge, Nottingham, Newcastle and Oxford areas Randomly sampled between 1990 to 1991 Participants were excluded from the analysis at baseline if they had a diagnosis of dementia (n=587), impaired ADLs (n=475) or other cognitive impairment no dementia (OCIND; n=234) 1344 participants at baseline and 896 participants at follow-up Details of participants were obtained from GP records

Methods: Classification of SMC and mood SMC indicated by self report of memory problems by the participant “Have you had any difficulty with your memory?” Anxiety and depression were used to investigate mood Geriatric Mental State Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) A score of two indicated mild symptoms and a score of three indicated a definite case. Participants with scores of two or higher were considered in this analysis SMC was a question in the interview and resulted in a dichotomous category AGECAT is an algorithm which is used to classify symptoms of mood based on the questions asked in the interview.

Methods: Classification of MCI MCI was defined according to Petersen criteria and included the amnestic, non-amnestic and multiple-domain subtypes MCI: objective cognitive impairment, intact ADLs, intact general cognitive function, SMC and no diagnosis of dementia MCIW: participants meet criteria for MCI but do not have SMC OCIND: other cognitive impairment no dementia. Participants have general cognitive decline, intact ADLs and did not meet criteria for dementia ADL: participants with impairments in ADLs and general cognitive decline but did not meet criteria for dementia Dementia was determined by the AGECAT algorithm.

Results: Descriptives 787 (58.6%) of participants had SMC at baseline 49.5% of participants had MCI or MCIW at baseline Table 1: Sample characteristics for participants with and without subjective memory complaints at baseline.   Baseline Follow-up No SMC SMC Total Age mean(sd) 73.69 (6.15) 74.56 (6.50) 1344 (100) 75.41 (6.17) 76.68 (6.62) 896 (100) MMSE mean (sd) 25.13 (3.69) 24.86 (3.49) 25.40 (3.47) 25.07 (3.13) Female N(%) 501 (63.7) 360 (64.6) 433 (65.7) 151 (63.7) Years in FT Education mean (sd) 9.86 (2.13) 10.03 (2.23) 9.98 (2.12) 10.12 (2.32) Without depression (%) 629 (79.9) 370 (66.4) 546 (82.9) 141 (59.5) With depression (%) 158 (20.1) 187 (33.6) 113 (17.1) 96 (40.5) Without anxiety (%) 766 (97.3) 514 (92.3) 651 (98.8) 214 (90.3) With anxiety (%) 21 (2.7) 43 (7.7) 8 (1.2) 23 (9.7) Total (%) 787 (58.6) 557 (41.4) 659 (73.5) 237 (26.5) Level of SMC and cognitive impairment according to our definitions is relatively high Few differences otherwise between people with SMC and without in terms of age, education, mmse. Less people at follow-up for reasons such as elective withdrawal, death and moving out of study area.

Results: Changes in cognitive status over two years Several participants changed cognitive status over the two-year period Change in cognitive status over the two years from baseline to follow-up – perhaps depression is acting as a reaction to worsening cognitive decline, or both part of a similar pathological process

Results: Are people with MCI more likely to have anxiety or depression? The odds of having symptoms of anxiety or depression at baseline were significantly increased in participants classified as MCI The odds of having symptoms of anxiety or depression at baseline were decreased in participants classified as MCIW The odds of having symptoms of depression at follow-up were increased in participants classified as MCI at baseline The odds of having symptoms of depression at follow-up were increased in participants classified as MCI at follow-up Only difference between MCI and MCIW participants is presence of SMC Depression increased at follow-up for those who had MCI at baseline and at follow-up: Note – these are not necessarily the same people as people can change categories in any direction.

Results: Are people with SMC more likely to have anxiety or depression? The odds of having symptoms of anxiety or depression were higher in participants who reported SMC compared to those who did not report SMC at baseline and at follow-up A significant association was found between the presence of anxiety or depression at baseline and the presence of SMC at follow-up The relationship remained significant after anxiety and depression at follow-up were controlled for, with anxiety accounting for 44% and depression accounting for 41% of the variance in SMC at follow-up Having anxiety or depression at baseline might lead to the development of SMC after two-years

Discussion: Main findings Symptoms of anxiety and depression were increased in people with MCI, but decreased in people with MCIW Symptoms of anxiety and depression were increased in people with SMC, and were associated with the presence of SMC after two years Suggests that anxiety and depression may be related to SMC rather than cognitive impairment.

Discussion: Limitations Sample size at follow-up is small and may have impacted on statistical power Progression from one cognitive status to another does not happen in a straightforward manner The presence of SMC in participants is unstable over time Questions used in the interview to assess anxiety and depression may not be sensitive enough to draw out less severe or less frequent instances of symptoms The numbers of people reporting anxiety at baseline with or without SMC were just 8 and 23, so very small. Participants can move from MCI back to no cognitive impairment for example, people don’t progress in a linear fashion which does make seeing changes quite difficult Some participants who have SMC at baseline no longer report it at follow-up We did include AGECAT level 2 to account for milder symptoms

Discussion: Strengths CAMCOG is a well-established screening tool The MCIW category has not been used in previous research to directly compare to participants classified as MCI Large, representative population sample CAMCOG is used in many studies and in clinical practice MCIW category allows a direct comparison between people with SMC and without as the participants are similar in terms of other criteria that they meet. Due to the sampling nature from GP surgery lists and method of approach it ensured the sample was very representative and did not consist of people who had been identified through service/hospital use, as can be common in studies of older people.

Discussion: Implications The MCIW category shows that a large number of people who would otherwise meet criteria for MCI are missed due to not reporting SMC Reporting of SMC could be investigated further by health professionals as it may indicate presence of anxiety or depression in addition to, or instead of, memory problems Future research could be conducted using more frequent time points to detect change in cognitive function and assess the stability of SMC Early intervention in cognitive problems can help to slow down the development of further cognitive decline. People diagnosed as having MCI progress to dementia at a rate of 10-12% annually compared to people with normal cognitive functioning at a rate of 3% annually. SMC may be a marker for other issues, such as anxiety or depression. As such, older people reporting memory problems could be asked about their mood as well as their memory to see if help could be offered. Due to unstable nature of MCI and SMC, more frequent time points could used in future research to see how quickly or how often participants change cognitive status

For further information please email j.yates@bangor.ac.uk Thank you Any questions? For further information please email j.yates@bangor.ac.uk