IPA Bulletin
Recent Advances

William Burke ● United States
Wendy Moyle ● Australia
Mark Rapoport ● Canada

Special Announcement
It is with pleasure that we introduce our new editors of the Research and Practice section and authors of the “Recent Advances” column.

William Burke
William J. Burke, M.D. is the Anna O. Stake Professor and Vice-Chair for Research in the Department of Psychiatry at the University of Nebraska Medical Center in Omaha, Nebraska – United States. He also is the Director of the Psychopharmacology Research Consortium at UNMC. Dr. Burke has extensive experience in clinical trials and his research interests include evaluation of potential new treatments for Alzheimer disease, and depression. His current NIH-funded research is testing whether depression can be prevented in patients being treated for cancer of the head and neck.

Wendy Moyle
Professor Wendy Moyle is Professor of Nursing and Deputy Director for the Research Centre for Clinical and Community Practice Innovation at Griffith University in Brisbane, Australia. Professor Moyle coordinates research higher degree students and gerontological nursing and chairs the University Human Research Ethics Committee. Her research involves older people, people with dementia and nursing education. Her current projects include an exploration of moral worth and QOL in people with dementia, sleep and activity in people with dementia and their carers and loneliness in older people.

Mark Rapoport
Mark Rapoport, MD is Associate Scientist, Clinical Integrative Biology – Brain Sciences Program at the Sunnybrook Research Institute, Staff Psychiatrist at the Sunnybrook Health Sciences Centre and Associate Professor, Department of Psychiatry, Division of Geriatric Psychiatry at the University of Toronto, in Toronoto, Ontario – Canada. Dr. Rapoport is also a member of the Canadian Driving Research Initiative for Vehicular Safety in the Elderly (CanDRIVE), and an associate editor of the Canadian Journal of Geriatrics. Dr. Rapoport’s research focuses on neuropsychiatric sequelae of traumatic brain injury in the elderly, pharmacoepidemiology, and predictors of motor vehicle collisions in the elderly.

Can Alzheimer's disease be Prevented?

Alzheimer's disease is often considered a disease of old age. However, recent amyloid imaging studies suggest that the actual onset of the disorder may occur much earlier, years or even decades, before the disease declares itself. This has led to an increased emphasis on early detection, and in particular, on prevention of the illness.

In April 2010, the National Institutes of Health (NIH) sponsored a two and a half day summit held in Washington, DC, United States. The purpose of this conference was to summarize all available evidence regarding whether Alzheimer's disease and cognitive decline can be prevented. During the conference, experts summarized evidence on a number of key questions and have now published a draft consensus statement (http://consensus.nih.gov/2010/alz.htm). All presentations from the conference are freely available at the same site via webcast.

The overarching question was: What factors are associated with a reduction of risk for Alzheimer's disease? Importantly, a wide variety of possible preventive factors were considered, including: nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins, and environmental exposures. The bottom line was that “there is currently no evidence considered to be of even moderate scientific quality supporting the association of any modifiable factor with reduced risk of Alzheimer's disease.”

Some factors that had weak evidence to support a role in prevention were recognized. These included adequate levels of folic acid, adherence to a diet low in saturated fats and high in fruits and vegetables, use of statins, light to moderate use of alcohol, more years of education, higher levels of cognitive engagement, and participation in physical activities. All of these factors have been reported to be associated with reduced risk of Alzheimer's disease. Certain compounds were singled out for which there is NO consistent evidence to suggest any role in prevention, including: ginkgo biloba, beta-carotene, flavinoids, multivitamins, and vitamins B12, C, and E.

Throughout this review, the authors repeatedly emphasized that there is often very little data on which to base conclusions and that the quality of the evidence is typically low. A key reason for this dearth of evidence is that obtaining Level I evidence from a placebo-controlled, AD prevention trial is a very expensive endeavor that can take 5-10+ years to complete. The final recommendation of the report was that there is an urgent need for conducting rigorous, state-of-the-art, methodologically sound research to address these deficiencies.

Jessen F et al: Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment. Arch Gen Psychiatry. 2010 Apr;67(4):414-22. A group of researchers in Germany report on the implications of subjective memory impairment in 2415 subjects, 75 years or older, without cognitive impairment who participated in the German Study on Aging, Cognition and Dementia in Primary Care. These patients were examined at baseline and followed up 1.5 and 3 years later. The investigators were interested in whether subjective memory impairment (SMI) might precede both mild cognitive impairment (MCI) and dementia. In addition, they examined whether subjective worry about memory loss might be predictive of dementia. All subjects were asked at baseline: “Do you feel like your memory is becoming worse?” and possible answers were “no,” “yes, but this does not worry me,” or “yes, this worries me.” Subjects with SMI with worry (P<.001) and without worry (P<.02) at baseline had an increased risk for dementia at follow-up 1 or 2. Even higher risks of developing dementia were seen in the group who had SMI at baseline and converted to MCI at follow-up 1 (OR 8.92 for any dementia, 19.33 for dementia in AD). The group that had MCI at baseline and amnestic MCI at the first follow-up had the highest risk of developing dementia at follow-up 2 (OR 29.24 for any dementia, 60.28 for dementia in AD) with a sensitivity of 66% and specificity of 98.3% for conversion to dementia in AD. These data provide additional support for the notion that SMI may be the earliest clinical manifestation of AD and that worry accompanying SMI may identify a group at even higher risk.

Alternative Pathways to Better Care for Older People: Nursing Research Involving Complementary and Alternative Medicine

The number of people using Complementary and Alternative Medicine (CAM) is rapidly rising among health care consumers internationally. Alongside this growth in CAM use have been concerns about the safety and efficacy of CAM and the need to regulate CAM practitioners. The latest issue of the Journal of Clinical Nursing (Volume 19, 2010) is devoted to research involving CAM, and several of these papers relate to older people and include CAM use in older people with dementia, anxiety or depression.

Three of the studies reported below were undertaken in Taiwan where traditional Chinese medicine has been the main medical treatment since the Ming and Ching Dynasties (AD 1368-1911).

Music
Sung, HC, Chang AM & Lee WL. (2010) A preferred music listening intervention to reduce anxiety in older adults with dementia in nursing homes. Journal of Clinical Nursing, 19, 1056-1064.

A quasi-experimental pre-test and post-test design was used to evaluate the effectiveness of a preferred music listening intervention on anxiety in older people with dementia living in long-term care in Taiwan. The intervention group (n=29) were treated with 30-minutes of a music listening intervention based on personal preferences, twice a week for six weeks. The control group (n=23) received standard care with no music. Anxiety was measured by the Rating Anxiety in Dementia (RAID) scale. Participants who received the intervention had a significantly lower anxiety score at six weeks compared to the control group (F=12.5, p=0.001). The authors argue that the importance of music in the life of participants was positively related to a reduction in anxiety.

Chang FY, Huang HC, Lin KC & Lin LC. (2010). The effect of a music program during lunchtime on the problem behaviour of the older residents with dementia at an institution in Taiwan. Journal of Clinical Nursing, 19, 939-948.

This study used a quasi-experimental design with an eight-week time series follow-up. A total of 41 older residents with a diagnosis of dementia were involved in a music intervention while dining on their lunchtime meal. The music chosen for the intervention was nature music with a tempo that mimics the human heart beat (60-80 beats per minute). The Chinese Version of the Cohen Mansfield Agitation Inventory (C-CMAI) community form was used as the outcome measure. The findings show the intervention reduced, significantly, physical and verbal aggression on the C-CMAI score. The findings suggest there was a one-week time lag between implementation of the intervention and a significant effect on participants’ behaviours.

As a comparison to the above two studies here is another study that found different results for music participation:

Cooke M. Moyle W. Shum D. Harrison S. & Murfield J. (In press). A randomised control trial exploring the effect of music on agitated behaviours and anxiety in older people with dementia. Aging and Mental Health.

This study used a randomised cross-over design to explore the effect 40 minutes of live music participation, three times a week, for eight weeks, had on agitation and anxiety in older people with dementia (n=47) living in long-term care. The control group involved an active reading group that mirrored the music intervention timelines. The findings identified that attendance in a live music group three times a week did not significantly affect agitation and anxiety in older people with dementia. Participants were assessed three times on the Cohen-Mansfield Agitation Inventory Short Form (CMAI-SF) and Rating Anxiety in Dementia Scale (RAID). A sub-analyses of 24 participants attending >50% of music sessions found a significant increase in the frequency of verbal aggression overtime, regardless of group (F (2,46) =3.3534, p<0.05). A series of multiple regressions found cognitive impairment, length of time living in the facility, and gender, to be predictors of agitation overall and by subtype. Both music and reading groups enabled participants a ‘voice’ and increased their verbal behaviour.

Attitudes toward CAM
Hsu MC, Moyle W. Creedy D. Venturato L. Ouyang WC. & Sun GC. (2010). Attitudes toward and education about complementary and alternative medicine among adult patients with depression in Taiwan. Journal of Clinical Nursing, 19, 988-997.

This paper reports on an investigation of patients’ attitudes toward CAM and education provided by nursing staff about CAM, and tests whether education mediates the effect of CAM use and attitudes toward CAM. A face-to-face survey was conducted with 206 older people hospitalised in Taiwan for treatment of depression. Instruments included The Attitudes towards CAM Questionnaire and The Patient Education about CAM Questionnaire. Two-thirds of participants (66.5%) reported they had inadequate knowledge of CAM. Slightly more than one-third of participants (40.3%) were unsure if CAM use was contraindicated when taken with antidepressants. Participants reported that taking CAM was better than not taking anything for depression. Slightly more than half (55.8%) of the participants had not disclosed their CAM use to their nurse or psychiatrist. In addition, participants reported they did not know whether their psychiatrist was opposed to their use of CAM. Two-thirds of participants (66%) reported their nurse did not ask about CAM use during routine assessments or conversations. The authors discuss the potential for adverse drug interactions, such as those observed with Ginseng and St. John’s Wort, and the importance of identifying whether patients are taking CAM. They also argue the need for nurses to ask questions about CAM use and to provide education on CAM and the potential interactions with antidepressants.

Other aspects of this study have been reported in the following journals:
Hsu, M., Moyle, W. Creedy, D. Venturato, L. Ouyang, WC & Tsay, SL. (2009) Use of antidepressants and complementary and alternative medicine among outpatients with depression in Taiwan. Archives of Psychiatric Nursing, 23 (1), 75-85.

Hsu, M. Creedy, D. Moyle, W. Venturato, L. Tsay, SL. & Ouyang, WC. (2008). Use of complementary and alternative medicine among adult patients for depression in Taiwan Journal of Affective Disorders, 111, 360-365.

Recent Studies of Cognition in Brain Imaging, Dementia, and Stroke

Cognition and Brain Imaging
Literature on the neuroimaging of cognition is evolving rapidly. Two recent publications shed light on new approaches to this complex topic. The first is an American multi-centre dataset that will form the basis for neuroimaging studies of the spectrum from healthy aging to Alzheimer’s disease, and the second publication demonstrates the sensitivity of diffusion tensor imaging (DTI) in assessing normal cognitive changes with age.

Petersen et al, Alzheimer’s disease neuroimaging initiative. Neurology 2010; 74: 201-209. A group of researchers from centres across North America have developed a consortium with a goal of developing uniform standards for imaging and biomarker procedures in investigations of patients with MCI, AD and healthy elderly controls. They published a paper describing the clinical characteristics of 229 controls, 192 with AD and 398 with MCI who were evaluated over 36 months. This paper confirms the cross-sectional and longitudinal differences in ADAS-Cog found in other publications, but also demonstrates that CSF measures of beta amyloid-42 were different between the groups and predicted change in cognition. Interestingly, 44% of the subjects with MCI were on cholinesterase inhibitors, and 11% on memantine, neither of which have been approved for this indication. The participants described in this paper for this initiative will form the basis of future studies of cognition, imaging and biomarkers.

Carlesimo et al, Hippocampal mean diffusivity and memory in healthy elderly individuals, a cross-sectional study. Neurology 2010; 74: 194-200. This cross-sectional investigation used diffusion tensor imaging in 76 healthy adults of a wide age span to predict verbal and visual memory. They found that mean diffusivity, a measure of water motion used to investigate pathological brain changes, was associated with verbal and visual memory but brain volume on MRI was not. The study provides an important new imaging paradigm in assessing cognition in healthy elderly that needs to be confirmed with longitudinal analysis.

Cognitive Testing to Distinguish Dementia Types
Before proceeding to neuroimaging, experienced clinicians know that the bedside cognitive examination offers useful tools to distinguish subtypes of dementia, and a recent publication suggests bedside cognitive hints to the presence of Lewy body Dementia.

Palmqvist, S. et al, Practical suggestions on how to differentiate dementia with Lewy bodies from Alzheimer’s disease with common cognitive tests. International Journal of Geriatric Psychiaty 2009; 24: 1405-1412. This group of researchers from Sweden compared 33 patients with Lewy body dementia (DLB) to 66 patients with Alzheimer’s disease matched by gender, age and MMSE, and attempted to characterize the cognitive profiles that distinguish the groups using aspects of the MMSE, as well as the cube-copying task and the clock-drawing test. The authors found that when two of the following three criteria were met, there was an 85% sensitivity and 75% specificity for DLB: 1) Impaired clock drawing test; 2) a non-3D cube copied; and 3) Orientation on MMSE x 3 greater than or equal to total MMSE score. The authors suggest that the presence of 2 or more of these criteria should lead to a more thorough investigation for the diagnosis of DLB.

Cognition and Stroke
Efforts are being made to remediate cognitive dysfunction post-stroke, and cognitive dysfunction itself may be an independent risk factor for stroke. A recent study from Iowa (United States) reported on improvement of memory associated with escitalopram treatment after stroke, and a study from Sweden highlights an independent association between Trails B performance and stroke risk.

Jorge et al. Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry 2010; 67(2) 187-196. A 12-week randomized controlled trial was conducted in Iowa with 129 patients seen within 3 months of acute stroke, in which participants were randomized to escitalopram or placebo and compared to a non-blinded arm of problem-solving therapy for one year. The average age of the participants was in the 60s, but age ranged from 51-89. In the escitalopram group those 65 and over were prescribed 5mg, but the dose was 10mg in the younger group. The authors found a significant improvement in immediate and delayed memory in the subjects in the escitalopram group compared to the other groups, but interestingly found no differences in other neuropsychological tests of attention or frontal-executive functioning. Side effects did not differ between the groups. The groups were well-matched, except for the fact that the escitalopram group was somewhat younger. However, the between-group memory differences remained after they adjusted for confounds including age. The authors discuss the serotonergic modulation of cholinergic transmission in the forebrain as a potential mechanism. Caution must be given to interpretation of the results as the participants assigned to problem solving therapy were somewhat older than the other groups, and the between-group differences in memory scores were somewhat modest.

Wiberg, R. et al Cognitive function and risk of stroke in elderly men. Neurology 2010; 75:379-85. A group of 930 men in Sweden tested with the MMSE and Trails tests were followed for up to 13 years starting at age 70. After adjusting for confounds including cardiovascular risk factors, researchers found that an increase of 1 standard deviation in time to complete Trails B was associated with almost a 50% increase in risk of brain infarction. The study carefully excluded those with strokes at baseline, and only 2% of subjects had an MMSE score at baseline of 24 or less. The authors speculate that the Trails test performance in these subjects may indicate unrecognized cerebrovascular disease.


Reprinted from IPA Bulletin, Volume 27, Number 2