An evidence-based caregiver intervention: Translation from research to practice

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Featured Research Sessions F3-01 Psychosocial Interventions for Individuals with Dementia and Their Caregivers

corticobasal degeneration and other diseases. Tau mutations cause familial forms of frontotemporal dementia, establishing that tau protein dysfunction is sufficient to cause neurodegeneration and dementia. Thus, transgenic mice expressing mutant (e.g. P301S) human tau in nerve cells exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments made of hyperphosphorylated tau protein. In contrast, mouse lines expressing single isoforms of wild-type human tau do not produce tau filaments or display neurodegeneration. Methods: Here we have used tau-expressing lines to investigate whether experimental tauopathy can be transmitted. Results: We show that the injection of brain extract from mutant P301S tau-expressing mice into the brain of transgenic wild-type tau-expressing animals induces the assembly of wild-type human tau into filaments and the spreading of pathology from the site of injection to neighbouring brain regions. The study will be complemented by the intracerebral injection of human tissues from various tauopathies into the brain of both transgenic wild-type tau-expressing mice and wild-type B6 mice. S3-03-06

TAU PATHOLOGY IN YOUNG PEOPLE AND ITS PROGRESSION BEFORE ABETA DEPOSITION

Dietmar Thal1, Ajeet Rijal Upadhaya1, Marcus F€andrich2, Kelly Del Tredici1, Heiko Braak1, 1University of Ulm, Ulm, Germany; 2Max Planck Research Unit for Enzymology of Protein Folding, Halle, Germany. Background: Alzheimer’s disease (AD) is characterized histopathologically by the generation of neurofibrillary tangles (NFTs) consisting of abnormal phosphorylated tau-protein and by the deposition of the amyloid ß-protein (Aß) in senile plaques (SP) and in blood vessels, i.e., cerebral amyloid angiopathy (CAA). Methods: Human autopsy cases from aged individuals with and without dementia were studied. To detect NFTs and SPs immunohistochemistry with antibodies directed against abnormal tauprotein (AT8) and Aß (4G8) was performed. The distribution of NFT pathology (NFT stage) was determined according to Braak and Braak 1991 (Acta Neuropathol., 82; 239-259), that of SP distribution (Aß phase) according to Thal et al. 2002 (Neurology, 58; 1791-1800). To detect soluble Aß-aggregates soluble fractions of brain lysates were analyzed with BN-PAGE, SDS-PAGE, and immunoprecipitation with subsequent western blot analysis. Results: In the human brain, the first AT8-immunoreactive pretangles occur in the locus coeruleus in very young individuals (Braak & Del Tredici, 2011, Acta Neuropathol. 121;171-181), then in the upper raphe nuclei and the transentorhinal cortex (allocortex), whereas Aß-deposits are first seen in the neocortex. In most cases, NFT-pathology precedes Aß-deposition. Both Aß-deposition and NFT-pathology progress in hierarchical sequences into further brain regions as described by the NFT stages and the Aß phases. Although the anatomical progression pathways differ, the time course of both pathologies correlates with one another as well as with the degree of dementia. Soluble Aß-oligomers, protofibrils, and fibrils have been discussed as being causative for the disease. Upon comparing AD cases with non-demented cases with and without Aß-pathology, more high-molecular weight Aß-aggregates were found in the native soluble fraction of AD cases than in that of non-demented cases with Aß-plaque pathology. Using immunoprecipitation, higher levels of SDS-denaturable Aß-oligomers, protofibrils, and fibrils were observed in AD cases than in non-demented individuals. In cases without Aß-plaques that exhibited initial tau pathology (NFT stages I or II) we did not detect measurable levels of Aß-aggregates. Conclusions: Thus, initial Aß pathology as well as initial tau pathology may develop independently of one another. One can speculate that high levels of soluble high-molecular weight oligomers may exacerbate pre-existing tau pathology by allowing it to cross the threshold for developing AD. TUESDAY, JULY 19, 2011 FEATURED RESEARCH SESSIONS F3-01 PSYCHOSOCIAL INTERVENTIONS FOR INDIVIDUALS WITH DEMENTIA AND THEIR CAREGIVERS Chairs: Simon Forstmeier, University of Zurich, Zurich, Switzerland May Mittelman, NYU Langone Medical Center, New York, N.Y., United States

F3-01-01

COGNITIVE-BEHAVIORAL TREATMENT FOR MILD ALZHEIMER’S PATIENTS AND THEIR CAREGIVERS (CBTAC): A CASE STUDY OF A COMPREHENSIVE TREATMENT APPROACH

Simon Forstmeier, University of Zurich, Zurich, Switzerland. Background: About 90% of all mild Alzheimer’s dementia (AD) cases experience neuropsychiatric symptoms, most frequently depression, anxiety, and irritability. Although some research has supported the effectiveness of specific psychotherapeutic approaches for mild AD, there are only few attempts to evaluate a comprehensive, CBT-based, multi-component treatment programme. The CBTAC study is a randomized controlled trial (RCT) that evaluates the effect of such a psychotherapy programme on the health of patients with mild AD and their caregivers. Methods: Participants are recruited via geriatric and memory clinics and general practitioners. The patients and their caregiver will be randomized to either the CBT-based intervention or to the control condition that receives treatment as usual (TAU). The CBT-based programme consists of 20 weekly sessions, including eight modules: diagnosis and goal setting; psychoeducation; engagement in pleasant activities; cognitive restructuring; live review; behavior management; interventions for the caregiver; and couples counselling. TAU is defined as receiving at least three out of six interventions: psychoeducation; appropriate medical treatment; social counselling; memory training; patients’ self-help group; caregivers’self-help group. Before and after the treatment phase, participants in both conditions will be assessed. Follow-ups will take place at 3, 6, and 12 months post-treatment. A single case study will be presented to illustrate the comprehensive treatment approach. A multiple-baseline design was applied. Primary outcome measure is depression, assessed by the Geriatric Depression Scale and the Cornell Scale for Depression in Dementia. Further instruments assess other neuropsychiatric, functional and cognitive symptoms as well as coping strategies of the patients, and depression, anxiety, anger, general health and coping of the caregiver. Results: Data collection is currently under way. The results of the single case study to provide evidence of benefit of the psychotherapeutic intervention will be presented. Additionally, preliminary results of group level analyses will be presented. Conclusions: Findings will be discussed with respect to their conceptual, empirical, and clinical implications. There is an urgent need to establish a comprehensive psychotherapy treatment programme that does not only focus on a single strategy, but incorporates a multi-component treatment programme. If emotional health of cognitive impaired individuals could be effectively treated, the health care costs could be reduced significantly.

F3-01-02

AN EVIDENCE-BASED CAREGIVER INTERVENTION: TRANSLATION FROM RESEARCH TO PRACTICE

Mary Mittelman, NYU Langone Medical Center, New York, N.Y., United States. Background: The NYU Caregiver Intervention (NYUCI) is a multi-component individualized Intervention for spouse caregivers of people with Alzheimer’s disease. The underlying premise of the intervention is that improving social support can have significant positive impact on the well-being of the caregiver. The intervention includes individual counselling for the primary caregiver and family counselling for the spouse and other family members within a fixed period of time and ongoing support as requested for the entire course of the illness. Methods: The NYUCI was evaluated in a randomized controlled trial that lasted more than 2 decades and included 406 caregivers. A comprehensive assessment of the caregivers was completed at intake into the study and repeated every four months for the first year and every six months thereafter, for 2 years after the death of the person with dementia. The assessment included measures of depression, reaction to patient behavior, physical health and social support. Results: The RCT demonstrated that the NYUCI reduced depressive symptoms and reaction to patient behavior and improved physical health for spouse caregivers, enabling them to postpone or avoid nursing home placement by an average of 557 days, or more than

Featured Research Sessions F3-01 Psychosocial Interventions for Individuals with Dementia and Their Caregivers 1.5 years, compared to the usual care control group. The effects continued through the major transitions of nursing home placement and death of the person with dementia. The success of the original study has led to numerous community implementations in the United States. In Minnesota, a Administration on Aging demonstration project is now being embedded in the social service system for the entire state. The results in the first 2 years mirror those obtained in the treatment group in the original study. Conclusions: Our results suggest that a short course of intensive counselling and readily available supportive maintenance that includes not only the spouse caregiver, but also other family members, can have long-lasting effects on the well-being of spouse caregivers. The structure of the NYUCI permits flexibility of content, making it an ideal intervention for diverse cultures. The results of the community implementation efforts will have important implications for future research and for targeting services to assist family caregivers.

F3-01-03

GOAL-ORIENTED COGNITIVE REHABILITATION OF MEMORY IN EARLY-STAGE ALZHEIMER’S DISEASE: SINGLE-BLIND RANDOMIZED CONTROLLED TRIAL OF CLINICAL EFFICACY

of life and mood. The occupational therapy intervention was also (costeffective. Nevertheless, the intervention did not implement itself. Major barriers and challenges were occupational therapists feeling incompetent in treating patients according to the guideline and professionals not referring patients because not being familiar with occupational therapy. Conclusions: We conclude that this community based occupational therapy intervention improved the daily functioning despite the patients’ limited learning ability and caregivers’ quality of life despite the burden of care. A major strength of community occupational therapy is the person centered approach in deriving occupational therapy goals and in reaching these goals. It is also a major challenge to prioritize goals and to harmonize patient and caregiver goals. Special training of occupational therapists is needed to implement the guideline and awareness should be raised in professionals on the potential benefits of occupational therapy. Discussion in this presentation will be focused on nationwide implementation and translation to other settings/ countries of this and other successful psychosocial interventions.

F3-01-05

Linda Claire, Bangor University, Bangor, United Kingdom. Background: This single-blind randomized controlled trial aimed to provide evidence regarding the clinical efficacy of cognitive rehabilitation (CR) in early-stage Alzheimer’s disease (AD). Methods: Participants were 69 individuals (41 female, 28 male; mean age 77.78, sd 6.32, range 56-89) with a diagnosis of AD or mixed AD and vascular dementia and an MMSE score of 18 or above, and receiving a stable dose of acetylcholinesterase-inhibiting medication. Forty-four family carers also contributed. Participants were randomized to either CR, relaxation therapy (RT) or no treatment (NT). The CR group received 8 weekly individual home-based sessions of CR incorporating work on personally-relevant goals supported by components addressing practical aids and strategies, techniques for learning new information, practice in maintaining attention and concentration, and techniques for stress management. The primary outcomes were goal performance and satisfaction, assessed using the Canadian Occupational Performance Measure. Questionnaires assessing mood, quality of life and carer strain, and a brief neuropsychological test battery, were also administered. A subset of participants underwent functional magnetic resonance imaging (fMRI). Results: CR produced significant improvement in ratings of goal performance and satisfaction, while scores in the other two groups did not change. At six-month follow-up, the CR group rated their memory performance more positively than did RT and NT. Behavioral changes in the CR group were supported by fMRI data for a sub-set of participants. Conclusions: The findings support the clinical efficacy of CR in early-stage AD. The study was funded by the UK Alzheimer’s Society.

F3-01-04

OCCUPATIONAL THERAPY FOR COMMUNITYDWELLING OLDER PEOPLE WITH DEMENTIA AND THEIR CAREGIVERS: FROM DEVELOPMENT TO IMPLEMENTATION

Myrra Vernooij-Dassen, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Background: Cure of dementia is not possible, but patients’ daily functioning and quality of life can be improved and caregiver burden can be reduced. Community occupational therapy proved to be one of the most effective interventions in dementia care. However, in order to be successful, the implementation of the community occupational therapy protocol should be carried out properly. Methods: The MRC framework (Campbell 2000, 2007) was used to develop and evaluate the effectiveness and cost-effectiveness of this intervention (Graff 2006, 2007, 2008), to perform a pilot implementation study on barriers and facilitators for implementation and design a recent implementation study in the Netherlands. Results: RCT (Graff et al, 2006) was effective regarding patients’ daily functioning and quality of life, mood and health status and caregiver’ sense of competence, quality

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AN INTERVENTION TOOL FOR LOWER AND MIDDLE-INCOME COUNTRIES: ‘HELPING CARERS TO CARE’

Marc Wortmann, Alzheimer’s Disease International, London, United Kingdom. Background: The numbers of people with dementia will increase in the next 40 years worldwide from 35.6 to 115.4 million. Much of the increase will take place in lower and middle-income countries. They account for 57.7% of the numbers in 2010, rising to 70.5% in 2050. There is an urgent need for tools that can be used in these countries. Alzheimer’s Disease International (ADI) is the federation of over 70 Alzheimer associations in the world and hasthe 10/66 Dementia Research Group to carry out population based research in lower and middle-income countries. This paper reports on two studies testing the effectiveness of the 10/66 caregiver intervention among people with dementia, and their carers. Methods: A simple intervention tool (including video and manuals) was developed. Two randomized controlled trials (RCT) were conducted in Russia (Moscow) and India (Goa). Mild to moderate cases with dementia and their caregivers were included. Community based intervention provided by a team consisting of Home Care Advisors who were supervised by a counselor and a psychiatrist, focusing on supporting the caregiver through information on dementia, guidance on behavior management, a single psychiatric assessment and psychotropic medication if needed. Caregiver assessment included mental health, caregiver burden, quality of life, and distress due to behavioral disturbances. Patient assessment included behavioral problems, quality of life and activities of daily living. Results: In the Moscow study, caregivers in the intervention group reported large and statistically significant net improvements at 6-month follow-up in burden compared to controls. No group differences were found on caregiver psychological distress and patient and caregiver quality of life (Int J Geriatr Psychiatry 2009 Apr 24 (4) 347-54). In the Goa study, the intervention led to a significant reduction of general health and neuropsychiatric symptoms, and non-significant reductions in caregiver burden (PLoS One 2008 Jun 4;3 (6) e2333). Conclusions: The low-level intervention seems to be as effective than similar interventions applied in high income countries. An effective tool for screening and support at home is available for lower and middle-income countries and can be obtained through ADI. There are several versions that are culturally specific for different parts of the world.

F3-01-06

THE ROLE OF SOCIAL SUPPORT IN COPING WITH THE BURDEN OF CAREGIVING: A COMPLEX RELATIONSHIP

Helene Kerherve, Broca Hospital, Paris, France. Background: The purpose of this study was, first, to investigate the caregivers’ perceived stress and perceived support on their mental health and, second, to examine moderator effects of the caregiving status (spouse