Gillian Hayes

A pilot study of potential brain donor satisfaction and attitudes towards telephone assessment

Test the feasibility of assessing cognition, psychiatric symptoms and daily living skills of potential brain donors by telephone and compare satisfaction and attitudes across telephone and face‐to‐face assessment.

Factors affecting withdrawal and donation attrition in the brains for dementia research cohort

To measure two forms of attrition in a cohort of volunteer brain donors: Withdrawal during life and non‐donation at death. To test whether cognitive impairment independently predicts attrition.

AN INTEGRATED APPROACH TO U.K. BRAIN BANKING ALLOWING RESEARCHERS TO SELECT TISSUE WITH PRECISION: MRC U.K. BRAIN BANK NETWORK, CSOLS TRACKING SYSTEM AND BRAINS FOR DEMENTIA RESEARCH

Results: The longitudinal and transitional nature of a readiness cohort creates the risk of the cohort and its concatenated trials becoming a ‘fish trap’ for its participants. With every step further into such a research project, it becomes more difficult for a participant to go back or retract from participation. Therefore, we recommend an adapted stagedconsent model for concatenated projects like EPAD, which are extended over time and multi-staged, and in which participants and data move from one stage to the next. This consent model feeds relevant information, bit by bit, along research participants’ journey, and asks informed consent at every moment in which important decisions need to be made by participants. Although informed consent is always given for a specific stage of the research project, information about the ‘totality of the project’ must always and explicitly be part of the informed consent process. Conclusions: It is critical to the success of readiness cohorts to carefully align ethical guidance for recruitment and informed consent. The ELSIwork package of EPAD recommends an adapted staged-consent model. This model may also be of value to other research collaborations in the process of developing and using readiness cohorts in Alzheimer’s disease research.

ANALYSIS OF PARTICIPANTS WITHDRAWING FROM A COHORT CONSENTING TO BRAIN DONATION AT DEATH AND DETAILED PSYCHOMETRIC ASSESSMENTS DURING LIFE

Despite no statistical significance, patients atMCI stagewithLODpresented a higher percentage of AD pathology in comparison with those having EOD. A relevant issue regards whether patients with AD pathologyatMCI stage, in the co-occurrenceofdepression, couldpresent a more aggressive course of the disease than thosewithout depression. Another important point regards if depression constitutes a predictor of clinical deterioration, including dementia, independently of the occurrence of AD pathology. To increase the sample number and to explain the aforementioned issues are the next steps of the present investigation. (1) Forlenza et al., AlzheimersDement, 2015;1:455-463. Laboratory of Neuroscience (LIM-27), IPq-FM-USP, Brazil.

BRAINS FOR DEMENTIA RESEARCH: CONCORDANCE OF CLINICAL AND NEUROPATHOLOGICAL DIAGNOSES IN DECEASED PARTICIPANTS

cases, partial agreement in 38% and discordance in 23%. In most cases where total or partialagreement occured,Alzheimer disease was the common diagnosis, followed by mixed Alzheimer/vascular dementia. Conclusions: There was good agreement between clinical and neuropathological diagnosis in the majority of cases in this sample. This affirms the accuracy of current diagnostic techniques for dementia. It is hoped that further refinement in clinical diagnosis will improve this in the future.

Brains for Dementia Research: MMSE profile of the living cohort

Background: Brains for Dementia Research (BDR) is a network of six UK brain banks/collection centres that aims to address the shortage of highquality post-mortem brains from people with dementia and suitable control cases and provide researchers with detailed clinical information on each case. Post-mortem brains are critical to our understanding of neurodegenerative processes in dementia and the underlying causes of the symptoms observed. With increasing research sophistication two things are clear: (1) the value of relating clinical information obtained during life to post-mortem biochemistry, and (2) genetic association studies require large numbers of samples from clinically, histopathologically and biochemically characterised tissue. Since BDR began in 2008 nearly 1,800 people in the UK have signed up to take part in regular assessments and agreed to donate their brain. Methods: For those with a diagnosis of dementia the following tests of memory, noncognitive behavior, mood and function will be undertaken: Mini Mental State Examination, Montreal Cognitive Assessment (MoCA), Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-Cog), Clinical Dementia Rating, Neuropsychiatric Inventory, Bristol Activities of Daily Living Scale, Cornell/Geriatric Depression Scale, Hachinski Ischaemic Scoring System Sensory/Motor Impairment. For controls, the same panel of tests will be used with the option of employing the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) cognitive battery. These tests will berepeated annually for those with a diagnosis of dementia, while the frequencyfor those without dementia will every 2 to 5 years. Results: The average age of the living cohort is 76 made up of 547 males and 986 females. Approximately 21% (329) have a diagnosis of dementia. 55% of the cohort had MMSE values obtained in the last 3 years. The distribution ofMMSE scores is shown in Figure 1.Conclusions: This is a cohort of highly motivated individuals, the majority of whom are self referring, prepared to take part in other appropriate clinical studies, and provide a valuable source of brain donations.

Brains for Dementia Research: Providing human tissue for dementia research to promote understanding of pathogenesis and aid drug discovery

Background: Brains for Dementia Research (BDR) is a network of six UK brain banks/collection centres that aims to address the shortage of highquality post-mortem brains from people with dementia and suitable control cases and provide researchers with the help they need to access the tissue. Post-mortem brains are critical to our understanding of neurodegenerative processes in dementia and the underlying causes of the symptoms observed. With increasing research sophistication the availability of tissue from individuals treated with dementia medication confirms the impact of treatment on pathology, which can inform future therapeutic research. Thus the need for quality post mortem brain tissue and the requirement for greater standardisation between brain tissue banks collaboratively providing samples remains high. Methods: Brain tissue from a range of dementias and healthy controls that have significant clinical, neuropathological and psychometric assessment information is available through BDR. Researchers worldwide can contact us or use an online tissue database to find tissue (www. brainsfordementiaresearch.org.uk) and complete a single tissue application form across all participating banks. Researchers can informally discuss requirements in terms of cases and tissue format prior to applying for tissue. Ongoing recruitment of potential donors occurs through self refer or contact through clinics and existing cohorts. Results: Brain tissue available: over 500 well characterised, high quality cases from a range of dementias and controls are available for researchers. Potential brain donors: more than 1200 clinically assessed participants aged 65 and over, 70% of which are healthy controls, projected to expand to 2500. Tissue distributed: since January 2010 we have processed approximately 30 tissue requests which could not be met by individual tissue banks, including contributing to a large GWAS study. What is welcome is that about 10% of tissue applications are from researchers who have not previously used human brain tissue. Conclusions: This initiative of the Alzheimer’s Society and Alzheimer’s Research Trust has been welcomed by those affected by dementia and their families. BDR is an easy route for researchers to access tissue needed for their studies, and in particular will help those researchers not workingwithin neuropathology departments.

Brains for dementia research providing human tissue for dementia research to further understanding and aid treatment discovery

Background: For a hundred years post-mortem brains have played a pivotal role in our understanding of the neurodegenerative processes occurring in dementia and provided significant clues as to the underlying causes of the symptoms observed. As approaches have become more sophisticated two things have become clear: (1) the value of relating clinical information obtained during life to post-mortem biochemistry, and (2) genetic association studies require large numbers of clinically, histopathologically and biochemically characterised tissue, underscoring the need for greater standardisation between brain tissue banks. Brains for Dementia Research (BDR) is a network of six UK brain banks/collection centres that aims to address the shortage of high-quality post-mortem brains frompeoplewith dementia and suitable control cases and provide researchers with the help they need to access the tissue. Methods: BDR planned brain donation programme includes regular cognitive, psychological and activity tests during life, with standardised procedures for brain donation, histopathological classification, storage and distribution. Potential donors can self refer directly or be contacted through clinics and existing cohorts. Researchers from any part of theworld can contact us or use an online searchable tissue database to find the tissue they need (www. brainsfordementiaresearch.org.uk) through a single tissue application form across all participating banks. In addition, BDR ethical approval includes devolved authority to review and approve tissue applications from the UK. Results: To date the coordinating centre has over 1250 enquiries, about 70% of which are healthy controls, with over 900 participants over 65 registered and clinically assessed. The brain banks provided additional cases so the tissue database contains over 400 well characterised cases available to researchers.Conclusions: This large joint initiative of the Alzheimer’s Society and Alzheimer’s Research Trust has been welcomed by those affected by dementia and their families, as seen in the numbers self-referring to participate. There is some evidence that this system is already proving an easier route for researchers to access tissue needed for their studies, and in particular will help those researchers not working within neuropathology departments.