Proposed mental incapacity law reform in England — What ethical and legal issues arise for demented people and their carers?

Poster Presentution:

S248

ETHICAL GUIDELINES IN BRAIN BANKING OF NEURODEGENERATIVE AND PSYCHIATRIC DISORDERS Rivkn Rmid,

Nvrherlunds

Bruin

Bank,

Amterdum

Netherlund.\

Brain Bank organizatlona serve as a valuable source of well charactenred tissues of the central nervous system, obtained via donor programs which are supplied for nrurobiological research. Brain tisrue. serum and cerebra-spinal fluid (CSF)obtained at autopry from patients with neurological and psychiatric disorder7 is wed to elucidate the various disease ethiologies. To create and develop the right infrastructure underlying brain bank activitie?, worldwide. one should have a medico-legal and ethical support system which abides to local le&i?lation. Brain banks operate in the framework of local legal and ethical guidelines considering the following aspect?; I. ti\we procurement 2. tissue management 3. tissue dissemination 4. confidentiality 5. ‘financial gain’ 6. genetic testing and counselling Brain Banks offer a unique collection of clinically and neuropathologically well documented material for investlgating neurodegenerative and psychiatric diseases. The Netherlands Brain Bank (NBB) had a unique rapid autopsy \y\tem which incorporates all the above ethical and legal guidelines in a well functioning donor program. based on informed consent of next-of-kin. This bank operates on the baais of research applications and has supplied m the past IS year %implrs from 2200 autopsies for 345 research projects in 2 I countries worldwde. We abide by the international ethical requirements and activate the local medical ethical committees for the implication of these guidelines wth the appon of our donors. We are fully aware of the international discussions being considered with respect to ownership of the obtained tissues for scientific research and possible commercial use and we currently establishmg the ethical guidellmes for the European Brain Bank Network. The NBB takes great care in securing the safe handling, storage and dissemmatmn of port-mortem tissues to basic scientists and clinicians involved in research on neurological and psychiatric disorders. Ethical issues are today one of the main concerns of the medical and biomedical community dealing with the neurological practice;crystallisin& an international consensus on the ethical and legal i\wcs is a major task at the moment.

PROPOSED MENTAL INCAPACITY LAW REFORM IN ENGLAND - WHAT ETHICAL AND LEGAL ISSUES ARISE FOR DEMENTED PEOPLE AND THEIR CARERS?

In October I999 the Lord Chancellor in England introduced proposals for far reaching reform of the law relatmg to Mental Incapacity. Thib is presently an area of great uncertainty and ambiguity. as there is a major gap in the law which interacts wth ethical debate. Hi\ proposals stemmed from considerable work from the English Law Commlssmn on the topic but rejected parts of their suggestions. This presentation wll diwuaa the considerable ethical implications (and legal issues) which look likely to nn\e with the plopoaed new law on Mental Incapacity as it may impact on dementia wfferers and their carers. The dixusamn wdl be set m the context of data recently collected. and currently due to he analyzed. concerning the frequency with which old people with dementia in Nottmgham are compulsorily detained under the Mental Health Act and the crcurn\tance\.

Poster Presentation:

Genetic Studies IV

Genetic Studies IV

were diagnosed with dementia. Presence of the APOE-t4 gene was more common among subjects with dementia. The relation between free recall on a test of verbal memory (the Buschke Cued Recall Test), and APOE gene status was examined for those subjectr who had completed the neuropsychological testing. This included 379 NC1 subjects (310 ~4.; 69 ?? 4+), 121 CIND subjects (168 ~4.; 53 ?? 4+), and 60 demented subjects (36 ?? 4-; 24 ?? 4+). Repeated-measures multivariate analyses of covariance were used to account for age, education and sex. APOE-~4 status was associated with poorer recall only m the analysis of the NC1 subjects (F=20.18, p.001). This association between APOE gene statu and memory test performance in those who did not Ehow clinical evidence of cognitive impairment or dementia suggests that both may reflect aqpectc of the same underlying process. Followup of these subjects will determine if having the APOE-~4 gene unrl performing poorly on memory tests iy associated with a higher probability of pro&resGon to dementia.

I333

N ACETYLTRANSFERASE GENERATLvE DISEASES

AS A RISK FACTOR IN NEURODE-

The importance of environmental factors in the development of Alzhiemera’ disease(AD been implied by several studies.Susceptibility of tissue\ to damage via metabolism of xenobiotics in the body may lie in the ewymes responsible for such processes. N-acetyltransferase (NAT2)has been suggested as one enzyme that could be involved in the neurotoxic processes leading to AD and other neurodegenerative dixasea. AimTo examine the possibility that a significant assocratmn exists between NAT2 genotype and the development of AD or other common neurodegenerative conditions: ADlDlffuse Lrwy Body diaeaae(AD/DLBD) AD/ Parkinron’s disease(AD/PD) AD/Vascular dwxw(AD/VaD) VaD and PD. A4rthod.s: In this retrwpective cace/control study wr examined 433 brains from three different centres in the UK: I3 I controls and 402 wffering from a neurodegenerative condition. A definitive diagnosis was obtained according to the accepted criteria for each condition. NAT2 genotyping was performed using DNA extracted from frozen bran tissue followed by a one-step PCR reaction and restriction enzyme digestion to identify the presence of 4 common pomt mutations: *4, *5, *6 and *7. Apolipoprotein E(ApoE) genotyping was also performed. Reults: Univariate analysis showed that there was a significant 1 in the fast metaboliser *4 allele in AD and PD (p=O.O29 and 0.0078) with a concomittant t in *b(AD)and *5 in PD. Differences could also hc wen between AD and ADIVAD. Stratification of the groups accordmg to NAT2 genotype although not statistically signiticant due to small numbers in some groups showed clear trend\ m genetic profiles. PD had a statistically significant J m fast acetylators vs. control (p=O.O09S).Further sub-division of the groups according to ApoE~4 status revealed a 1 in fast acetylators m the t4 negative group m conditions with Lewy body pathology. Logistic regression analys~c confrmed “6 a\ a risk factor for AD and slow, metaboliser ytntus with PD. Conclusion:This Etudy indicate\ a Ggnificant involvement of NAT2 in several forms of neurodegenerative disease. Speafic NAT2 genotype profiles could be used to identify those suffering from dementia with multiple pathology. These findings may have an effect on treatments. Bockground:

CAN THE INTERACTION (11361(APOE) GENOTYPE AND

BETWEEN APOLIPOPROTEIN E GENDER BE USED TO IDENTIFY

DIFFERENT DEMENTIAS? APOLIPOPROTEIN E GENE STATUS AND NEUROPSYCHOLOGICAL TEST PERFORMANCE IN A POPULATION-BASED SAMPLE OF ELDERLY CANADIANS. of atleast oneApoE t4 allele are hnown to be at greater rish ol developing Alzhiemers’ disease(AD). There is also evidence to suggest that women are at greater risk than men. Studies examining interactions between t4 and gender are however limited and require further investigation not only in AD but in other drmenting conditiona. AimTo examine the possibility that a significant interaction exists between gender and ApoEc4 status in AD and other dementing conditions and thiq may be a useful tool in identifying dementia5 with mixed pathology. Mefhods:In this retrospectwe case/control study we examined 479 brains from three different centres in the UK: 132 controls and 347 suffering from a neurodegenerative condition. Each brain was examined by an experienced neuropathologist and given a definitive diagnosis according to the accepted criteria for each condition. ApoE genotyping was performed using DNA extracted from frozen brain tissue followed by a one-step PCR reaction and rertriction enLyme digestion. Results: Univariate analysis showed that ApoEd status had a significant association with AD(p
In addition to advanced age, the presence of the t4 allele of the Apolipoprotein E (APOE) gene and poor performance on neuropsychological tests of memory. are two leading risk factors for AlLheimer’a disease (AD). What remams unclear, 15 whether thew two risk factors are related. Do persons without dementia who have the APOE-~4 gene perform less well on neuropsychological test?‘? We examined thi\ question in a population-based sample of people over the age of 64. All subjects were enrolled in the Canadian Study of Health and Aging, a nationwide study of the prevalence of dementia that involved over 10,000 people. APOE gene status was determined in I578 of whom I I88 had no ~4 allele and 390 had at least one ~4 allele. Subjects were assessed using mental status screening and a medical and family history. A subset of the sample also completed a physical and neurological exam and a battery of neuropsychologtcal tests. Toðer, the physician, nurse and psychologist who assessed each ubject assigned a consensus diagnosis. Of the 157X wbject? wth known APOE gene status, II23 had no cognitive impairment (NCI). 268 were identified a\ having some cognitive impairment but not dementia (CIND). and I87