The 3rd International Symposium on Alzheimer’s Disease and Related Disorders in the Middle East, Istanbul, Turkey, October 1-2, 2005

By Friedland, Robert P Emre, Murat; Geula, Changiz

The 3rd International Symposium on Alzheimer’s disease (AD) and related disorders was held in the Middle East on October 1-2, 2005, in Istanbul, Turkey. Participants were attracted from many countries in the Middle East, including, Egypt, Greece, Israel, Jordan, Lebanon, and the United Arab Emirates. Participants also attended from Belarus, Canada, Cyprus, India, Iran, Mexico, South Korea, the USA, the UK and Turkey. The Symposium was convened by Robert Friedland of Cleveland and organized by a local committee chaired by Murat Emre of Istanbul. The 2-day program featured sessions dealing with the basic sciences of dementia, the special issues of dementia in the Middle East, genetics, epidemiology, differential diagnosis, treatment, and caregiving, with a poster session. This report highlights presentations from the meeting. The previous meeting which took place in Istanbul May, 2003 was summarized in Amyloid: J Protein Folding Disorders 2004;11:276-280. Presentations from the October 2005 meeting can be viewed at the meeting website at www.worldeventsforum.com/ alz.htm.

AD is a problem with immense worldwide implications. Life expectancy is increasing around the world and because AD doubles every 5 years after the age 65 in incidence and prevalence, it will undoubtedly become a greater problem in the future. For nearly all of human history, most people were young. It is believed that from the 21st century onward, however, most people will be old because of lower death rates. Declining death rates have been found in world populations through the 20th century, attributable to medical advances and improved standard of living. In the USA, from 1950 to 2000, the probability of surviving from age 80 to 100 increased 20- fold. These trends are found all over the world, including developing countries. AD and related disorders have received relatively little attention in countries in the Middle East, in part because the percentage of Middle Eastern populations over age 65 is lower than in North America and Europe. However, populations in the Middle East are aging just as they are everywhere else in the world.

Insights into basic and clinical neurobiology from genetic neurodegenerative diseases

The Symposium opened with a plenary lecture by Peter St. George- Hyslop of the University of Toronto on Insights into basic and clinical neurobiology from genetic neurodegenerative diseases. He outlined the genetics and biology of dementia and reviewed the three genes responsible for over 160 mutations causing familial early- onset autosomal dominant AD on chromosome 21 (amyloid precursor protein), chromosome 1 (presenilin 1), and chromosome 1 (presenilin 2). The value of identification of genes for enhancing our knowledge of disease-causing pathways was emphasized and the role of this valuable information in developing new treatments presented. He emphasized the concept that neurotoxic intracellular deposition of insoluble proteins in a beta-pleated sheet conformation was the cause of many neurodegenerative disorders. He outlined our understanding of the metabolism and catabolism of the amyloid precursor protein (AbetaPP) on chromosome 21, which contains the ABeta (Abeta) domain deposited in plaques and vessel walls and its alternate pathways of breakdown by the gamma, beta and alpha secretases.

The important mechanism of chaperoning and degradation of Abeta by neprilysin and insulindegrading enzyme was also presented. The AbetaPP breakdown product AICD may play a role in induction of factors enhancing the degradation of Ass. Dr. St. George-Hyslop also presented the various familial autosomal dominant causing mutations in the AbetaPP, which are all localized in and around the Abeta peptide domain and which increase the production of the Abeta42, species, Ass fibrillogenesis and toxicity. The mutations causing AD cause APP misprocessing. For example, the PS 1 and PS2 mutations influence the gamma-secretase cleavage enhancing Abeta production. Dr. St. George-Hyslop reviewed his important work showing that presenilin proteins form a complex with nicastrin to cleave AbetaPP and generate neurotoxic Abeta (Yu et al. Nature 2000; 407:48-54). He reviewed the role that the ApoE e4 allele plays, as the e4 protein apparently blocks removal of Abeta by LRP receptors, causing increased accumulation and aggregation into oligomeric protofibrils which may be neurotoxic. He demonstrated how patients with AbetaPP or PSl mutations have earlier disease onset when they also have the ApoE e4 allele and how animal models genetically engineered to contain AbetaPP and PSl mutations have enhanced disease compared to those with only AbetaPP mutations, confirming that known AD genes act in biochemical pathways affecting AbetaPP processing.

Methods used for gene discovery were discussed, including those that are linkage-based or determined by case-control association studies. Over 100 candidate genes have been recorded to be associated with AD but these have had a poor track record of replication. Family linkage-based methods have confirmed localization of an AD gene to a broad region of chromosome 10 and also chromosome 12. The chromosome 17 TAU gene responsible for some cases of frontotemporal dementia (FTD) was also reviewed. Dr. St. George-Hyslop discussed mutations in the TAU gene on chromosome 17Q found in 10-40% of FTD cases. These mutations disturb binding of TAU to microtubles causing accumulation of free unbound form of TAU, which aggregates into paired helical filaments. He demonstrated a pathway by which Abeta accumulation and neuronal injury causes the altered TAU metabolism found in AD. The observation mat mutations in the TAU gene cause neurodegeneration shows that TAU accumulation is a toxic event.

The application of these AD studies to prediction of future risks was discussed. At present, testing and genetic counseling are not useful for sporadic forms and conflicting data on the value of ApoE genotyping for predicting conversion of mild cognitive impairment to AD were presented. A heuristic model in which knowledge of genes will inform choice of therapy was discussed. Pathways leading to Abeta production and accumulation are valuable targets for therapies, including antibodies, blockage of the secretases and aggregation. Knowledge of both genes and exposure to environmental factors are important in determining risk. The role of environmental factors, including education, head injury, metals, and concurrent medical illnesses (including diabetes and cerebral and cardiovascular diseases) was emphasized. Work on the genetics of Creutzfeldt-Jakob disease with mutations in the PRP gene was also reviewed.

AD in the Arab world

Ashraf Al-Kurdi, FRCP, MD, from Amman, Jordan, talked about problems of AD in the Arab world, comprised of 22 countries with a common language and religion. Population estimates for Jordan were presented showing that the percentage over 60 is estimated to increase from 4.4 to 6.1% from 2000 to 2025. A few cases of dementia from the community in Jordan were reviewed to demonstrate issues of diagnosis and management. The importance for Jordan and other Arab countries to develop the resources and tools to face the socioeconomic and medical needs of an aging population was discussed. Dr. Kurdi suggested a set of recommendations on actions that must be taken by the medical community and governments to be better prepared for aging. The importance of Alzheimer’s Associations in this regard was emphasized. Dr. Kurdi believes that it is fair to conclude that the number of reported cases of AD is far less than the actual number of existing cases . . . the disease is underdiagnosed in the region. Also, many patients present in the later stages, when the prognosis is relatively worse and opportunities to benefit from drugs is impaired. Also, the view that Arab societies consider memory loss to be part of normal aging was discussed as a hurdle to overcome to ensure proper management. Major hurdles placed in the diagnosis include illiteracy, lack of validated tests, lack of interdisciplinary teams and associated co- morbid illnesses. [In order to help the lack of tests, the organizers of the meeting made available (on the meeting website www. worldeventsforum.com/alz.htm) an Arabic translation of the Mini Mental State Exam] . The goal of cross-regional collaboration and teamwork to share best practices is clear.

Dr. Kurdi discussed the fortunate strength of the family unit in the Arab world which ensures the wellbeing and care of the elderly. However, there is a need for improvement in nursing homes and day care support. Lack of statistics and solid data is one of the key issues faced in the Arab world, applicable to many conditions, including AD. These problems are related to the lack of specialized institutions (governmental or private) and the educational environment; and because the young generation of workers returning after training in the developed world return to find a heavy load of patients and administrative responsibilities. Intensive plans for research and donations to research, including tax exemptions, are needed. Genetic labs and genetic counseling are still in their infancy in Arab countries. The role of genetic and environmental factors, including pollution (particularly air quality and water contamination), were emphasized. The need for a set of recommendations and actions that must be taken by the medical community and governments towards a better preparation for brain aging was discussed. Dr. Kurdi suggested that the Pan Arab Union of Neurological Diseases should take on the challenge of creating a Pan Arab Epidemiological Study to enhance awareness and provide a base for dealing with governmental bodies. Dr. Kurdi also presented a valuable and fascinating talk on the history of neurology in Arab and Muslim countries from AD 500 to 1516. The language of science during this period was Arabic and many scientists and physicians throughout the Muslim empire taught and wrote in Arabic. Political and cultural stability throughout the Muslim empire from central Asia to Andalusia resulted in religious tolerance to allow the work of scientists to flourish. The role of Arab scholars including Ali ibn Rabban Al-Tabari (AD 838-870), the author of the first Arabic medical encyclopedia The Paradise of Wisdom, was discussed. Al- Tabari relied upon clinical experience and included references to psychotherapy. He wrote about the brain and was among the first authors to write on epilepsy and headache and the effect of psychological states on disease. He described tetanus as well as hemiplegie facial palsy and disturbances of speech associated with motor deficits. During a flourishing period (AD 900-1300), many Christians and Jews had major contributions to medicine through the tolerance of Islam. Because of the freedom to study, practice, write, and teach, their contributions were highly recognized and accepted. There was good communication between the eastern and western parts of the empire. Hospitals and libraries were established. Abu Bakr Mohammed Bin Zakariya Ar-Razi (Rhazes) (AD 841- 925) was one of the greatest doctors of the period. He wrote an important medical book, Al-Hawi (The Container) and he wrote more than 200 books and articles. Rhazes excelled in many fields, including philosophy, botany, zoology, mathematics, physics, and music. He made many anatomical discoveries, dissecting animals and noting the importance of anatomy for understanding function. He was a true humanitarian, supporting sympathetic treatment of serious illnesses and concluded that epilepsy was a disorder of the brain. He identified hemiplegia as a brain disorder whereas Galen had previously ascribed it to a problem in the ventricles. Contributions of other Arab physicians were outlined, including that of Abu Ali AI- Hussein Bin Abdallah ibn Sina (Avicenna) (AD 980-1037) who was highly respected for his contributions to medicine, producing over 276 books. He made contributions in relation to meningitis, stroke, epilepsy, and helped with the development of opium as an anesthetic. His book Al Kanoon was a principal medical text in the Arab world and in Europe for 800 years. Until the 16th and 17th centuries, every student of medicine had to master Arabic. It was on this foundation from Muslim countries that European medicine embarked on its modern renaissance beginning in the 1 7th century.

Dr. Nasser Loza from Cairo presented an elegant talk on the history of brain diseases in Egypt. He also presented an historical perspective on the burden of dementia in an extended family social network. The background in religious and moral culture of the Middle East and the importance of belief in life-after-death, and the influence of migration and war were discussed. Dr. Loza demonstrated the importance of respect for the elderly in Islamic, Christian and Jewish traditions. In particular, the Muslim teaching is that filial piety to the parents is second in importance only to “the prayer at its proper time.” Disobeying of parents is considered to be a major sin. The family structure in Egypt and the importance of aging of the Egyptian population was emphasized along with the increasing urbanization of the population and a shortage of homes for the elderly in Egypt (with an estimated 14.1 million who will have to be cared for in the community in 2030). Caregiver burden, increasing caregiver stress from behavioral symptoms, loss of activities of daily living and the implications for services and research were reviewed.

Dr. Marina V. Stoupa Hadidi of Amman, presented her experience with the diagnosis and treatment of dementia in Jordan. The low state of awareness about AD in Jordan was emphasized and the lack of data about incidence and prevalence of the disease and about various forms of dementia reviewed. Patients in Jordan are mostly treated by neurologists and psychiatrists and there are a few geriatric nursing homes. Illiteracy is a problem and is associated with low life expectancy and is a risk factor for dementia. In an analysis of 70 consecutive patients diagnosed as AD in Dr. Hadidi’s clinic, she found a mean age of 68 years, with 20% of them illiterate. Illiterate patients were more often diagnosed in the moderate or severe stages as opposed to the mild stage. Illiterate patients and their relatives were less often found to improve with acetylcholinesterase treatment. The role of hypertension, diabetes and modifiable risk factors for stroke and dementia were reviewed. Dr. Hadidi reported on the development of the new Jordanian Alzheimer’s Association, which involves professionals, caregivers and social workers and has an epidemiological study within the country that is underway.

Dr. Abeer Mahmoud Eissa of Cairo, presented studies from Egypt on sex differences in AD and other dementias. The most common form of lateonset dementia was AD. Illiteracy was common in the female group. Multi-infarct dementia was more common in men than women. The symptom profile in cognitive decline was similar in males and females but the rate of deterioration was slower in women than men and the response to medications, prognosis and mortality rate were all better in females. The possible dependence of these findings on neurobiology of estrogen and testosterone in the brain was discussed.

Dr. Doaa Hewedi of Cairo, presented her work on the quality of life in AD patients in Egypt. This is one of the first studies on quality of life in mentally ill elders in the Middle East. Dr. Hewedi studied what participants thought was meant by “quality of life” and what their areas of concern were. An Arabic version of a Quality of Life Profile for seniors was developed and studied in 70 AD subjects. Meaningful information regarding loss of independence and inability to work, difficulty with relationships and leisure activities were identified. A relationship was found between the quality of life score and symptom profile.

The importance of Alzheimer’s associations

Nori Graham, MD, former President of Alzheimer’s Disease International (ADI) in London, presented a review on the role that ADI is playing in the world (http://www.alz.co.uk/). It was founded in 1984 and currently has over 75 national members and is officially affiliated with the World Health Organization (WHO). Its goals are to build and strengthen Alzheimer’s associations throughout the globe so they can better meet the needs of people with dementia and their caregivers and to raise the world’s awareness of AD and other dementias. ADI achieves its goals through information, courses and annual conferences. It also coordinates World Alzheimer’s Day, September 21st, and encourages international research. The important services provided by national Alzheimer’s associations in providing information, running self-help groups, offering courses, advocating on behalf of patients and families, assisting in services and raising public awareness and encouraging research were discussed.

Diane Mansour of the Alzheimer’s Association of Lebanon presented developments in her country and in the Middle East on the importance of the establishment of Alzheimer’s associations. The current situation in Lebanon demonstrates poor awareness of the needs of Alzheimer’s patients and families. Ms. Mansour stressed that it is important that this work be carried out in the specific cultural and social context of the population to reach beyond the educated elite. Lebanon became a full member of ADI in 2005. Workers in Lebanon are contributing to the establishment of associations in neighboring countries. Alzheimer’s associations can change the attitude of rhe public and provide support to patients and caregivers, educate physicians and enhance the quality of care in nursing homes, as well as encourage the establishment of adult day care centers. The conference on AD in Arab world held in 2005 in Beirut can be seen on the website www. alzlebanon.org.

Dr. Jamal Khatib of Amman presented his work with the Jordanian Alzheimer’s Association to raise public awareness and study the pattern of dementia in the community. They found that 61% of subjects had had one or more mental or behavioral disturbance in the past month, particularly apathy, depression, agitation, or aggression. Patients with dementia are presented to the doctor rather late after onset of the illness in the Middle East. Most patients who present to psychiatrists have not yet been diagnosed, even though they are already behaviorally disturbed. Awareness about the illness should aim to enhance early diagnosis.

Dr. Amit Dias of the Dementia Society of Goa, India, spoke on the development of the Alzheimer’s Association of India. Problems of dementia in India are exacerbated by the social trend of breaking up of the family care system, financial difficulties and lack of homes for the aged. Many existing homes for the aged in India do not admit people with dementia. The ongoing ADI Research Program 10/66 was reviewed, including the results of the Indian site showing that dementia and depression are widely recognized but not viewed as illnesses but as a normal part of aging (Prince et al. Int J Ger Psychiat 2004;19:178-181). Some local and regional languages do not have terms to describe these disorders and elder abuse and neglect is common. The Dementia Society of Goa, formed in 2002, has focused on home care, raising awareness and building capacity for care supported by WHO. A Center for Dementia Care is being built in Goa and the economic and social needs discussed. Problems with dementia services in India include the lack of funds, lack of political commitment, other health priorities, poverty, lack of awareness, lack of professional support and age-sensitive services, and stigma. Clinical features, screening and evaluation of dementia

Dr. Amin Abuful working with Rivka Inzelberg and Robert Friedland and colleagues at the Hillel Yaffe Medical Center, Technion Rappaport Faculty of Medicine, discussed rhe influence of gender on norms of the Mini Mental State Examination (MMSE). The study conducted in the Arab community of Wadi Ara of 438 subjects without dementia, mean age of 72, found that the Brookdale Cognitive Screening Test was highly correlated to the MMSE and scores were also significantly correlated with education. The normative data for Arabic translation of the MMSE by gender was presented.

Dr. Iftah Biran from the Hadassah Hebrew University Medical Center, presented his novel analysis of the sentence question on the MMSE. Examples demonstrating the relationship between the sentence and the patient’s adaptation to illness were illustrated. It was hypothesized that the MMSE could probe psychodynamic processes and may be a measure of affective co-morbidity.

Dr. Herman Buschke of the Department of Neurology at the Albert Einstein College of Medicine in New York presented his unique view of screening tests for AD. The need for screening is emphasized because of the finding that most patients with moderate dementia are not recognized by primary care clinicians. The need for a simple, rapid and accurate screening test with good sensitivity and specificity is great. Dr. Buschke designed his screening test to use for selection of persons for diagnostic testing and not as a diagnostic test in itself (Kuslansky et al. J Am Geriatr Soc 2003;50:1086-1091). Dr. Buschke demonstrated that controlled learning and controlled recall were best to illicit maximum recall through encoding specificity and insure that decreased recall is due to impaired memory. His Memory Information Screening Test (MIS) allows for controlled learning followed by free and then cued recall. The task assures attention and equal processing and induces deep semantic processing. It allows all individuals to do the same processing to show that the required processing was done to ensure that decreased recall is due to impaired memory. Dr. Buschke demonstrated that screening for dementia depends on detection of memory impairment with good specificity and positive predictive value, as well as good sensitivity. Controlled learning with controlled recall and encoding specificity is necessary to elicit maximum recall by effective cued recall. The MIS improved screening by controlling learning and his data demonstrates there is a simple, rapid, effective and easily administered screening test with good specificity. It has been recommended by rhe American Academy of Neurology for use as a screening test for AD.

Gene environment interactions and AD

Robert Friedland from Case Western Reserve University in Cleveland, Ohio presented rhe work of his group on gene environment interactions in AD. Studies of Africans in Kenya, African Americans and Caucasians in Ohio, and Arabs in the Middle East were reviewed. Dr. Friedland pointed out that studies show that all people over 60 have amyloid in their aorta, with fibrillar deposits of medin, an integral fragment of smooth muscle cell, produced lactadherin. This and considerable other work demonstrates the propensity of proteins to fold abnormally with age. Dr. Friedland commented that mechanisms to deal with these misfolded proteins may become exhausted in neurodegenerative disorders. This may be particularly true in sporadic late-onset AD when abnormalities in Abgr; protein clearance from brain to blood and clearance from the blood may contribute to Abgr; deposition and toxicity. The epidemiology of AD in the Middle East was reviewed, with the demonstration that rhe largest age group at present in Jordan is made up of those aged 5-9, but in 2025 it will be of those people aged 30-34, with a remarkable increase in the proportion over 60.

The work of Dr. Friedland in collaboration with Dr. Lindsey Farrer at Boston University was discussed. Findings in studies of Arab subjects living in Wadi Ara in Israel were reviewed, with familial clustering and genetic linkages reported previously to sites on chromosomes 9, 10, and 12. A new angiotensin-converting enzyme polymorphism has also been recently reported (Meng et al. Am J Hum Gen 2006;78:871-877). Important environmental factors in Wadi Ara may include low levels of education and fish consumption, smoking, high-fat diet, hypertension, and physical inactivity after retirement. Dr. Friedland proposed that brain diseases with aging are due to the failure of protective mechanisms resulting from gene- environment interactions, including environmental affects on gene expression. Potential modifiable protective factors for AD and implications for public policy were discussed. They have not found any genetic abnormalities in the transthyretin (TTR) gene on chromosome 1 8 in their preliminary studies. This gene may be important in AD because TTR binds to the Abeta peptide.

Selective neuronal vulnerability in AD

Dr. Changiz Geula of Northwestern University Medical School in Chicago, Illinois, discussed the issue of selective vulnerability of specific neuronal populations to degeneration in AD. He reviewed his findings and those of others, demonstrating that the basal forebrain cholinergic neurons (BFCN) are among the first neurons to show AD- related pathology and display marked degenerative changes not only in AD, but also in most other neurodegenerative disorders of the elderly. Dr. Geula has observed phosphorylated tau accumulation and tangle formation in the BFCN very early in the course of normal aging and AD. He also presented findings indicating abnormalities in cholinergic axons within the cerebral cortex which start early in the course of normal aging and are thought to result in degeneration of these axons in AD.

Dr. Geula indicated that the reasons for the selective vulnerability of specific neuronal populations to neurodegenerative processes remain poorly understood. He advanced the hypothesis that since age is rhe main risk factor in neurodegenerative disorders of rhe elderly, age-related changes are likely to contribute to patterns of selective neuronal vulnerability in these diseases, including AD. He reviewed his findings of age-related changes in the BFCN (Wu et al. Exp Neurol 2005;195:484-496). The primate (including human), but not the rodent BFCN, are rich in levels of the calcium- binding protein calbindin-D^sub 28K^, which binds calcium with high affinity and thus regulates levels of intracellular calcium. The BFCN display a substantial, regionally and neurochemical^ specific loss of calbindin in the course of normal human aging. This loss appears to be a specific age-related phenomenon and is not related to the density of plaques and tangles that are found in the brains of some normal elderly. Based on these findings, Dr. Geula has advanced the hypothesis that the age-related loss of calbindin deprives the aged BFCN fr^m the capacity to regulate intracellular calcium, leaving these neurons vulnerable to pathological processes, such as those in AD, with the potential to cause increased levels of intracellular calcium and thus lead to degeneration due to calcium toxicity. In support of this hypothesis, Dr. Geula has produced preliminary evidence indicating that the BFCN which degenerate in AD belong to the population that lose calbindin in the course of normal aging.

Electrophysiology of dementia

Dr. Hakan Gurvit of Istanbul University presented his studies on event-related potential characteristics in early AD. He found that latency of the P3A wave, which may be an index of sustained attention, discriminated moderate from mild dementia. The P3a wave is believed to be mediated by the prefrontal cortex and is an index of novelty detection, which might be affected relatively late in AD.

Homocysteine and B vitamin chemistry in AD

Dr. Yoram Barak and colleagues in Bat-yam, Israel presented a study on folic acid deficiency in elderly psychiatric patients (Arch Gerontol Geriatr 2005;41: 297-302). He found that 16% of all new elderly admissions had folic acid deficiency. The relationship between folic acid deficiencies, high homocysteine levels in plasma in dementia was discussed and the importance of dietary intake of folic acid, Bn, riboflavin and pyridoxine was presented. These nutritional deficits may be related, of course, to cognitive decline and lack of social support as well as aging. The folate fortification of foodstuffs was recommended.

Dr. Eli Mizrahi from the Chaim Sheba Medical Center in Tel Aviv presented his work on homocysteine metabolism. In studies with Friedland and colleagues in Cleveland, they found significantly higher plasma homocysteine levels in AD patients than in controls in Wadi Ara (remaining a significant difference after adjusting for year of birth, gender and smoking status). Plasma Bi2 and folate levels, however, did not differ between patients and controls. The high levels of plasma homocysteine may suggest the need for folate and B12 supplementation in the Middle East (J Nutr Health Aging 2003;7:160-165).

Other dementias

Dr. Yuri Alekseenko from the Department of Neurology, Vitebsk, Belarus, presented work on traumatic brain injury in vascular dementia. It was found that vascular dementia patients with traumatic injury demonstrated more extensive and frequent disorders of consciousness in memory loss than younger subjects. The difficulty in distinguishing primary and secondary brain injury (due to syncope seizures or vertigo) was stressed. Dr. Alekseenko found that chronic cerebrovascular pathology decreases the “concussion threshold”, enhancing this spectrum of symptoms after brain injury. Nursing home care of dementia

Dr. Chris Messis presented his group’s work on nursing home care of dementia patients in Cyprus. The increase in aging in Cyprus, as elsewhere, was discussed. The cut-off of 20 on the MMSE was used for dementia in Cyprus. Over half of the population in nursing homes in Cyprus is demented. In many cases dementia was unsuspected and very few received anti-Alzheimer medications, even though they are available free from government sources (only 2% of subjects were taking an acetylcholinesterase inhibitor in nursing homes).

Pharmacotherapy for dementia

Dr. Diana Paleacu at rhe Abarbanel Mental Health Center in Bat Yam, Israel presented her work on Quetiapine treatment for AD. Quetiapine was found to be effective in reducing agitation in AD and was not found to enhance cognitive decline. In doses of up to 200 mg a day it improved clinical global rating scales and was generally well tolerated. The importance of non-pharmacological interventions was stressed as well as use of acetylcholinesterase inhibitors and Memantine for psychiatric disturbances in dementia.

Dr. A. Mark Clarfield from Beer-sheva Medical Center in Israel discussed ethical issues and end-of-life care from the approach of three monotheistic religions: Judaism, Catholicism and Islam. Scenarios concerning end-of-life issues were discussed. It is clear that the three religions share the principals of beneficence and non- maleficence (not to do evil). The approach of the three religions to the end-of-life issues raised by Dr. Clarfield are also remarkably consistent. Catholicism is the most open to autopsies and advanced directives. Dr. Clarfield and associates have a recent paper on this matter in the Journal of the American Geriatrics Society (2003;51:1149-1154).

Ethics and dementia

Dr. Lilia Mendoza from Mexico City discussed ethical dilemmas and human rights for people with dementia. The importance of personal values and cultural perspective on care of demented subjects was presented and the value of avoiding discrimination, stigma, ignorance, fear and silence stressed. Also, it is crucial that people with dementia have the same rights as those without. Dr. Mendoza quoted from the work of Stephen Post of Cleveland, Ohio that care must attend to the non-cognitive aspect of the self. She reviewed the problem presented by the fact that physicians are not well trained to meet the special care and needs of older people. The current thrust of ADI to include discussions with persons with dementia was reviewed as stated by Christine Bryden: “nothing about us, without us”.

The ethics of treatment of Alzheimer’s patients was reviewed by Ruth Goldberg from the Alzheimer’s Association of Israel. She discussed issues of how patients should be informed and presented the conclusion that information must be delivered after an extensive and thorough examination with information about prognosis, treatment options and support services. The patient’s concerns must be addressed and attention be paid to family dynamics. The doctor closest to the patient should deliver the information and there should be the availability of other meetings and the patient and family must have time to ask questions. Issues of driving and competence were also addressed.

Psychiatric manifestations of dementia

Dr. Isin Baral-Kulaksizoglu of Istanbul University presented her work on suicide in geriatric depressed patients in Turkey. A total of 8.6% of people in Turkey are currently over the age of 65 with life expectancy of 71 years for women and 67 for men. The elderly population in Turkey is rapidly increasing in size. A study recently published by Dr. Kulaksizoglu in the International Journal of Psychiatry (2005;17:303-312) showed a prevalence of depression of 16% of 1018 community-dwelling elderly. Elderly depression was found to be unrecognized and often untreated by medical staff. Suicide is not common in the elderly population in Turkey, which could be due to under-reporting or because it is strictly forbidden in Islam. Self-killing was found not to be an option for adults with strong religious education. It was concluded the clinicians must be careful for passive suicidal attempts, which may be difficult to recognize.

Dr. Rivka Inzelberg of the Technion in Haifa, Israel, discussed neuropsychiatrie manifestations of Parkinson’s disease, including depression, anxiety, sleep disturbances, hallucinations, psychosis and delirium. Risks for nursing home placement are very much increased by hallucinations and psychosis. Risk factors for hallucinations include cognitive impairment, daytime somnolence and long duration of disease. Patients with a family history of Parkinson’s disease were found to be more likely to have hallucinations. Visual dysfunction was also reviewed, including Dr. Inzelberg’s finding that retinal nerve fiber layer thickness is decreased in Parkinson’s disease as measured by retinal coherency tomography (Vision Res 2004;44:2793-2797).

Dr. Engin Eker of Istanbul presented his work on behavioral and psychological symptoms of dementia. Psychiatric manifestations of dementia are important because they contribute to caregiver burden and nursing home admission (Alici-Evcimen et al. Int Psychoger 2003;15:69-72). Rating scales are not always culturally appropriate. Family, friends and neighbors are extensively involved in the care of demented older persons in Turkey (mostly by spouses, eldest daughters or daughter-in-laws providing support). Families approach institutional care as a last resort. The 10/66 Dementia Group Study on Behavioral and Psychological Symptoms of Dementia in Turkey and other countries were reviewed. Regional differences were found, with high rates of agitation and wandering and sleep disturbances in India. Vocalization was common in Latin American persons and reported psychiatric effects were highest in India and lowest in China. Depression, anxiety and paranoid psychosis was more common in people from Latin America and least common in China. The need for trained general practitioners, community nurses, and social workers in this area and cross-cultural studies on psychiatric disturbances in developing countries was stressed.

Frontal-temporal lobar degeneration

Dr. Gorsev Yener from Izmir, Turkey presented her work on frontal- temporal lobar degeneration (FTLD) in a Turkish population. Four percent of patients in the Izmir Dementia Clinic of 1 1 69 patients from 1994 to 2004 were found to have frontal-temporal dementia. Most subjects with dementia had AD (67%) or vascular dementia (15). Nine percent had Lewy body dementia. From 1994 to 2001 there were 35 cases of FTLD, 25 progressive supranuclear palsy and five cortical basal ganglionic degeneration (CBD). Forty to sixty percent of FTD had a family history. More patients had a family history with FTD than with PSP, CBD or AD. The variable pathological features, including Pick bodies, TAU deposits, ubiquitinated intranuclear inclusions were presented. Subtypes related to motor neuron disease, CBD and PSP were discussed. Dementia lacking distinctive histological findings has become less common with new staining techniques. Clinical features were reviewed and the profile of clinical manifestations of FTLD in Turkey was found to be similar to that in the United States. Patients who had FTD as well as motor neuron disease were more likely to have parkinsonism.

Dr. Stavros Baloyannis from Thessaloniki presented an elegant review of the history of the brain in ancient medicine and his precise work on the morphological changes in the brain in Alzheimer’s disease (Int J Neurosci 2005; 1 1 5:965-980).

The organizers and participants of the meeting are grateful for the support of the NIH, Alzheimer’s Association USA, the Institute for the Study of Aging, Kobe Alcoa, the Joseph And Florence Mandel Research Fund, and Pfizer, Inc.

The next meeting of the group will be in Athens, Greece (4th International Symposium on Alzheimer’s Disease in the Middle East), October 26-28, 2007.

Robert P. Friedland

Department of Neurology, CASE School of Medicine

Cleveland, OH 44106-4962, USA

216 368 1913

robert.friedIand@case. edu

Murat Emre

Department of Neurology, Istanbul Faculty of Medicine

Istanbul University

4390 Capa Istanbul, Turkey

Changiz Geula

Feinberg School of Medicine

Northwestern University

Cognitive Neurology and Alzheimer’s Disease Center

Chicago, IL 60611, USA

c-geula @northwestern. edu

Copyright Taylor & Francis Ltd. Jun 2007

(c) 2007 Amyloid. Provided by ProQuest Information and Learning. All rights Reserved.