Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

Local area network inhibition: a model of a potentially important paraepileptic pathomechanism in neuropsychiatric disorders.

Electroencephalographic abnormalities in the absence of any other major laboratory or imaging findings are a frequently encountered phenomenon in many psychiatric disorders. In some cases, clear-cut interictal epileptiform EEG abnormalities in patients with classic primary psychiatric disorders lead to referrals to epilepsy departments for diagnostic evaluation. Although video/EEG telemetry in these cases generally proves that there is no direct temporal link between the EEG pathologies and psychiatric symptoms, and therefore the psychiatric syndrome cannot be regarded as epilepsy, the relevance of the EEG abnormalities remains open to discussion. In this article we put forward the model of a paraepileptic pathomechanism, which might explain the pathogenetic role of such EEG pathologies, at least in subgroups of such patients. We propose that ictal or nonictal epileptic neurophysiological activity can lead to local area neuronal network inhibition (LANI). In this model clinical symptoms are related not to the excitatory epileptiform abnormalities themselves, but to the extent, site, and dynamics of the resulting local neuronal network inhibition. The LANI hypothesis is capable of explaining the complex relationship between EEG abnormalities and clinical symptoms in different neuropsychiatric syndromes and can be verified and falsified in empirical research.

Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey.

BACKGROUND: Studies have suggested that the prevalence of dementia is lower in developing than in developed regions. We investigated the prevalence and severity of dementia in sites in low-income and middle-income countries according to two definitions of dementia diagnosis. METHODS: We undertook one-phase cross-sectional surveys of all residents aged 65 years and older (n=14 960) in 11 sites in seven low-income and middle-income countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Dementia diagnosis was made according to the culturally and educationally sensitive 10/66 dementia diagnostic algorithm, which had been prevalidated in 25 Latin American, Asian, and African centres; and by computerised application of the dementia criterion from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). We also compared prevalence of DSM-IV dementia in each of the study sites with that from estimates in European studies. FINDINGS: The prevalence of DSM-IV dementia varied widely, from 0.3% (95% CI 0.1-0.5) in rural India to 6.3% (5.0-7.7) in Cuba. After standardisation for age and sex, DSM-IV prevalence in urban Latin American sites was four-fifths of that in Europe (standardised morbidity ratio 80 [95% CI 70-91]), but in China the prevalence was only half (56 [32-91] in rural China), and in India and rural Latin America a quarter or less of the European prevalence (18 [5-34] in rural India). 10/66 dementia prevalence was higher than that of DSM-IV dementia, and more consistent across sites, varying between 5.6% (95% CI 4.2-7.0) in rural China and 11.7% (10.3-13.1) in the Dominican Republic. The validity of the 847 of 1345 cases of 10/66 dementia not confirmed by DSM-IV was supported by high levels of associated disability (mean WHO Disability Assessment Schedule II score 33.7 [SD 28.6]). INTERPRETATION: As compared with the 10/66 dementia algorithm, the DSM-IV dementia criterion might underestimate dementia prevalence, especially in regions with low awareness of this emerging public-health problem.

The 10/66 Dementia Research Group's fully operationalised DSM-IV dementia computerized diagnostic algorithm, compared with the 10/66 dementia algorithm and a clinician diagnosis: a population validation study.

BACKGROUND: The criterion for dementia implicit in DSM-IV is widely used in research but not fully operationalised. The 10/66 Dementia Research Group sought to do this using assessments from their one phase dementia diagnostic research interview, and to validate the resulting algorithm in a population-based study in Cuba. METHODS: The criterion was operationalised as a computerised algorithm, applying clinical principles, based upon the 10/66 cognitive tests, clinical interview and informant reports; the Community Screening Instrument for Dementia, the CERAD 10 word list learning and animal naming tests, the Geriatric Mental State, and the History and Aetiology Schedule - Dementia Diagnosis and Subtype. This was validated in Cuba against a local clinician DSM-IV diagnosis and the 10/66 dementia diagnosis (originally calibrated probabilistically against clinician DSM-IV diagnoses in the 10/66 pilot study). RESULTS: The DSM-IV sub-criteria were plausibly distributed among clinically diagnosed dementia cases and controls. The clinician diagnoses agreed better with 10/66 dementia diagnosis than with the more conservative computerized DSM-IV algorithm. The DSM-IV algorithm was particularly likely to miss less severe dementia cases. Those with a 10/66 dementia diagnosis who did not meet the DSM-IV criterion were less cognitively and functionally impaired compared with the DSMIV confirmed cases, but still grossly impaired compared with those free of dementia. CONCLUSION: The DSM-IV criterion, strictly applied, defines a narrow category of unambiguous dementia characterized by marked impairment. It may be specific but incompletely sensitive to clinically relevant cases. The 10/66 dementia diagnosis defines a broader category that may be more sensitive, identifying genuine cases beyond those defined by our DSM-IV algorithm, with relevance to the estimation of the population burden of this disorder.

Prevalence, patterns, service needs, and assessment of neuropsychiatric disorders among people with epilepsy in residential care: validation of the Neuropsychiatric Inventory as a caregiver-rated measure of neuropsychiatric functioning in epilepsy.

We assessed 228 people with epilepsy (PWE) in the residential care setting using the Neuropsychiatric Inventory (NPI) and Brief Psychiatric Rating Scale (BPRS) as caregiver- and observer-rated instruments. There was a significant burden of psychopathology, about half of all subjects surveyed scoring positive on either or both instruments. Psychopathology as measured by the NPI and BPRS was significantly greater in cognitively impaired subjects than in those with intact cognitive function. The NPI was found to be a valid caregiver-rated measure of psychopathology in PWE, with a principal components analysis yielding a reliable and interpretable four-factor solution, psychosis, interictal dysphoric disorder, depression, and anxiety being identified. Mental health service needs were found to be considerable in this population, with a significant hidden burden of psychiatric comorbidity. As this population has ongoing service needs through the life span, further research is necessary.

Are patients with somatization disorder highly suggestible?

OBJECTIVE: High suggestibility is widely regarded as an important feature of patients with medically unexplained symptoms (MUS), particularly those with multiple MUS [i.e. somatization disorder (SD)], although there are few empirical data attesting to this assumption. A study was therefore conducted to compare levels of non-hypnotic suggestibility in patients with SD and medical controls. METHOD: A modified version of the Barber Suggestibility Scale was administered to 19 patients with SD and 17 controls with an established organic dystonia. RESULTS: Patients with SD were no more suggestible than control patients. Dystonia controls were more likely to deliberately comply with suggestions than the SD patients. CONCLUSION: Contrary to popular belief, high suggestibility is not necessarily a feature of SD.

The protocols for the 10/66 dementia research group population-based research programme.

BACKGROUND: Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. METHODS/DESIGN: Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. DISCUSSION: The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met.

The classification of neuropsychiatric disorders in epilepsy: a proposal by the ILAE Commission on Psychobiology of Epilepsy.

The classification of psychiatric disorders in epilepsy has evolved considerably from the first attempts in the 19th century. A dedicated subcommission of the ILAE Commission on Psychobiology of Epilepsy (now the Commission on Neuropsychiatric Aspects) has developed this classification proposal. The aim of this proposal is to separate disorders comorbid with epilepsy and those that reflect ongoing epileptiform activity from epilepsy-specific disorders, and to attempt to subclassify the epilepsy-specific disorders alone. Further, the classification of epilepsy-specific psychiatric disorders has largely followed their relationship to the ictus, with factors such as relationship to antiepileptic drug (AED) change being coded as additional information. Finally, this proposal presents a clinical and descriptive system of classification rather than an etiological classification on the grounds that there is currently inadequate information for the latter approach to be employed globally.

The complex relationship between seizures and behavior: an illustrative case report.

Epilepsy and behavior have a complex, often intriguing relationship. We report here the interesting case of Mrs. A, who presented with depression and developed seizures and an ictal psychosis precipitated by use of a selective serotonin reuptake inhibitor. She subsequently presented with forced normalization characterized by affective somatoform and hysterical manifestations.

Prevalence of Parkinson disease in Singapore: Chinese vs Malays vs Indians.

OBJECTIVE: To investigate the prevalence of Parkinson disease (PD) in Singapore and compare the rates between Singaporean Chinese, Malays, and Indians. METHODS: A three-phase community-based survey among a disproportionate random sample of 15,000 individuals (9,000 Chinese, 3,000 Malays, 3,000 Indians) aged 50 years and above who live in central Singapore was conducted. In phase 1, trained interviewers conducted a door-to-door survey using a validated 10-question questionnaire. In phase 2, medical specialists examined participants who screened positive to any of the questions. Participants suspected to have PD had their diagnosis confirmed in phase 3 by a movement disorders specialist. RESULTS: The participation rate was 67% among 22,279 eligible individuals. Forty-six participants with PD were identified of which 16 were newly diagnosed cases. The prevalence rate of PD for those aged 50 and above in Singapore was 0.30% (95% CI: 0.22 to 0.41), age-adjusted to US 1970 census. The prevalence rates increased significantly with age. The age-adjusted prevalence rates among Chinese (0.33%, 95% CI: 0.22 to 0.48), Malays (0.29%, 95% CI: 0.13 to 0.67), and Indians (0.28%, 95% CI: 0.12 to 0.67) were the same (p = 1.0). CONCLUSIONS: The prevalence of PD in Singapore was comparable to that of Western countries. Race-specific rates were also similar to previously reported rates and similar among the three races. Environmental factors may be more important than racially determined genetic factors in the development of PD.

Religiosity is associated with hippocampal but not amygdala volumes in patients with refractory epilepsy.

OBJECTIVE: To assess the relationship between the behavioural triad of hyper-religiosity, hypergraphia and hyposexuality in epilepsy, and volumes of the mesial temporal structures. METHOD: Magnetic resonance images were obtained from 33 patients with refractory epilepsy and mesial temporal structure volumes assessed. Amygdala and hippocampal volumes were then compared in high and low scorers on the religiosity, writing, and sexuality sub-scales of the Neurobehavioural Inventory. RESULTS: Patients with high ratings on the religiosity scale had significantly smaller right hippocampi. Religiosity scores rated by both patient and carer showed a significant negative correlation with right hippocampal volumes in this group. There were no other differences in amygdala or hippocampal volumes between these groups, or between high and low scorers on the writing and sexuality sub-scales. CONCLUSIONS: These findings suggest that right hippocampal volumes are negatively correlated with religiosity in patients with refractory epilepsy.

Psychopathological profile in patients with severe bilateral hippocampal atrophy and temporal lobe epilepsy: evidence in support of the Geschwind syndrome?

Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible causal element in various neuropsychiatric disorders, in particular depressive disorder and schizophrenia. To test the hypothesis that bilateral symmetrical severe volume loss of the hippocampi is of causal relevance to these psychiatric syndromes rather than an epiphenomenon we assessed the psychopathology in a group of patients with temporal lobe epilepsy (TLE) and very severe bilateral symmetrical hippocampal atrophy and compared it with that of a patient control group. Patients with TLE and hippocampal volumes smaller than three standard deviations below the mean of a control population were identified and compared with a matched patient population with normal hippocampal volumes. Psychopathology was assessed by blinded trained psychiatrists using the Present State Examination and Neurobehavioral Inventory. The prevalence of psychiatric syndromes was high in both patient groups; however, there was no significant difference between the two groups. With use of the more specific Neurobehavioral Inventory a psychopathological pattern reminiscent of the Geschwind syndrome emerged when patients with BHA were characterized by caregivers. While BHA does not result in an increased prevalence of specific psychiatric syndromes, specific symptoms that characterize the Geschwind syndrome like hypergraphia and hyposexuality might be pathogenically related to hippocampal atrophy.

Research in epilepsy: development priorities for developing nations.

PURPOSE: To identify research priorities in epilepsy for developing nations. METHODS: A panel discussion with audience participation at the Indo-U.K. Workshop on Epilepsy. This included short presentations by panelists, the presentation of a research proposal, and debate on research priorities. RESULTS: The need to focus on primary-care populations; to use a multi-centre random block design; to incorporate rural areas and a service component; to study incidence, natural history, and aetiology; to focus on problems, such as cysticercosis, and to adopt a comprehensive public health-centred approach in doing so; to study disorders of local interest, such as hot water epilepsy; to pilot both pharmacological and nonpharmacological interventions; to incorporate comprehensive measures of cognition, behaviour, and psychosocial outcome in all studies; and to examine the role of novel diagnostic tools (imaging for example) and therapy (surgery for example) on cost were all outlined as priority areas. DISCUSSION: There is a felt need for greater and better-quality research output from the developing world. The development of uniform research protocols, the twinning of developed and developing nations for research, and training of developing nations' personnel are likely to increase research output in the years that come.

Neuropsychiatric disorders in epilepsy: some transcultural issues.

PURPOSE: To review transcultural perspectives in the neuropsychiatry of epilepsy. METHODS: Systematic literature searches of standard databases, cross-referencing, chapters, and opinion leader articles. RESULTS: Articles from the Indian subcontinent, Africa, and Japan were identified and are reviewed herein. The spectrum of psychopathology in epilepsy is rather similar across cultures. However, psychopathology specific to epilepsy, the interictal behavioural syndrome of Geschwind, for example, has not been well studied outside the Western world. DISCUSSION: There is a need for well-designed epidemiological studies of neuropsychiatric disorders in epilepsy. These should use harmonised protocols and outcome measures. Special attention should be paid to the impact of aetiology on psychiatric co-morbidity and disablement.

Forced normalization at the interface between epilepsy and psychiatry.

In 1953, Landolt described a group of patients with poorly controlled epilepsy who had psychotic episodes associated with remission of their seizures and disappearance of epileptiform activity on their EEGs. He called this phenomenon "forced normalization." Since then, neurologists and psychiatrists have been intrigued by this phenomenon, and although it has been also reported by others, its existence continues to be the source of much debate. In this article, we review the clinical characteristics and potential pathogenic mechanisms of forced normalization and illustrate the complexities inherent in reaching this diagnosis, as well as its differential diagnosis in two representative cases.

Psychiatric issues in epilepsy.

In recent years there has been considerable research interest at the interface between epilepsy and psychiatry. Topics of interest include the epidemiology of psychiatric co-morbidity in epilepsy; clinical syndromes at this interface and their classification; the relationship between cognitive dysfunction and psychiatric co-morbidity; biological mechanisms that mediate such co-morbidity, especially with developments in imaging and genetic research; the association between temporal lobe surgery, vagus nerve stimulation, and other non-pharmacological treatments, and the development of such co-morbidity; the contribution of anticonvulsant drugs towards the development of psychiatric co-morbidity; quality of life and other psychosocial issues; and non-epileptic attack disorder. In this review, papers on these psychiatric issues in epilepsy, with a focus on those published in the past year (October 1999 to October 2000) are critically evaluated, and some important current issues at this interface are considered in detail.

Psychiatric outcome after temporal lobectomy: a predictive study.

PURPOSE: The occurrence of psychiatric symptoms after temporal lobectomy is well documented. The aim of the present study was to identify preoperative factors that predict postoperative psychiatric outcome. METHODS: We studied the case notes of 121 patients (from an initial sample of 167) who underwent temporal lobectomy at the National Hospital of Neurology and Neurosurgery, Queen Square, London, between 1988 and 1997. Data concerning gender, laterality of lesion, pathology, seizure outcome, psychiatric history, psychiatric outcome, resection volume, telemetry, and MRI scans were systematically collected. Factors that predict the occurrence of postoperative psychiatric symptomatology were investigated using correlational, chi(2), and logistic regression techniques. RESULTS: Poor postoperative psychiatric outcome in general was positively associated with preoperative bilateral independent spike discharges at telemetry. The size of surgical resection was positively correlated with the occurrence of postoperative emotional lability. The laterality of the epileptogenic lesion was not associated with a poor psychiatric outcome. Developmental lesions were associated with a good psychiatric outcome at a marginally significant level. Patients with a preoperative psychiatric history and de novo psychiatric symptomatology had a poorer surgical outcome in terms of seizure frequency, also at a marginally significant level. A significant correlation was found between a past psychiatric history and seizure outcome. CONCLUSIONS: We identified a high frequency of psychiatric symptoms both before and after temporal lobectomy, demonstrating that it is not a benign procedure from the point of view of psychopathology. Our results show that there are certain predictive factors that may help identify patients most at risk for postoperative psychiatric disorders.

Fixation-off sensitivity as a model of continuous epileptiform discharges: electroencephalographic, neuropsychological and functional MRI findings.

A case of fixation-off sensitivity (FOS) in an asymptomatic adult is presented and studied as a model for continuous epileptiform discharges. Video-electroencephalographic (EEG) revealed continuous bilateral occipital spike wave discharges during elimination of central vision, which were shown to be associated with transitory cognitive impairment demonstrated by neuropsychological testing. Functional MRI showed activation of parieto-occipital and frontal brain areas during the fixation-off discharges. This localization was confirmed with 64-channel EEG source analysis. The applied methods provided additional information on the pathophysiology of epileptiform discharges.