Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania.

Background: Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients.

Methods: This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets.

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

Background: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects.

Correction to: Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study).

An amendment to this paper has been published and can be accessed via the original article.

Diagnostic Biomarkers for Alzheimer's Disease Using Non-Invasive Specimens.

Studies in the field of Alzheimer's disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage-before critical neurons are lost.

Computerised cognitive training for 12 or more weeks for maintaining cognitive function in cognitively healthy people in late life.

Background: Increasing age is associated with a natural decline in cognitive function and is the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or that reduce the risk of dementia is a research priority.

A roadmap to develop dementia research capacity and capability in Pakistan: A model for low- and middle-income countries.

Objective: To produce a strategic roadmap for supporting the development of dementia research in Pakistan.

Background: While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan.

Methods: We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan.

Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study).

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo.

Computerised cognitive training for preventing dementia in people with mild cognitive impairment.

Background: The number of people living with dementia is increasing rapidly. Clinical dementia does not develop suddenly, but rather is preceded by a period of cognitive decline beyond normal age-related change. People at this intermediate stage between normal cognitive function and clinical dementia are often described as having mild cognitive impairment (MCI).

Computerised cognitive training for maintaining cognitive function in cognitively healthy people in midlife.

Background: Normal aging is associated with changes in cognitive function that are non-pathological and are not necessarily indicative of future neurocognitive disease. Low cognitive and brain reserve and limited cognitive stimulation are associated with increased risk of dementia. Emerging evidence now suggests that subtle cognitive changes, detectable years before criteria for mild cognitive impairment are met, may be predictive of future dementia.

Computerised cognitive training for maintaining cognitive function in cognitively healthy people in late life.

Background: Increasing age is associated with a natural decline in cognitive function and is also the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or to reduce the risk of dementia is a research priority.

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.

Background: The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine.

Methods: In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study.

Peripheral inflammatory markers in amnestic mild cognitive impairment.

Objective: To prospectively monitor plasma inflammatory marker concentrations in peripheral blood, over 12 months, in subjects with amnestic mild cognitive impairment (MCI), and to determine the relationship between peripheral inflammatory markers and cognitive decline.

Methods: Seventy patients with amnestic MCI were recruited from two sites providing specialist memory assessment services in Manchester. The baseline assessment included physical examination, neuro-psychological testing and venous blood samples for C-reactive protein (CRP) and interleukin 6 (IL-6) concentrations.

The symptomatology of Alzheimer's disease: a cross-cultural study.

Objective: This paper presents the results of a trans-cultural study looking at the possible differences in the symptomatology of Alzheimer's disease (AD) in people from Manchester, UK and Rawalpindi, Pakistan.

Methods: Two groups of people with AD (45 in each group) were recruited at the two sites. The participants and their carers were interviewed to investigate possible differences in demographics and symptomatology including cognition, depression, personality change and every day activities.

The conversational mini-mental state examination: Estimating cognitive impairment.

Formal cognitive testing is an integral part of the mental state examination, and we aimed to test whether clinicians were able to predict the score on the mini-mental state examination (MMSE) by watching a conversation between a person and the interviewer about their memory. A total of 41 professionals rated 30 patients-generally the scores on the MMSE were underestimated and experienced professionals did worse than less experienced practitioners. The results underscore the need for formal cognitive assessment and the requirements for training in the administration of cognitive tests.

Knowledge and attitudes of doctors toward the sexuality of older people in Turkey.

Background: Few studies have looked at healthcare professionals' knowledge of and attitudes to later life sexuality in both Western and Eastern cultures. Here we examine the attitudes and knowledge of Turkish medical doctors toward sexuality in older people.

Method: Eighty-seven doctors, from various specialties, who were directly involved in the care of older people, were contacted by post and asked to complete the Turkish version of the Aging Sexual Knowledge and Attitudes Scale (ASKAS).

Recruitment of consultant psychiatrists from low- and middle-income countries.

The UK's 2-year International Fellowship Programme for consultant doctors has inadvertently highlighted the long-standing issues of the costs and benefits of such recruitment for the countries of origin, and of whether it is ethical for rich countries to recruit health personnel not only from other rich countries but also from low- and middle-income countries. The 'brain drain' from poor to rich countries has been recognised for decades; it occurs in the health sector as well as other sectors, such as education, science and engineering. It has had serious ramifications for the health service infrastructure in low-income countries, where poverty, morbidity, disability and mortality are increasing rather than decreasing, and it is a matter of serious concern for both the World Health Organization and the International Monetary Fund (Carrington & Detragiache, 1998; Lee, 2003).

Pakistan mental health country profile.

The Republic of Pakistan is a South East Asian country with a population of over 140.7 million. Its population is fast growing and the majority (70%) live in rural areas with a feudal or tribal value system.

The biology of psychosis in older people.

The nosology, classification, and biological basis of psychosis in the elderly have been much debated. Psychotic features are seen in schizophrenia, affective illness, and dementia in the elderly. This article reviews evidence for the biological basis of psychosis in older people.