Systems modeling of white matter microstructural abnormalities in Alzheimer's disease

INTRODUCTION: Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD). However, it is unclear which brain regions have the strongest WM changes in presymptomatic AD and what biological processes underlie WM abnormality during disease progression. METHODS: We developed a systems biology framework to integrate matched diffusion tensor imaging (DTI), genetic and transcriptomic data to investigate regional vulnerability to AD and identify genetic risk factors and gene subnetworks underlying WM abnormality in AD. RESULTS: We quantified regional WM abnormality and identified most vulnerable brain regions. A SNP rs2203712 in CELF1 was most significantly associated with several DTI-derived features in the hippocampus, the top ranked brain region. An immune response gene subnetwork in the blood was most correlated with DTI features across all the brain regions. DISCUSSION: Incorporation of image analysis with gene network analysis enhances our understanding of disease progression and facilitates identification of novel therapeutic strategies for AD

Executive functions in the elderly with Mild Cognitive Impairment: a systematic review on motor and cognitive inhibition, conflict control and cognitive flexibility

Background: Mild Cognitive Impairment (MCI) is a syndrome characterised by mild cognitive decline, on one or more domains, but which does not compromise daily functions. Several studies have investigated the relationship between MCI and deficit in executive functions (EFs) but, unlike robust evidence in the mnestic domain, the nature of executive deficits in the MCI population remains uncertain. Objectives: This systematic review aims to evaluate EFs in patients with MCI, considering inhibition (motor and cognitive), conflict control and cognitive flexibility. Method: The databases used for the search were PUBMED, PsycINFO, PsycARTICLES and MEDLINE. Eligibility criteria: use of specific paradigms for EFs assessment ("Wisconsin Card Sorting Test", "Stroop Task", "Go/No-Go Task", "Flanker Task"); age over 65, studies published in English. Exclusion criteria: presence of dementia; psychiatric disorders; stroke; cranial trauma; inclusion of participants with MCI in groups with healthy elderly or those with dementia. Results: Fifty-five studies were selected, namely: Stroop Task (N=30), WCST (N=14), Go/No-Go (N=9), Flanker Task (N=2). Results have shown in people with MCI deficits in all the EFs considered. Conclusions: The results of this review support the applicability of the four experimental tasks examined for the study of EFs in people with MCI. These paradigms are useful in research, diagnosis and therapeutic purposes, allowing obtaining an articulated EFs profile that can compromise the daily life in elderly. These EFs are not generally evaluated by standard assessment of MCI, but their evaluation can lead to a better knowledge of MCI and help in the diagnosis and treatment

Role of Artificial Intelligence (AI) art in care of ageing society: focus on dementia

open access articleBackground: Art enhances both physical and mental health wellbeing. The health benefits include reduction in blood pressure, heart rate, pain perception and briefer inpatient stays, as well as improvement of communication skills and self-esteem. In addition to these, people living with dementia benefit from reduction of their noncognitive, behavioural changes, enhancement of their cognitive capacities and being socially active. Methods: The current study represents a narrative general literature review on available studies and knowledge about contribution of Artificial Intelligence (AI) in creative arts. Results: We review AI visual arts technologies, and their potential for use among people with dementia and care, drawing on similar experiences to date from traditional art in dementia care. Conclusion: The virtual reality, installations and the psychedelic properties of the AI created art provide a new venue for more detailed research about its therapeutic use in dementia

Development of the CHARIOT Research Register for the Prevention of Alzheimer’s Dementia and Other Late Onset Neurodegenerative Diseases

Identifying cognitively healthy people at high risk of developing dementia is an ever-increasing focus. These individuals are essential for inclusion in observational studies into the natural history of the prodromal and early disease stages and for interventional studies aimed at prevention or disease modification. The success of this research is dependent on having access to a well characterised, representative and sufficiently large population of individuals. Access to such a population remains challenging as clinical research has, historically, focussed on patients with dementia referred to secondary and tertiary services. The primary care system in the United Kingdom allows access to a true prodromal population prior to symptoms emerging and specialist referral. We report the development and recruitment rates of the CHARIOT register, a primary care-based recruitment register for research into the prevention of dementia. The CHARIOT register was designed specifically to support recruitment into observational natural history studies of pre-symptomatic or prodromal dementia stages, and primary or secondary prevention pharmaceutical trials or other prevention strategies for dementia and other cognitive problems associated with ageing.Participants were recruited through searches of general practice lists across the west and central London regions. Invitations were posted to individuals aged between 60 and 85 years, without a diagnosis of dementia. Upon consent, a minimum data set of demographic and contact details was extracted from the patient's electronic health record.To date, 123 surgeries participated in the register, recruiting a total of 24,509 participants-a response rate of 22.3%. The age, gender and ethnicity profiles of participants closely match that of the overall eligible population. Higher response rates tended to be associated with larger practices (r = 0.34), practices with a larger older population (r = 0.27), less socioeconomically disadvantaged practices (r = 0.68), and practices with a higher proportion of White patients (r = 0.82).Response rates are comparable to other registers reported in the literature, and indicate good interest and support for a research register and for participation in research for the prevention of age-related neurodegenerative diseases and dementia. We consider that the simplicity of the approach means that this system is easily scalable and replicable across the UK and internationally

Optical coherence tomography in Alzheimer's disease. A meta-analysis

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies. METHODS AND FINDINGS: Data sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls. RESULTS: 11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in μm, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06). CONCLUSION: Results from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments