Supporting the couple relationship following dementia diagnosis: A scoping review.

There is now a significant body of research demonstrating the importance of supporting the couple's relationship for people living with dementia. Maintaining a strong relationship has been demonstrated to slow cognitive decline in dementia, reduce the caregiver's sense of burden and may delay the need for transfer into residential care. However, the potential for healthcare practitioners to deliver interventions to support the couple's relationship in the community remains largely unexplored. This scoping review aimed to locate interventions that support couples to maintain their relationship satisfaction when living with dementia. This review mapped studies across a broad range of disciplines and research methods, following the Joanna Brigg's Institute (JBI) framework. Following screening, 44 studies were identified. The approach of these programmes can be broadly grouped into three categories; Adaptation and use of shared activities to enhance the couple's relationship; Developing caregiver skills and reducing perceived burden to improve interaction and relationship quality; Connecting and strengthening the couple's relationship through sharing feelings and memories. Further research is required to explore the possibility and appropriateness of adaptation of these interventions for use by community healthcare practitioners. There is a need to identify interventions that can meet the needs of couples as dementia progresses into the moderate-severe stages. Heterogeneity and inconsistency in outcomes measurement for the couple's relationship, suggests the need to consider further how outcomes for couple's relationship quality may best be captured. It is also suggested that other existing programmes, outside of the scoping review results, but aimed at reducing dementia caregiver burden may have currently unexplored and developed outcomes for couple's relationship quality

A spatial covariance (123)I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) single photon emission computed tomography to investigate spatial covariance of α4β2 nicotinic acetylcholine receptors in AD and healthy controls. Thirteen AD and 16 controls underwent 1235IA-85380 and regional cerebral blood flow (99mTc-exametazime) single photon emission computed tomography scanning. We applied voxel principal component (PC) analysis, generating series of principal component images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 and regional cerebral blood flow covariance patterns that differentiated AD from controls. The α4β2 pattern showed relative decreased uptake in numerous brain regions implicating several networks including default mode, salience, and Papez hubs. Thus, as well as basal forebrain and brainstem cholinergic system dysfunction, cholinergic deficits mediated through nicotinic acetylcholine receptors could be evident within key networks in AD. These findings may be important for the pathophysiology of AD and its associated cognitive and behavioral phenotypes

Verbal instructions and top-down saccade control

Few studies have addressed the interaction between instruction content and saccadic eye movement control. To assess the impact of instructions on top-down control, we instructed 20 healthy volunteers to deliberately delay saccade triggering, to make inaccurate saccades or to redirect saccades—i.e. to glimpse towards and then immediately opposite to the target. Regular pro- and antisaccade tasks were used for comparison. Bottom-up visual input remained unchanged and was a gap paradigm for all instructions. In the inaccuracy and delay tasks, both latencies and accuracies were detrimentally impaired by either type of instruction and the variability of latency and accuracy was increased. The intersaccadic interval (ISI) required to correct erroneous antisaccades was shorter than the ISI for instructed direction changes in the redirection task. The word-by-word instruction content interferes with top-down saccade control. Top-down control is a time consuming process, which may override bottom-up processing only during a limited time period. It is questionable whether parallel processing is possible in top-down control, since the long ISI for instructed direction changes suggests sequential plannin

The segregated connectome of late-life depression: a combined cortical thickness and structural covariance analysis.

Late-life depression (LLD) has been associated with both generalized and focal neuroanatomical changes including gray matter atrophy and white matter abnormalities. However, previous literature has not been consistent and, in particular, its impact on the topology organization of brain networks remains to be established. In this multimodal study, we first examined cortical thickness, and applied graph theory to investigate structural covariance networks in LLD. Thirty-three subjects with LLD and 25 controls underwent T1-weighted, fluid-attenuated inversion recovery and clinical assessments. Freesurfer was used to perform vertex-wise comparisons of cortical thickness, whereas the Graph Analysis Toolbox (GAT) was implemented to construct and analyze the structural covariance networks. LLD showed a trend of lower thickness in the left insular region (p < 0.001 uncorrected). In addition, the structural network of LLD was characterized by greater segregation, particularly showing higher transitivity (i.e., measure of clustering) and modularity (i.e., tendency for a network to be organized into subnetworks). It was also less robust against random failure and targeted attacks. Despite relative cortical preservation, the topology of the LLD network showed significant changes particularly in segregation. These findings demonstrate the potential for graph theoretical approaches to complement conventional structural imaging analyses and provide novel insights into the heterogeneous etiology and pathogenesis of LLD.This work was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge, PhD studentship.This is the author accepted manuscript. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.neurobiolaging.2016.08.013

Assessment of regional gray matter loss in dementia with Lewy bodies: a surface-based MRI analysis.

OBJECTIVE: To compare magnetic resonance imaging (MRI) patterns of cortical thinning in subjects with dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and normal aging and investigate the relationship between cortical thickness and clinical measures. METHODS: Study participants (31 DLB, 30 AD, and 33 healthy comparison subjects) underwent 3-Tesla T1-weighted MRI and completed clinical and cognitive assessments. We used the FreeSurfer analysis package to measure cortical thickness and investigated the patterns of cortical thinning across groups. RESULTS: Cortical thinning in AD was found predominantly in the temporal and parietal areas extending into the frontal lobes (N = 63, df = 59, t >3.3, p 3.6, p 2.8, p <0.01 uncorrected). CONCLUSION: Cortical thickness may be a sensitive measure for characterising gray matter loss in DLB and highlights important structural imaging differences between the conditions.The study was funded by the Sir Jules Thorn Charitable Trust [grant ref: 05/JTA] and supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the Biomedical Research Centre and Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust.This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S106474811400219X

Cholinergic and perfusion brain networks in Parkinson disease dementia.

OBJECTIVE: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. METHODS: Forty-nine participants (25 PDD and 24 elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). RESULTS: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor-naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. CONCLUSION: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition.Medical Research Council UK [grant number G9817682], and by the National Institute for Health Research (NIHR) Research for Public Benefit, Wellcome Trust (WT088441MA Fellowship funding J-P.T). NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.​1212/​WNL.​000000000000283

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.parkreldis.2016.01.00

Grey matter atrophy in prodromal stage of dementia with Lewy bodies and Alzheimer’s disease

BACKGROUND: Little is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB). METHODS: In this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB (n = 28) and prodromal Alzheimer's disease (pro-AD) (n = 27) and compared and contrasted them with those in elderly control subjects (n = 33) (P ≤ 0.05 corrected for family-wise error). RESULTS: Patients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus. CONCLUSIONS: Atrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.This study was funded by Appel à Projet Interne (API) of the University Hospital of Strasbourg, Alsace Alzheimer 67, Fondation Université de Strasbourg and famille Jean Amrhein, and Projet Hospitalier de Recherche Clinique (PHRC) inter-régional (IDRCB 2012-A00992-41). The work was also supported by the following: the Newcastle Healthcare Charity (BH0070250); Academy of Medical Sciences, Wellcome Trust Starter Grants scheme for Clinical Lecturers (BH090112 to JPT); Wellcome Intermediate Clinical Fellowship (BH083281 to JPT); National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia, based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University; NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge