Trajectories and Determinants of Quality of Life in Dementia with Lewy Bodies and Alzheimer's Disease

Background: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking. Objective: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer’s disease (AD) and controls. Methods: QoL was assessed annually in 138 individuals, using the EQ5D-utility-score (0–100) and the health-related Visual Analogue Scale (VAS, 0–100). Twenty-nine DLB patients (age 69 ± 6), 68 AD patients (age 70 ± 6), and 41 controls (age 70 ± 5) were selected from the Dutch Parelsnoer Institute-Neurodegenerative diseases and Amsterdam Dementia Cohort. We examined clinical work-up over time as determinants of QoL, including cognitive tests, neuropsychiatric inventory, Geriatric Depression Scale (GDS), and disability assessment of dementia (DAD). Results: Mixed models showed lower baseline VAS-scores in DLB compared to AD and controls (AD: ±SE = -7.6 ± 2.8, controls: ±SE = -7.9 ± 3.0, p < 0.05). An interaction between diagnosis and time since diagnosis indicated steeper decline on VAS-scores for AD patients compared to DLB patients (±SE = 2.9 ± 1.5, p < 0.1). EQ5D-utility-scores over time did not differ between groups. Higher GDS and lower DAD-scores were independently associated with lower QoL in dementia patients (GDS: VAS ±SE = -1.8 ± 0.3, EQ5D-utility ±SE = -3.7 ± 0.4; DAD: VAS = 0.1 ± 0.0, EQ5D-utility ±SE = 0.1 ± 0.1, p < 0.05). No associations between cognitive tests and QoL remained in the multivariate model. Conclusion: QoL is lower in DLB, while in AD QoL shows steepe

Sex differences in brain atrophy in dementia with Lewy bodies

\ua9 2023 The Authors. Alzheimer\u27s &amp; Dementia published by Wiley Periodicals LLC on behalf of Alzheimer\u27s Association.INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 \ub1 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 \ub1 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age

Multimodal behavioral treatment of migraine: An Internet-administered, randomized, controlled trial

Introduction. Multimodal approaches in behavioral treatment have gained recent interest, with proven efficacy for migraine. The utility of the Internet has been demonstrated for behavioral treatment of headache disorders, but not specifically for migraine. The aim of the study was to develop and evaluate an Internet-based multimodal behavior treatment (MBT) program for migraine and to test hand massage treatment as an adjunct. Methods. Eighty-three adults, 58 women and 25 men, with at least two migraine attacks a month were recruited via advertisements. An MBT program aiming at improvements in life-style and stress coping was developed for this study and, together with a diary, adapted for use over the Internet. Participants were randomized to MBT with and without hand massage and to a control group, and were followed for 11 months. Questionnaires addressing issues of quality of life (PQ23) and depressive symptoms (MADRS-S) were used. Results. A 50%, or greater, reduction in migraine frequency was found in 40% and 42% of participants of the two groups receiving MBT (with and without hand massage, respectively), who statistically were significantly more improved than participants in the control group. No effect of hand massage was detected, and gender did not show any independent contribution to the effect in a multivariate analysis. Conclusions. MBT administered over the Internet appears feasible and effective in the treatment of migraine, but no effect of hand massage was found. For increased knowledge on long-term effects and the modes of action of the present MBT program, further studies are needed

The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer's dementia

Since Alzheimer’s disease may affect driving performance, patients with Alzheimer’s disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer’s disease will pass or fail an on-road driving assessment. Patients with Alzheimer’s disease (n = 81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811–819, 2017]. All patients with Alzheimer’s disease who scored below the lower cutoff (MMSE ≤ 19) failed the on-road driving assessment. However, a third of the patients with Alzheimer’s disease who scored above the upper cutoff (MMSE ≥ 25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer’s disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting

Limited Value of Staging Squamous Cell Carcinoma of the Anal Margin and Canal Using the Sentinel Lymph Node Procedure: A Prospective Study with Long-Term Follow-Up

Background. Selection of patients with anal cancer for groin irradiation is based on tumor size, palpation, ultrasound, and fine needle cytology. Current staging of anal cancer may result in undertreatment in small tumors and overtreatment of large tumors. This study reports the feasibility of the sentinel lymph node biopsy (SLNB) in patients with anal cancer and whether this improves the selection for inguinal radiotherapy. Methods. A total of 50 patients with squamous anal cancer were evaluated prospectively. Patients without a SLNB (n = 29) received irradiation of the inguinal lymph nodes based on lymph node status, tumor size, and location of the primary tumor. Inguinal irradiation treatment in patients with a SLNB was based on the presence of metastases in the SLN. Results. SLNs were found in all 21 patients who underwent a SLNB. There were 5 patients (24%) who had complications after SLNB and 7 patients (33%) who had a positive SLN and received inguinal irradiation. However, 2 patients with a tumor-free SLN and no inguinal irradiation developed lymph node metastases after 12 and 24 months, respectively. Conclusions. We conclude that SLNB in anal cancer is technically feasible. SLNB can identify those patients who would benefit from refrain of inguinal irradiation treatment and thereby reducing the incidence of unnecessary inguinal radiotherapy. However, because of the occurrence of inguinal lymph node metastases after a tumor-negative SLNB, introduction of this procedure as standard of care in all patients with anal carcinoma should be done with caution to avoid undertreatment of patient who otherwise would benefit from inguinal radiotherapy

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

This is the final version of the article. Available from the publisher via the DOI in this record.Open Access funded by Wellcome TrustThe similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.Rita Guerreiro and Jose Bras are supported by Research Fellowships from the Alzheimer's Society. This work was supported in part by a Parkinson's UK Innovation Award (K-1204) in collaboration with the Lewy Body Society and by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium whose members are from the UCL Institute of Neurology, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee and by an anonymous Foundation. The authors would like to acknowledge Elena Lorenzo for her technical assistance. This study was supported in part by grants from the Spanish Ministry of Science and InnovationSAF2006-10126 (2006–2009) and SAF2010-22329-C02-01 (2011–2013) and SAF2013-47939-R (2013–2015) to Pau Pastor and by the UTE project FIMA to Pau Pastor. They acknowledge the Oxford Brain Bank, supported by the Medical Research Council (MRC), Brains for Dementia Research (BDR) (Alzheimer Society and Alzheimer Research UK), Autistica UK, and the NIHR Oxford Biomedical Research Centre. The sample collection and database of the Amsterdam Dementia Cohort was funded by Stichting Dioraphte and Stichting VUMC fonds. Glenda M. Halliday is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia. For the neuropathologically confirmed samples from Australia, brain tissue was received from the Sydney Brain Bank, which is supported by Neuroscience Research Australia, the University of New South Wales, and the National Health and Medical Research Council of Australia. This study was also partially funded by the Wellcome Trust, Medical Research Council, Canadian Institutes of Health Research, Ontario Research Fund. The Nottingham Genetics Group is supported by ARUK and The Big Lottery Fund. The effort from Columbia University was supported by the Taub Institute, the Panasci Fund, the Parkinson's Disease Foundation, and NIH grants NS060113 (Lorraine Clark), P50AG008702 (P.I. Scott Small), P50NS038370 (P.I. R. Burke), and UL1TR000040 (P.I. H. Ginsberg). Owen A. Ross is supported by the Michael J. Fox Foundation, NINDS R01# NS078086. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS072187) and is supported by the Mangurian Foundation for Lewy body research. This work has received support from The Queen Square Brain Bank at the UCL Institute of Neurology. Some of the tissue samples studies were provided by the MRC London Neurodegenerative Diseases Brain Bank and the Brains for Dementia Research project (funded by Alzheimer's Society and ARUK). This research was supported in part by the NIHR UCLH Biomedical Research Centre, the Queen Square Dementia Biomedical Research Unit, the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College Hospital, London. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project AG000951-12. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust and the Medical Research Council

Exome sequencing identifies novel AD-associated genes

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD