21 research outputs found
Serum 25-hydroxyvitamin D and cognitive decline in the very old: The Newcastle 85+ study
No full textBackground and purpose:
Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.
Methods:
Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles.
Results:
Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06–2.60, P = 0.03; 1.62, 95% confidence interval 1.02–2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, b = 0.023, P = 0.01; highest, b = 0.021, P = 0.02), Digit Vigilance Task (lowest, b = 0.009, P = 0.05; highest,b = 0.01, P = 0.02) and Power of Attention (lowest, b = 0.017, P = 0.02;highest, b = 0.022, P = 0.002) and greater Reaction Time Variability (lowest,b = 0.021, P = 0.02; highest, b = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication.
Conclusion:
Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment
Non-clinical hallucinations and mental imagery across sensory modalities
No full text\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Introduction: Vivid mental imagery has been proposed to increase the likelihood of experiencing hallucinations. Typically, studies have employed a modality general approach to mental imagery which compares imagery across multiple domains (e.g., visual, auditory and tactile) to hallucinations in multiple senses. However, modality specific imagery may be a better predictor of hallucinations in the same domain. The study examined the contribution of imagery to hallucinations in a non-clinical sample and specifically whether imagery best predicted hallucinations at a modality general or modality specific level. Methods: In study one, modality general and modality specific accounts of the imagery-hallucination relationship were contrasted through application of self-report measures in a sample of 434 students. Study two used a subsample (n = 103) to extend exploration of the imagery-hallucinations relationship using a performance-based imagery task. Results: A small to moderate modality general relationship was observed between self-report imagery and hallucination proneness. There was only evidence of a modality specific relationship in the tactile domain. Performance-based imagery measures were unrelated to hallucinations and self-report imagery. Conclusions: Mental imagery may act as a modality general process increasing hallucination proneness. The observed distinction between self-report and performance-based imagery highlights the difficulty of accurately measuring internal processes
Estimating the severity of intellectual disability in adults: A Mokken scaling analysis of the Learning Disability Screening Questionnaire.
No full textA Mokken scaling analysis of the learning disability screening questionnaire (LDSQ) suggested that, with the exception of 1 item, the scale conforms to the properties of a Mokken scale. This has advantages for estimating the severity of intellectual disability and inferring the difficulties likely to be experienced by an individual for whom there is incomplete information on intellectual and adaptive functioning
Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort.
No full textCross-sectional studies reported associations between short leucocyte telomere length (LTL) and measures of vascular and cardiac damage. However, the contribution of LTL dynamics to the age-related process of cardiovascular (CV) remodelling remains unknown. In this study, we explored whether the rate of LTL shortening can predict CV phenotypes over 10-year follow-up and the influence of established CV risk factors on this relationship
A Review of Multimodal Hallucinations: Categorization, Assessment, Theoretical Perspectives, and Clinical Recommendations
No full text\ua9 The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Hallucinations can occur in different sensory modalities, both simultaneously and serially in time. They have typically been studied in clinical populations as phenomena occurring in a single sensory modality. Hallucinatory experiences occurring in multiple sensory systems-multimodal hallucinations (MMHs)-are more prevalent than previously thought and may have greater adverse impact than unimodal ones, but they remain relatively underresearched. Here, we review and discuss: (1) the definition and categorization of both serial and simultaneous MMHs, (2) available assessment tools and how they can be improved, and (3) the explanatory power that current hallucination theories have for MMHs. Overall, we suggest that current models need to be updated or developed to account for MMHs and to inform research into the underlying processes of such hallucinatory phenomena. We make recommendations for future research and for clinical practice, including the need for service user involvement and for better assessment tools that can reliably measure MMHs and distinguish them from other related phenomena
Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases
No full text\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.BACKGROUND AND HYPOTHESIS: Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; eg, Parkinson\u27s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; eg, psilocybin and mescaline). While these conditions differ in etiology, overlapping phenomenology, and neural mechanisms suggest shared pathways. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation. STUDY DESIGN: This narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology. STUDY RESULTS: Both LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Some features in LBDs resemble those induced by SPs (eg, illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT2AR and 5-HT1AR) modulation, while in LBDs, 5-HT2A receptor upregulation correlates with increased VH, and its inhibition (eg, with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation. CONCLUSIONS: Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between sensory degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations
Hallucinations in Older Adults: A Practical Review
No full text\ua9 The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.Older adults experience hallucinations in a variety of social, physical, and mental health contexts. Not everyone is open about these experiences, as hallucinations are surrounded with stigma. Hence, hallucinatory experiences in older individuals are often under-recognized. They are also commonly misunderstood by service providers, suggesting that there is significant scope for improvement in the training and practice of professionals working with this age group. The aim of the present article is to increase knowledge about hallucinations in older adults and provide a practical resource for the health and aged-care workforce. Specifically, we provide a concise narrative review and critique of (1) workforce competency and training issues, (2) assessment tools, and (3) current treatments and management guidelines. We conclude with a brief summary including suggestions for service and training providers and future research
Histamine H3 Receptor Heterogeneity in the Central Nervous System in Aging and Dementia.
No full textAbstract
The histamine H3R is a classic G-protein coupled receptor and is a potential therapeutic target for a number of central nervous system pathologies. Major pharmacological heterogeneity between and within species has hindered the clinical development of H3R-targeted drugs. The pharmacological heterogeneity displayed by the H3R is thought in part to be a result of alternative splicing of the H3R which generates a number of possible splice variants, some of which have been shown to be functional and others which appear to be non-functional in terms of ligand binding and signal transduction. mRNA encoding the different isoforms has been shown to be distributed throughout the central nervous system in a region specific manner. For the first time we have shown three of the common H3R isoforms (hH3 329, hH3 365, hH3 445) to be expressed in the human brain using a novel panel of immunological isoform specific probes. We provide preliminary evidence for raised levels of H3 445 and H3 329 isoforms in Parkinson’s disease and Lewy Body Dementia cases, respectively, compared to age-matched controls. We have shown a variety of H3R ligands display differential pharmacological properties at the three hH3R isoforms expressed in HEK 293 cells. Most notably a 5- and 10- fold lower affinity for a highly selective clinical lead H3R inverse antagonist, GSK189254, at the H3R 329 and H3R 329 + 365 isoforms, respectively. The pharmacological differences observed indicate, together with the availability of the immunological probes, that it will be possible to dissect the physiological roles of human H3 receptor isoforms.
The H3R is an attractive therapeutic target for age-related dementias. H3R antagonists have undergone a large number of pre-clinical assessments in which they display pro-cognitive effects, particularly in drug-induced amnesias. It is important to establish whether there are any changes in H3R expression in normal physiological aging and in age-related human dementias. Based on quantitative [3H] GSK189254 autoradiography, we have shown that H3Rs are largely preserved in key cortical and striatal brain regions in aged CD-1 and TASPM mice, as well as in aged humans. Furthermore, H3 receptors were largely unchanged in Lewy Body Dementia and Alzheimer’s disease cases, which provide further evidence validating the H3R as a promising target for age-related cognitive disorders. Psychotic symptoms are common features in both Lewy Body Dementia and Alzheimer’s disease. Interestingly, higher levels of H3R in the globus pallidus correlated with the presence of both delusions (+ 40% and + 37%) and hallucination symptoms (+22% and +14%) within these human dementias, consistent with the recent positive clinical use of H3R antagonists in psychotic disorders. In contrast, using a novel validated all-in-one behavioural elevated platform test in mice, evidence is provided for the lack of H3R involvement in anxiety behaviour, suggesting the lack of utility in human anxiety disorders
Serum thyroid function, mortality and disability in advanced old age: The newcastle 85+ study
No full textContext: Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood. Objective: This study sought to determine whether thyroidhormonestatusandvariation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds. Design: A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years. Setting and Participants: Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom. Main Outcomes: All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count. Results: After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P < .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively. Conclusions: Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serumTSHlevels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges
Visual hallucinations in neurological and ophthalmological disease: Pathophysiology and management
No full text\ua9 2020 Author(s) (or their employer(s)). Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson\u27s disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson\u27s disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop. Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations
