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MicroRNAs (miRNAs) modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. Defects in bone homeostasis result in common age-related diseases including osteoporosis. Serum levels of miR-324-3p positively correlate with several features of bone maintenance. In contrast here, using in vivo micro-computed tomography and histology, global miR-324-null mice demonstrated increased bone mineral density and both trabecular and cortical thickness, with effect magnitudes increasing with age. The bone marrow of miR-324-null mice had reduced lipid content while TRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation. Ex vivo assays showed that the high bone mass phenotype of miR-324-null mice resulted from both increased osteoblast activity and decreased osteoclastogenesis. RNA-seq analysis of osteoblasts, osteoclasts and bone marrow macrophages and target validation assays identified that the osteoclast fusion regulator Pin1 and the master osteogenic regulator Runx2 were targets of miR-324-5p in osteoclast lineage cells and osteoblasts, respectively. Indeed, in vitro Runx2 overexpression recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo by the loss of miR-324. Overall, these data demonstrate the importance of miR-324 in bone homeostasis by regulating aspects of both bone formation and remodelling. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dementia is a global health concern with increasing numbers of people living long enough to develop dementia. People with dementia (PwD) may be particularly vulnerable to suicidality. However, suicide in PwD has not been thoroughly explored. The objective of this review was to determine the prevalence and risk factors of suicide in PwD. Five databases were searched from inception to July 2023. Peer-reviewed publications reporting prevalence, risk factors or quantitative summary data for suicide outcomes in PwD were included. Random effects models were used to calculate the pooled prevalence and effect sizes. 54 studies met inclusion criteria. In PwD, the point prevalence of suicidal ideation was 10 % (95 %CI=6 %;16 %), 2-year period prevalence of suicide attempts was 0.8 % (95 %CI=0.3 %;2 %), 10-year period prevalence of suicide attempts was 8.7 % (95 %CI=6.0 %%;12.7 %) and the incidence of death by suicide 0.1 % (95 %CI=0.1 %;0.2 %). Compared to not having dementia, a diagnosis of dementia increased risk of suicidal ideation (OR=1.62[95 %CI=1.17;2.24]) but not risk of suicide attempt (OR=1.77 [95 %CI=0.85;3.69]) or death by suicide (OR=1.30 [95 %CI=0.81;2.10]). People with moderate dementia had significantly increased risk of suicidal ideation than those with mild dementia (OR=1.59[95 %CI=1.11;2.28]), younger PwD were at increased risk of dying by suicide (OR=2.82[95 %CI=2.16;3.68]) and men with dementia were more likely to attempt (OR=1.28[95 %CI=1.25;1.31]) and die by suicide (OR=2.88[95 %CI=1.54;5.39]) than women with dementia. This review emphasises the need for mental health support and suicide prevention in dementia care, emphasising tailored approaches based on age, symptoms, and being male., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To synthesise evidence regarding the association between positive psychological constructs (PPCs) and cognitive function in adults aged 50 +., Methods: Literature searches: Medline, PsycINFO, and Scopus (inception to February 2022). Studies were included if they reported on the association between at least one PPC and one objective measure of cognitive function in people aged 50 + without cognitive impairment at baseline. Where at least two studies reported on the same PPC and cognitive outcome, estimates were pooled through meta-analysis., Findings: In total, 37 studies were included. There was evidence of cross-sectional associations for 'meaning in life' (verbal fluency: b = 0.09, 95 %CI [0.07, 0.11], p < .001; memory: b = 0.10, 95 %CI [0.08, 0.12], p < .001), 'purpose in life' (verbal fluency: b = 0.07, 95 %CI [0.05, 0.08], p < .001; memory: r = 0.13, 95 %CI [0.08, 0.18], p < .001), and positive affect (cognitive state: r = 0.25, 95 %CI [0.14, 0.36], p < .001; memory: r = 0.05, 95 %CI [0.02, 0.08], p < .001) with various domains of cognitive function. However, no significant results were found for life satisfaction (p = .13) or longitudinal studies investigating positive affect and memory (p = .48). Other PPCs were included in narrative syntheses only., Implications: Purpose and meaning in life may be sensible primary targets for interventions to promote healthy cognitive aging. More longitudinal and causal inference research is needed to better understand this association and its implications for clinical practice., Competing Interests: Declaration of Interest We declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To systematically review the literature on outcomes for individuals with subjective cognitive decline (SCD) with concurrent affective symptoms. To conduct a meta-analysis to establish whether either higher depressive symptoms or higher levels of anxiety increased the risk of progression SCD to mild cognitive impairment (MCI) or dementia., Methods: Five databases were searched from inception to February 2021 for longitudinal studies of older adults with SCD, reporting depressive and anxiety symptoms at baseline and risk of MCI or dementia at follow-up. Data were extracted and pooled using a random-effects meta-analysis., Results: Twelve studies were identified. Pooled effect sizes indicated higher depressive symptoms did not increase risk of clinical progression to either MCI (RR = 0.98; 95 % CI: 0.75-1.26) or dementia (RR = 0.69; 95 % CI: 0.27-1.79). However, presence of anxiety or SCD-related worry did significantly increase risk of progression from subjective to objective cognitive impairment by 40 % (RR = 1.40; 95 % CI:1.20 - 1.63)., Conclusions: Affective symptoms in the form of anxiety, but not depressive symptoms, increase the risk of progression to objective cognitive impairment in individuals with SCD. Further research should focus on establishing whether psychological interventions aimed at reducing anxiety and worry also reduce the risk of clinical progression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

It is unclear what non-pharmacological interventions to prevent cognitive decline should comprise. We systematically reviewed lifestyle and psychosocial interventions that aimed to reduce cognitive decline in healthy people aged 50+, and people of any age with Subjective Cognitive Decline or Mild Cognitive Impairment. We narratively synthesised evidence, prioritising results from studies rated as at lower Risk of Bias (ROB) and assigning Centre for Evidence Based Medicine grades. We included 64 papers, describing: psychosocial (n = 12), multi-domain (n = 10), exercise (n = 36), and dietary (n = 6) interventions. We found Grade A evidence that over 4+ months: aerobic exercise twice weekly had a moderate effect on global cognition in people with/ without MCI; and interventions that integrate cognitive and motor challenges (e.g. dance, dumb bell training) had small to moderate effects on memory or global cognition in people with MCI. We found Grade B evidence that 4+ months of creative art or story-telling groups in people with MCI; 6 months of resistance training in people with MCI and a two-year, dietary, exercise, cognitive training and social intervention in people with or without MCI had small, positive effects on global cognition. Effects for some intervention remained up to a year beyond facilitated sessions., (Copyright © 2020. Published by Elsevier B.V.)

Aims: To systematically review longitudinal studies on living alone and incident dementia, to pool the results in a meta-analysis and calculate the population risk., Methods: Embase, Medline and PsycInfo were searched from inception to August 2019 for longitudinal cohort studies of people living alone and risk of dementia. Relative risks (RR) were extracted and effect sizes pooled, with a sensitivity analysis for risk of bias (QUIPS quality rating tool). Population Attributable Fraction (PAF) was calculated, with prevalence of living alone calculated from UK Census data., Results: Twelve studies were identified for inclusion, nine of which had low risk of bias. The pooled effect size indicated an elevated risk of incident dementia when living alone (all studies RR = 1.30; 95 % CI: 1.15-1.46; low risk of bias studies (RR = 1.31; 95 % CI: 1.13-1.51). The PAF for living alone was 8.9 %., Conclusions: Social isolation is a more important risk factor for dementia than previously identified, with living alone associated with greater population risk than physical inactivity, hypertension, diabetes and obesity., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background: Primary cervical dystonia is the most common form of adult-onset focal dystonia. Although most frequently sporadic, 15-20% of patients report a positive family history, suggesting a possible genetic cause. Head tremor is often present in patients with cervical dystonia and may be a prominent symptom., Objective: To describe the clinical characteristics of patients with tremulous cervical dystonia., Methods: Patients with primary cervical dystonia attending our botulinum toxin clinic were assessed with an interview and neurological examination and their notes reviewed. Patients were classified as having either tremulous or non-tremulous cervical dystonia, according to the presence or absence of head tremor on examination. Clinical and demographic data were compared between groups., Results: From 273 patients included (190 females, 83 males), 125 (46%) were classified as tremulous and 148 (54%) as non-tremulous. Tremulous patients were more likely to have a segmental distribution (61% vs. 25%), often involving the arms (48%), and had more frequently associated arm tremor (55% vs. 10%). A positive family history of dystonia and/or tremor was more frequent in tremulous patients (50% vs. 18%)., Conclusions: Patients with cervical dystonia with associated head tremor are more likely to have a segmental distribution (with frequent arm involvement), associated arm tremor and a positive family history, suggesting a genetic etiology in this subgroup of patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)