Parental Age and the Risk for Alzheimer’s Disease in Offspring: Systematic Review and Meta-Analysis

Background: Alzheimer’s disease (AD) is the most common cause of dementia worldwide, accounting for 50–75% of all cases. While older maternal and paternal age at childbirth are established risk factors for Down syndrome which is associated with later AD, it is still not entirely clear whether parental age is a risk factor for AD. Previous studies have suggested contradictory findings. Objectives: We conducted a systematic review and meta-analysis to examine whether parental (maternal and paternal) age at birth was associated with AD and whether individuals born to younger or older parents were at an increased risk for AD. Methods: Two reviewers searched the electronic database of PubMed for relevant studies. Eligibility for the meta-analysis was based on the following criteria: (1) studies involving patients with AD and an adequate control group, (2) case control or cohort studies, (3) studies investigating parental age. All statistical analyses were completed in STATA/IC version 16. Results: Eleven studies involving 4,371 participants were included in the systematic review and meta-analysis. Meta-analysis demonstrated no significant association between maternal (weighted mean difference [WMD] 0.49, 95% CI –0.52 to 1.49, p = 0.34) and paternal age and AD (WMD 1.00, 95% CI –0.55 to 2.56, p = 0.21). Similarly, individuals born to younger (<25 years) or older parents (>35 years) did not demonstrate a differential risk for AD. Conclusions: Overall, this meta-analysis did not demonstrate an association between parental age and the risk of AD in offspring. These findings should be interpreted with caution given the limited power of the overall meta-analysis and the methodological limitations of the underlying studies as in many cases no adjustment for potential confounders was included

The genomics of visuospatial neurocognition in obsessive-compulsive disorder: A preliminary GWAS

© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).[Background] The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex traits such as OCD.[Methods] We analyzed the association of SNPs across the whole genome with the construction of visuospatial information and executive performance through four neurocognitive variables assessed by the Rey-Osterrieth Complex Figure Test (ROCFT) in a sample of 133 OCD probands. Analyses were performed at SNP- and gene-level.[Results] No SNP reached genome-wide significance, although there was one SNP almost reaching significant association with copy organization (rs60360940; P = 9.98E-08). Suggestive signals were found for the four variables at both SNP- (P < 1E-05) and gene-levels (P < 1E-04). Most of the suggestive signals pointed to genes and genomic regions previously associated with neurological function and neuropsychological traits.[Limitations] Our main limitations were the sample size, which was limited to identify associated signals at a genome-wide level, and the composition of the sample, more representative of rather severe OCD cases than a population-based OCD sample with a broad severity spectrum.[Conclusions] Our results suggest that studying neurocognitive variables in GWAS would be more informative on the genetic basis of OCD than the classical case/control GWAS, facilitating the genetic characterization of OCD and its different clinical profiles, the development of individualized treatment approaches, and the improvement of prognosis and treatment response.This work was supported by Carlos III Health Institute (PI16/00950, PI16/00950, PI22/00752); FEDER funds (‘A way to build Europe’), and CERCA Programme / Generalitat de Catalunya. MA was supported by a Juan de la Cierva contract (FJC2021-047538-I).Peer reviewe

Vocal Culture in the Age of Laryngoscopy

For several months beginning in 1884, readers of Life, Science, Health, the Atlantic Monthly and similar magazines would have encountered half-page advertisements for a newly patented medical device called the ‘ammoniaphone’ (Figure 2.1). Invented and promoted by a Scottish doctor named Carter Moffat and endorsed by the soprano Adelina Patti, British Prime Minister William Gladstone and the Princess of Wales, the ammoniaphone promised a miraculous transformation in the voices of its users. It was recommended for ‘vocalists, clergymen, public speakers, parliamentary men, readers, reciters, lecturers, leaders of psalmody, schoolmasters, amateurs, church choirs, barristers, and all persons who have to use their voices professionally, or who desire to greatly improve their speaking or singing tones’. Some estimates indicated that Moffat sold upwards of 30,000 units, yet the ammoniaphone was a flash in the pan as far as such things go, fading from public view after 1886

Science, Technology and Love in Late Eighteenth-Century Opera

It is a tale told by countless operas: young love, thwarted by an old man’s financially motivated marriage plans, triumphs in the end thanks to a deception that tricks the old man into blessing the young lovers’ union. Always a doddering fool, the old man is often also an enthusiast for knowledge. Such is the case, for instance, in Carlo Goldoni’s comic opera libretto Il mondo della luna (1750), in which Buonafede’s interest in the moon opens him to an elaborate hoax that has him believe he and his daughters have left Earth for the lunar world; and also in the Singspiel Die Luftbälle, oder der Liebhaber à la Montgolfier (1788), wherein the apothecary Wurm trades Sophie, the ward he intended to marry himself, for a technological innovation that will make him a pioneering aeronaut

Opera and Hypnosis: Victor Maurel’s Experiments with Verdi’s Otello

One day in his private home on the avenue Bugeaud, in Paris’s sixteenth arrondissement, the famous baritone Victor Maurel hosted a meeting which combined music with hypnotism of a young woman

Operatic Fantasies in Early Nineteenth-Century Psychiatry

In his celebrated essay on insanity in the Dictionnaire des sciences médicales (1816), French psychiatrist Étienne Esquirol marvelled at the earlier custom of allowing asylum inmates to attend theatrical productions at Charenton

Unsound Seeds

With this image of a curtain hiding and at the same time heightening some terrible secret, Max Kalbeck began his review of the first Viennese performance of Richard Strauss’s Salome. Theodor W. Adorno picked up the image of the curtain in the context of Strauss’s fabled skill at composing non-musical events, when he identified the opening flourish of Strauss’s Salome as the swooshing sound of the rising curtain. If this is so, the succès de scandale of the opera was achieved, in more than one sense, as soon as the curtain rose at Dresden’s Semperoper on 10 December 1905. Critics of the premiere noted that the opera set ‘boundless wildness and degeneration to music’; it brought ‘high decadence’ onto the operatic stage; a ‘composition of hysteria’, reflecting the ‘disease of our time’, Salome is ‘hardly music any more’.The outrage did not end there

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome

Introduction: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients.Material and methods: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: (‘Tourette syndrome’ [MeSH Terms] OR ‘Gilles de la Tourette syndrome’ [MeSH Terms] OR ‘tic disorders’ [MeSH Terms] OR ‘tics’ [MeSH Terms] OR ‘tic disorders’[Title/Abstract]) AND (‘cannabis-based medicine’ [Title/Abstract] OR ‘cannabis’ [Title/Abstract] OR ‘dronabinol’ [Title/Abstract] OR ‘nabiximols’ [Title/Abstract] OR ‘tetrahydrocannabinol’ [Title/Abstract] OR ‘THC’ [Title/Abstract] OR ‘cannabidiol’ [Title/Abstract], limit: ‘humans’. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV).Results: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant.Conclusions: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS

The effects of stimulant dose and dosing strategy on treatment outcomes in attention-deficit/hyperactivity disorder in children and adolescents: a meta-analysis

Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose–response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose–response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.</p