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Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer’s disease, Alzheimer’s disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis
- Sandeep R. Pagali, Rakesh Kumar, Allison M. LeMahieu, Michael R. Basso, Bradley F. Boeve, Paul E. Croarkin, Jennifer R. Geske, Leslie C. Hassett, John Huston III, Simon Kung, Brian N. Lundstrom, Ronald C. Petersen, Erik K. St. Louis, Kirk M. Welker, Gregory A. Worrell, Alvaro Pascual-Leone, Maria I. Lapid
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- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 08 February 2024, pp. 1-49
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Objective:
We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.
Design:Systematic review, Meta-Analysis
Setting:We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.
Participants and interventions:RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.
Measurement:Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).
Results:The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.
Conclusion:The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.
FC24: Transcranial Magnetic Stimulation (TMS) as a Treatment for Dementia due to non-Alzheimer’s disease (non-AD): What is the Evidence?
- Maria I. Lapid, Sandeep R. Pagali, Rakesh Kumar, Brian N. Lundstrom, Paul E. Croarkin, Simon Kung
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 02 February 2024, pp. 85-86
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Objective:
There is no cure for dementia due to non-Alzheimer’s disease (non-AD), and current treatments are symptomatic. Noninvasive brain stimulation therapies such as transcranial magnetic stimulation (TMS) are increasingly being investigated to improve cognitive function in dementia. We conducted a systematic review to investigate the effectiveness of TMS on cognition in non-AD dementia.
Methods:Comprehensive search of databases (Medline, Embase, Cochrane, APA PsycINFO, Web of Science, and Scopus) from 2000 to February 2023 using keywords related to TMS and dementia (PROSPERO, CRD42022326423). Here we report outcomes from randomized controlled trials (RCTs) of TMS on non-AD dementia populations.
Results:In total, 20 RCTs comprised of 660 patients, mean age 62 years (range 46-71). Diagnostic groups include stroke (n=8), Parkinson’s disease (n=6), Frontotemporal dementia (n=3), Huntington’s disease (n=2) and Progressive non-fluent aphasia (n=1). The most common site of stimulation was left (L) dorsolateral prefrontal cortex (DLPFC, n=13); other sites were primary motor cortex (n=2); Right (R) Broca's area, Brodmann area, Contralesional pars triangularis, R Inferior Frontal Gyrus (IFG) (all n=1); and multiple sites in 1 RCT (L and R IFG, L superior frontal gyrus, L DLPFC, L and R right anterior temporal lobe, supplementary motor area, anterior cingulate, and vertex). Studies used both low (1Hz, n=5) and high (50Hz, n=5) frequencies, or other high (5Hz, 10Hz, 20Hz) or combination low/high frequencies. Frequent duration of treatment was 10 days (n=7), range 1-40. Of 20 studies, 19 (95%) demonstrated improvement of global cognition (on MoCA, MMSE) and specific cognitive domains (learning and memory, language, executive function, problem-solving, attention, reaction time). The only RCT with no effect utilized a single session intermittent theta burst stimulation on the LDLPFC on PD patients. Adverse events in 7 studies included headaches (most common), dull skull pain, dizziness, insomnia, fatigue, anxiety, temporary decrease in hearing, and temporary decreased mental clarity.
Conclusion:There is favorable evidence that rTMS improves global and specific cognitive domains in non-AD dementia. Left DLPFC is the most common stimulation site, both low- and high-frequency are utilized, and 10 sessions is frequently used. Further studies are needed to determine optimal TMS treatments in cognitively impaired populations
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Pharmacologic interventions for antidepressant-induced sexual dysfunction: a systematic review and network meta-analysis of trials using the Arizona sexual experience scale
- Marissa J. Luft, Eric T. Dobson, Amir Levine, Paul E. Croarkin, Jeffrey R. Strawn
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- Journal:
- CNS Spectrums / Volume 27 / Issue 4 / August 2022
- Published online by Cambridge University Press:
- 12 April 2021, pp. 496-505
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Background
Despite the prevalence of antidepressant-related sexual side effects, comparisons of treatments for these problematic side effects are lacking.
MethodsTo address this, we performed a systematic review and Bayesian network meta-analysis to compare interventions for antidepressant-induced sexual dysfunction in adults. Using PubMed and clinicaltrials.gov, we identified published and unpublished prospective treatment trials from 1985 to September 2020 (primary outcome: the Arizona sexual experience scale [ASEX] score). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.
ResultsWe identified 57 citations (27 randomized controlled trials, 66 treatment arms, 27 open-label trials, and 3 crossover trials) that evaluated 33 interventions (3108 patients). In the systematic review, 44% (25/57) of trials reported successful interventions; this was more common in open-label (70%, 19/27) compared to placebo-controlled studies (22%, 6/27). In the meta-analysis of placebo-controlled studies that used the ASEX (N = 8), pycnogenol was superior to placebo (standardized mean difference: −1.8, 95% credible interval [CrI]: [−3.7 to 0.0]) and there was evidence that, at a 6% threshold, sildenafil improved sexual dysfunction (standardized mean difference: −1.2, 95% CrI [−2.5 to 0.1]). In the meta-analysis including single-arm studies (15 studies), treatment response was more common with sildenafil, tianeptine, maca, tiagabine, and mirtazapine compared to placebo, but these differences failed to reach statistical significance.
ConclusionsWhile heterogeneity across randomized controlled trials complicates identifying the single best intervention, multiple trials suggest that sildenafil ameliorates antidepressant-induced sexual dysfunction. More randomized controlled trials are needed to examine the putative efficacy of other interventions.
Suicidality and self-injurious behavior among adolescent social media users at psychiatric hospitalization
- Reem M.A. Shafi, Paul A. Nakonezny, Magdalena Romanowicz, Aiswarya L. Nandakumar, Laura Suarez, Paul E. Croarkin
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- Journal:
- CNS Spectrums / Volume 26 / Issue 3 / June 2021
- Published online by Cambridge University Press:
- 27 April 2020, pp. 275-281
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Background
The current study sought to examine the relationship between documented social media use and suicidality and self-injurious behaviors in adolescents at the time of psychiatric hospitalization.
MethodsWe retrospectively identified adolescents (aged 12-17 years) hospitalized on an inpatient psychiatric unit during 1 year. Abstracted information included documented social media use, demographic variables, documented self-injurious behaviors, the Patient Health Questionnaire-9, and the Suicide Status Form-II. Logistic regression was implemented to examine the effect of social media use on the risk of self-injurious behaviors and suicidality.
ResultsFifty-six adolescents who used social media were identified and matched with 56 non-social media users. Those with reported social media use had significantly greater odds of self-injurious behaviors at admission (odds ratio, 2.55; 95% confidence intervals, 1.17-5.71; P = .02) vs youth without reported social media use. Adolescents with reported social media use also had greater odds of increased suicidal ideation and suicide risk than those with no reported use, but these relationships were not statistically significant.
ConclusionsSocial media use in adolescents with a psychiatric admission may be associated with the risk of self-injurious behaviors and could be a marker of impulsivity. Further work should guide the assessment of social media use as part of a routine adolescent psychiatric history.