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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.
Systematic review, Meta-Analysis
We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.
RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.
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).
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.
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.
While conducting siderite (FeCO3) solubility experiments in NaCl-Na2CO3 brines, evidence for a second phase was detected. Experiments, in which synthesized siderite was reacted with high ionic strength (0.18 – 7.5 m) solutions at room temperature and high pH (>10), were conducted in a glovebox. As the aging time of siderite-bearing experiments increased, the pH of the solution decreased, signaling formation of a hydroxyl-bearing phase. Decreasing pH values are interpreted to indicate that a hydroxyl-bearing phase, such as chukanovite, is the reaction controlling solid in the solid assemblage. Chukanovite was tentatively identified by XRD analysis. We set out, therefore, to determine the thermodynamic stability of chukanovite under the experimental conditions. Aqueous thermodynamic model parameters were determined with experimentally analyzed Fe(II) solubility data, and subsequently yielded a proposed formation free energy of chukanovite (-1149.8 kJ/mol).
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