Cholinesterase inhibitors and falls, syncope and injuries in patients with cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Cholinesterase inhibitors are commonly used to treat patients with neurocognitive disorders, who often have an elevated risk of falling. Effective use of these medications requires a thoughtful assessment of risks and benefits. OBJECTIVE: To provide an update on previous reviews and determine the association between cholinesterase inhibitors and falls, syncope, fracture and accidental injuries in patients with neurocognitive disorders. METHODS: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature and AgeLine were systematically searched through March 2023 to identify all randomised controlled trials of cholinesterase inhibitors (donepezil, galantamine, rivastigmine) in patients with cognitive impairment. Corresponding authors were contacted for additional data necessary for meta-analysis. Inclusion criteria consisted of adults ≥19 years, with a diagnosis of dementia, Parkinson's disease, mild cognitive impairment or traumatic brain injury. Data were extracted in duplicate for the aforementioned primary outcomes and all outcomes were analysed using random-effects meta-analysis. RESULTS: Fifty three studies (30 donepezil, 14 galantamine, 9 rivastigmine) were included providing data on 25, 399 patients. Cholinesterase inhibitors, compared to placebo, were associated with reduced risk of falls (risk ratio [RR] 0.84 [95% confidence interval [CI] = 0.73-0.96, P = 0.009]) and increased risk of syncope (RR 1.50 [95% CI = 1.02-2.21, P = 0.04]). There was no association with accidental injuries or fractures. CONCLUSION: In patients with neurocognitive disorders, cholinesterase inhibitors were associated with decreased risk of falls, increased risk of syncope and no association with accidental trauma or fractures. These findings will help clinicians better evaluate risks and benefits of cholinesterase inhibitors.

Impact of a Carbohydrate Mouth Rinse on Corticomotor Excitability after Mental Fatigue in Healthy College-Aged Subjects.

Mental Fatigue (MF) has been associated with reduced physical performance but the mechanisms underlying this result are unclear. A reduction in excitability of the corticomotor system is a way mental fatigue could negatively impact physical performance. Carbohydrate (CHO) mouth rinse (MR) has been shown to increase corticomotor excitability. PURPOSE: The purpose of this study was to determine if CHO MR impacts corticomotor excitability after MF. METHODS: Fifteen subjects (nine females, six males; age = 23 ± 1 years; height = 171 ± 2 cm; body mass = 69 ± 3 kg; BMI = 23.8 ± 0.7) completed two sessions under different MR conditions (Placebo (PLAC), 6.4% glucose (CHO)) separated by at least 48 h and applied in a double-blinded randomized fashion. Motor-evoked potential (MEP) of the left first dorsal interosseous (FDI) was determined by transcranial magnetic stimulation (TMS) before and after MF. Perceived MF was recorded before and after the MF task using a 100 mm visual analog scale (VAS). RESULTS: MF was greater following PLAC (+30.4 ± 4.0 mm) than CHO (+19.4 ± 3.9 mm) (p = 0.005). MEP was reduced more following PLAC (-16.6 ± 4.4%) than CHO (-3.7 ± 4.7%) (p < 0.001). CONCLUSIONS: CHO MR was successful at attenuating the reduction in corticomotor excitability after MF. Carbohydrate mouth rinse may be a valuable tool at combating the negative consequences of mental fatigue.