Procaine compared with lidocaine for incidence of transient neurologic symptoms. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. The effects of procaine/haematoporphyrin on age-related decline: a double-blind trial. Is routine procaine spirit application necessary in the care of episiotomy wound? Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
Transient neurologic symptoms (TNS) have been reported to occur after 16% to 40% of ambulatory lidocaine spinal anesthetics. Patient discomfort and the possibility of underlying lidocaine neurotoxicity have prompted a search for alternative local anesthetic agents. We compared the incidence of TNS with procaine or lidocaine spinal anesthesia in a 2:1 dose ratio.
                Seventy outpatients undergoing knee arthroscopy were blindly randomized to receive either 100 mg hyperbaric procaine or 50 mg hyperbaric lidocaine. An interview by a blinded investigator established the presence or absence of TNS, defined as pain in the buttocks or lower extremities beginning within 24 hours of surgery. Onset of sensory and motor block, patient discomfort, supplemental anesthetics, and side effects were recorded by the unblinded managing anesthesia team. Anesthetic adequacy was determined from these data by a single blinded investigator. Hospital discharge time was recorded from the patient record. Groups were compared using appropriate statistics with a P < .05 considered significant.
                TNS occurred in 6% of procaine patients versus 31% of lidocaine patients (P = .007). Sensory block with procaine and lidocaine was similar, while motor block was decreased with procaine (P < .05). A trend toward a higher rate of block inadequacy (17% v 3%, P = .11) and intraoperative nausea (17% v 3%, P = .11) occurred with procaine. Average hospital discharge time with procaine was increased by 29 minutes (P < .05).
                The incidence of TNS was substantially lower with procaine than with lidocaine. However, procaine resulted in a lower overall quality of anesthesia and a prolonged average discharge time. If the shortfalls of procaine as studied can be overcome, it may provide a suitable alternative to lidocaine for outpatient spinal anesthesia to minimize the risk of TNS. High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking.
                To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance.
                Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA-DHA, 400 mg/d EPA-DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function.
                The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA-DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo.
                In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance. Cognitive impairment is a frequent manifestation of advanced human immunodeficiency virus (HIV) infection. The response to antiretroviral medication is often partial and poorly sustained. Recent studies suggest that free radical production within the CNS and neuronal apoptosis may play important roles in the pathogenesis of HIV dementia. We conducted a randomized double-blind, placebo-controlled trial using a parallel group, 2 x 2 factorial design evaluating deprenyl, a monoamine oxidase B inhibitor and putative anti-apoptotic agent, and thioctic acid, an antioxidant, in 36 patients with HIV-associated cognitive impairment. Both deprenyl and thioctic acid were well tolerated with few adverse events. Deprenyl recipients showed significant improvement on tests of verbal memory compared with patients not taking deprenyl. Thioctic acid treatment did not improve cognitive function. These results suggest that deprenyl treatment is associated with cognitive improvement in subjects with mild HIV-associated cognitive impairment, whereas thioctic acid has no benefit. A larger efficacy trial is needed to assess the long-term effect of deprenyl on cognitive performance in patients with HIV infection. A randomized, double-blind study of procaine/haematoporphyrin (KH3) has been carried out over two years in a selected population of healthy elderly subjects. The period of study exceeds 500 patient years. The trial population was weighted to contain a larger proportion of subjects aged over 75 years than a standard population; those receiving active KH3 had similar characteristics on entry to those receiving placebo. Over the course of two years, KH3 was shown to be an active substance in that: (a) decrement in the consolidation of new learning was prevented in the treatment group (less than 1.0%, as against 38% in the placebo group); (b) the prevalence of incontinence increased significantly in the placebo group, but not in the active group (P less than 0.05); (c) there was a significant increase in grip strength in the active treatment group (+22%, P less than 0.01 v. placebo); (d) more adverse reactions were observed on treatment with KH3 (P less than 0.005). A randomised controlled trial to investigate the usefulness of local application of procaine spirit versus cleansing with water for care of episiotomy wound after normal vaginal delivery was conducted in 100 women.
                Fifty women entered the study arm and 50 entered the control arm of the study. Women in the two arms were similar in their demographic and obstetric characteristics.
                The pain scores on a verbal analogue scale was highest (score = 2.5) on Day 1 of the delivery. This was the same in women in both arms. The number of paracetamol tablets consumed was also low and was similar in both groups of women. By the fourteenth day of delivery, all the women were pain-free and the wound had healed well. It was noted that all the women maintained a high standard of perineal hygiene with a mean of 5 washes a day.
                It is concluded that in a woman with normal vaginal delivery, local application of procaine spirit is unnecessary in the care of a routine episiotomy wound. Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain.
                Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter.
                All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance.
                HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory.
                The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women.
                This study was a randomized, double-blind, placebo-controlled clinical trial.
                Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI).
                Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied.
                Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE + MPA) or placebo.
                Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.
                CEE + MPA had a negative impact on verbal memory (P <or= 0.01) and a trend to a positive impact on figural memory (P = 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms.
                The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research. Increased consumption of n-3 (omega-3) long-chain polyunsaturated fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life.
                We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people.
                At total of 867 cognitively healthy adults, aged 70-79 y, from 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study.
                The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (+/-SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 +/- 2.7 mg EPA/L in the active arm compared with 39.1 +/- 3.1 mg EPA/L in the placebo arm; 95.6 +/- 3.1 mg DHA/L in the active arm compared with 70.7 +/- 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome.
                Cognitive function did not decline in either study arm over 24 mo. The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study. The Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) Study was registered at www.controlled-trials.com as ISRCTN 72331636. Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.
This review suggests that the evidence for detrimental effects of procaine and its preparations is stronger than the evidence for benefit in preventing and/or treating dementia or cognitive impairment.
There is some evidence from older studies that procaine preparations might improve memory in persons without cognitive impairment. However, the clear evidence of side effects suggests that the risks might outweigh the benefits. In the light of this, the strong marketing claims for procaine preparations should be withdrawn until trials of adequate size, duration and quality have been conducted.