benzofurans and Dementia

Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.

Topics: Benzhydryl Compounds; Benzofurans; Cholinergic Antagonists; Cognition; Cognitive Dysfunction; Dementia; Humans; Mandelic Acids; Prodromal Symptoms; Pyrrolidines; Risk Assessment; Risk Factors; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

In recent years, L-3-n-butylphthalide (L-NBP) has been used for Parkinson disease dementia (PDD) to attenuate cognitive impairments in China. Therefore, we selected published and qualified clinical trials to conduct a systematic review and meta-analysis with the aim of assessing the effectiveness and safety of L-NBP in the treatment of PDD.. This systematic review and meta-analysis aimed to assess the effectiveness and safety of L-NBP in the treatment of PDD.. We searched PubMed, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database to collect eligible articles. We calculated pooled estimates of odds ratios or the standard mean deviation with 95% confidence intervals.. Eight randomized controlled trials were included in our meta-analysis. Our meta-analysis showed that L-NBP combined with Western medicine (WM) had a better effect on improving cognitive dysfunction, the total effective rate, symptoms of Parkinson disease (PD), and activities of daily living function than WM alone. Regarding safety, no serious adverse events were observed in the experimental group.. We found that L-NBP as a complementary therapy may have a positive therapeutic effect for improving cognitive dysfunction, the total effective rate, symptoms of PD, quality of life, and the related serum factors in the treatment of PDD. Furthermore, L-NBP was a safe treatment for PDD. However, the findings of our meta-analysis may be influenced by the low quality of the included studies. We highlight the need to conduct trials with higher methodological quality.

Topics: Antiparkinson Agents; Benzofurans; Capsules; Dementia; Humans; Nootropic Agents; Parkinson Disease; Randomized Controlled Trials as Topic

(11)C-Pittsburgh compound-B ((11)C-PiB) is the benchmark radiotracer for imaging of β-amyloid (Aβ) plaque in Alzheimer disease (AD). (18)F-labeled Aβ tracers subsequently developed for clinical use show higher nonspecific white matter binding and, in some cases, lower cortical binding in AD that could lead to less accurate interpretation of scans. We compared the cortical and white matter binding of a new (18)F-labeled Aβ tracer, (18)F-AZD4694 (recently renamed NAV4694), with (11)C-PiB in the same subjects.. Forty-five participants underwent PET imaging with (11)C-PiB and (18)F-AZD4694 (25 healthy elderly controls [HCs], 10 subjects with mild cognitive impairment, 7 subjects with probable AD, and 3 subjects with probable frontotemporal dementia). Images were coregistered so that region-of-interest placement was identical on both scans, and standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were calculated between 40 and 70 min after injection for both tracers.. (18)F-AZD4694 showed reversible binding kinetics similar to (11)C-PiB, reaching an apparent steady state at 50 min after injection. Both radiotracers showed a similar dynamic range of neocortical SUVR (1.1-3.3 and 1.0-3.2 SUVR for (11)C-PiB and (18)F-AZD4694, respectively) and identical low nonspecific white matter binding, with frontal cortex-to-white matter ratios of 0.7 ± 0.2 and 1.3 ± 0.2 for both radiotracers in HCs and AD subjects, respectively. There was an excellent linear correlation between (11)C-PiB and (18)F-AZD4694 neocortical SUVR (slope of 0.95, r = 0.99, P < 0.0001).. (18)F-AZD4694 displays imaging characteristics nearly identical to those of (11)C-PiB. The low white matter and high cortical binding in AD indicate that this tracer is well suited to both clinical and research use.

Topics: Aged; Aging; Amyloid beta-Peptides; Aniline Compounds; Benzofurans; Benzothiazoles; Brain; Dementia; Female; Humans; Hydrocarbons, Fluorinated; Male; Molecular Imaging; Positron-Emission Tomography; Thiazoles

The aim of this study was to investigate the protective effect of dl-3-n-butylphthalide (NBP) on brain damage in streptozotocin (STZ)-induced diabetic mice subjected to cerebral ischemia.. we pretreated diabetic mice with NBP orally for 4 weeks prior and 2 days after transient common carotid artery occlusion (CCAO) operation. Immunohistochemistry and transmission electron microscopy were performed to investigate the neuronal loss, astrocytes activation, amyloid-beta (Abeta) protein expression, and autophagy activation.. The results showed that diabetes increased stroke-induced neuronal loss, astrocytes activation, Abeta generation, and autophagy activity, while NBP administration attenuated these changes. Immunofluorescence double staining of Abeta with autophagosome-specific antibody LC3 showed that most elevated Abeta(+) signal was co-localized with LC3(+) signal.. Our finding suggests that NBP attenuates Abeta generation promoted by diabetes in ischemia might act through inhibiting abnormally activated neuronal autophagy. Therefore, treatment with NBP to modulate autophagy might provide a novel therapeutic strategy for diabetes by preventing ischemic brain damage and depressing the risk of post-stroke dementia.

Topics: Amyloid beta-Peptides; Animals; Autophagy; Benzofurans; Brain Ischemia; Dementia; Diabetes Mellitus, Experimental; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Neuroprotective Agents; Random Allocation; Treatment Outcome

Polychlorinated biphenyls (PCB)/polychlorinated dibenzofurans (PCDF) are known to affect central nervous functioning. In recent studies, elderly patients who have been exposed to these have been noted to have psychological deficits. There is little known about which test is sensitive to neurotoxins in cognitive evaluation. The objective of the present study was to compare the significance between selective psychological tests in cognitive assessment in PCB-laden elderly.. A retrospective PCB/PCDF exposed cohort was observed. Exposed elderly aged ≥ 60 years and registered in Central Health Administration were enrolled, and similar age- and sex-matched subjects served as non-exposed controls. The Mini-Mental State Examination (MMSE) and Attention and Digit Span (ADS) were tested in both groups. Student's t-test, χ(2) -test and linear regression models were used for statistical analysis..  A total of 165 exposed patients and 151 controls were analyzed. The exposed group included 49% men, a mean age of 69.3 ± 6.4 years and an education level of 4.0 ± 3.9 years. The controls included 52% men, a mean age of 69.9 ± 5.5 years and an education level of 4.5 ± 3.2 years. There was no statistical difference in MMSE before and after adjusting for the confounding variables of age, sex and education (P= 0.16 vs P= 0.12). However, ADS-forward and ADS-total scores showed a significant decline in the exposed subjects (P= 0.0001 vs P= 0.001). Using a linear regression among stratified PCB and cognitive functioning (≤30 ppb; 31-89; ≥90), a dose effect was found at the medium (31-89 ppb) and high exposure (≧90 ppb) levels.. Our observations showed attention and short-term memory were impaired in PCB-laden elderly patients. Higher exposure level showed lower cognitive functioning in ADS. The MMSE was insensitive to neurotoxins. The present study shows that the selective test has a decisive role in toxic-related cognitive assessments.

Topics: Aged; Benzofurans; Cognition Disorders; Cohort Studies; Dementia; Dibenzofurans, Polychlorinated; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Memory, Short-Term; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Polychlorinated Biphenyls; Retrospective Studies; Serial Learning; Sex Factors; Taiwan