sildenafil-citrate and Cognitive-Dysfunction

The objective of this paper is to look at how natural medicines can improve cognition and memory when used with sildenafil, a popular erectile dysfunction medicine that also has nootropic properties. Newer treatment strategies to treat the early stages of these diseases need to be developed. Multiple factors lead to complex pathophysiological conditions, which are responsible for various long-term complications. In this review, a combination of treatments targeting these pathologies is discussed. These combinations may help manage early and later phases of cognitive impairments. The purpose of this article is to discuss a link between these pathologies and a combinational approach with the objective of considering newer therapeutic strategies in the treatment of cognitive impairments. The natural drugs and their ingredients play a major role in the management of disease progression. Additionally, their combination with sildenafil allows for more efficacy and better response. Studies showing the effectiveness of natural drugs and sildenafil are mentioned, and how these combinations could be beneficial for the treatment of cognitive impairments and amnesia are summarised. Furthermore, preclinical and clinical trials are required to explore the medicinal potential of these drug combinations.

Topics: Amnesia; Cognition; Cognition Disorders; Cognitive Dysfunction; Humans; Male; Sildenafil Citrate

and purpose: In this study, we employed a multiple microinfarction (MMI) based vascular dementia (VaD) model in aged rats and tested the therapeutic effects of Sildenafil, a phosphodiesterase type 5 inhibitor, on cognitive decline, white matter damage, autophagy and inflammatory response associated with VaD.. Male, aged (16-18 months) Wistar rats were subjected to MMI (800 ± 100, 70-100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days. Four experimental groups were employed: Sham control, Sham + Sildenafil, MMI, and MMI + Sildenafil. A battery of cognitive tests were performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation and PCR assay.. Sildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats. Sildenafil treatment of aged MMI rats significantly increases axon and myelin density in the corpus callosum and white matter bundles in the striatum, increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum, and increases synaptic protein expression in the cortex and striatum compared to aged control MMI rats. In addition, Sildenafil treatment of MMI in aged rats significantly decreases Beclin1 expression and inflammatory factors Monocyte chemoattractant protein-1 and Interleukin-1β expression in brain. Sildenafil treatment in aged rats does not improve cognitive outcome compared to aged sham control rats.. Sildenafil treatment of MMI in aged rats significantly improves cognition and memory at 1 month after MMI. Sildenafil treatment increases axon and myelin density, increases Synaptophysin expression, decreases autophagic activity and exerts anti-inflammatory effects which in concert may contribute to cognitive improvement in aged rats subjected to MMI.

Topics: Aging; Animals; Brain; Cognition; Cognitive Dysfunction; Dementia, Vascular; Disease Models, Animal; Male; Maze Learning; Myelin Sheath; Neuroprotective Agents; Rats, Wistar; Sildenafil Citrate

Alzheimer's disease (AD) is the most common cause of neurodegenerative cognitive impairment, defined by abnormal accumulations of amyloid-β and tau. Approaches directly targeting these proteins have not resulted in a disease modifying therapy. Neurovascular unit dysfunction is a feature of AD offering an alternative target for intervention. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, improves cognitive functioning in mouse models of AD. Recent work in AD patients has demonstrated increased cerebral blood flow, as well as brain oxygen utilization after a single dose of sildenafil. Its effect on nitric oxide-cGMP signaling may have downstream effects on neuroplasticity, amyloid-β processing, and improved neurovascular unit function. Fractional amplitude of low frequency fluctuations (fALFF) assesses spontaneous neural activity via resting state fMRI BOLD signal (0.01-0.08 or 0.10 Hz). In AD, other assessments have revealed increased fALFF in hippocampi and parahippocampal gyri. Here, we examined the effects of a single dose of sildenafil on fALFF in a cohort of 10 AD patients. We found a decrease (p < 0.03, α= 0.05) in fALFF an hour after sildenafil administration in the right hippocampus. Additionally, cerebral vascular reactivity in response to carbon dioxide inhalation, a measure of neural vascular reserve previously collected on most of these participants, was not significantly correlated with this decrease, implying that change in fALFF may not have been solely due to altered vascular reactivity to CO2. We demonstrate that in patients with AD, hippocampal fALFF decreases in response to sildenafil, suggesting a normalization. These findings support further investigation into the effects of sildenafil in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Cognitive Dysfunction; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Pilot Projects; Sildenafil Citrate; Temporal Lobe