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Replies to post #173539 on Anavex Life Sciences Corp (AVXL)
Neurogenesis in the adult hippocampus is regulated by numerous environmental, physiological, and behavioral factors known to affect learning and memory. Sleep is also important for learning and memory. ... The mechanisms by which sleep disruption inhibits neurogenesis are not fully understood.
Sleep and adult neurogenesis: implications for cognition and mood.
https://www.ncbi.nlm.nih.gov/pubmed/24218292
Despite the promising results of AAV2-GAD, the precise mechanisms behind it remained unclear.
Scientists hypothesized, however, that the local delivery of the GAD gene to induce the production of GAD and GABA would convert STN nerve cells to a suppressive state and reduce their hyperactivity, ultimately easing Parkinson’s motor symptoms.
Sleep Fragmentation
Sleep fragmentation is probably the most common nocturnal complaint in Parkinson’s disease. Several studies analyzing sleep patterns in Parkinson’s Disease have found that the sleep pattern is more frequently interrupted and that the amount of time spent in slow-wave and REM sleep (the deepest and most restorative phases of sleep) is significantly less than that of age-matched adults without Pakinson’s. This type of sleep disturbance may be associated with a greater susceptibility to medication-induced hallucinations as well as excessive daytime sleepiness.
Medications for Sleep Fragmentation
Sleep fragmentation is best treated by the use of the long-acting sedative clonazepam (Klonopin) taken at bedtime. Clonazepam, rather than being immediately sedating, tends to help regulate sleep and allow for a more normal nighttime sleeping pattern.
(My comment - clonazepam causes mitochondiral dysfunction so this is probably not a good idea.)
Another alternative is to try and treat excessive daytime sleepiness, which often goes hand-in-hand with sleep disturbance. This may involve alterations in anti-PD drugs (as many of them can cause sedation when taken during the day or disrupt sleep patterns when taken at night) or the addition of a stimulant medication. One such medication is modafinil (Provigil), which is used in narcolepsy and has been found to help daytime sleepiness and fatigue in PD. True stimulants such as methylphenidate (Ritalin) have been used for excessive daytime sleepiness in persons with Parkinson’s disease as well, but should be used with particular care in persons with cardiovascular disease.
Nighttime urinary frequency
Nighttime urinary frequency is usually a result of autonomic dysfunction, which nearly all Parkinson’s disease patients experience in one form or another. It is characterized by an increased sense of urgency, hesitancy and increased frequency, particularly at night. In new cases, other treatable and potentially serious causes such as infections, prostate difficulties (in men), and other renal or circulatory dysfunction should be ruled out first.
For simple nighttime urinary frequency, anticholinergic medications such as darifenacin (Enablex), solifenacin (Vesicare), tolterodine (Detrol) and oxybutinin (ditropan) are often helpful. In some cases the hormone ddAVP taken as a nasal spray at bedtime has been used with good effects. If the problem persists a formal urologic evaluation may be necessary. While the causes of nighttime difficulties in Parkinson’s disease are varied and often complex, it is important to know that potential solutions do exist, and that no one should have to “just live with it”.
(oops, Google anticholinergic, mitochondrial disease, not such a good idea it seems)
REM behavioral disorder
REM behavioral disorder (RBD), often described by patients and family members as “thrashing about” in sleep or “acting out” of dreams, is a result of impaired sleep paralysis that can manifest in patients with Parkinson’s Disease and other neurodegenerative conditions. It is more frequently encountered in males with Parkinson’s Disease than females. Patients often describe vivid dreams that can range from friendly and pleasant to being quite menacing and frightening. It is theorized that excess nighttime levels of dopaminergic medications (L-dopa and dopamine agonists) may exacerbate this phenomenon.
The treatment of choice is clonazepam, which is effective in 75-90 percent of cases in the general population. Alternatively certain antidepressants, such as bupropion (Wellbutrin) and sertraline (Zoloft) may be helpful in some individuals. Conversely, individuals with newly diagnosed Parkinson’s disease who have RBD symptoms often report resolution of this sleep disturbance when they begin treating their Parkinson’s disease with dopaminergic medications.
(another oopsie antidepressants screw up the mitochodria too)
Nighttime Hallucinations, Psychosis, & Confusion
Nighttime hallucinations and confusion (also referred to as psychosis) may result from any combination of cognitive impairment, dopaminergic medications, age and PD-related vision changes and lack of sleep. Psychosis may first appear after infection, trauma, surgery or prolonged hospitalization. Symptoms may range from a sensation that someone or something is standing at the side of or behind the person, to very detailed and often frightening visions. Delusions (often paranoid in nature) may occur as well.
Treating Parkinson’s Psychosis
The first-line approach to treatment of PD psychosis involves simplification of the anti-PD medication regimen and adjusting dose timing (decreasing or eliminating end of day doses), treating other sleep disturbances, providing a consistent and familiar sleep environment (the use of a night light is often very helpful), and in more severe cases, the use of atypical antipsychotic drugs.
Most of the available anti-psychotics are always avoided in PD psychosis because they block dopamine receptors and can cause significant problems with movement. However, two anti-psychotic medications, quetiapine and clozapine, are sometimes used as they have less of an ability to worsen motor symptoms. However, data for the use of quetiapine is limited and clozapine requires the patient to undergo frequent blood draws to monitor blood counts. A newer medication pimavanserin, was approved by the FDA to treat PD psychosis. It has a different mechanism of action, and does not block the dopamine system, but rather the serotonin system, and therefore does not increase motor symptoms.
(okaaay.. so now we're going to block the serotonin system. Didn't the article just recommend SSRI's?)
Steps to Sleeping Better
Beyond receiving treatment, there are steps you can take personally to improve your sleep. Particularly when dealing with issues such as difficulty maintaining sleep at night and excessive sleepiness during the day, the concept of sleep hygiene is crucial. Sleep hygiene refers to the behaviors and habits that we can control that affect our bodies day-night cycling and readiness to go to sleep or be alert at a given time of day. Follow these tips for better sleeping habits:
It is especially important for individuals with sleep difficulties to set and follow regular bed/sleep and wake times with a goal of spending at least 7 but not much more than 8 hours in bed each night. Bedtimes should be chosen based on a target waking time (i.e. don’t go to bed at 8 pm if you don’t want to be up at 4 am!).
The bed should be used only as a place of sleeping, reading and watching television should be done elsewhere.
Daytime napping should be limited to one nap of no greater than 30 minutes, as longer naps do not seem to provide any greater benefit to daytime fatigue but do disrupt sleep drive for the coming night.
Lastly it is vital that persons with these sleep disorders are exposed to as much light (preferably real daylight) and physical/mental stimulation during the day as possible. Light is an important synchronizer of the sleep-wake cycle and many elderly individuals and individuals with chronic illness have reduced exposure to bright light.
Physical and mental activity stimulates the alerting and wakefulness centers in the brain and increase blood and oxygen flow to the brain. Most importantly, maintaining good sleep and wake habits can improve many sleep issues without the need of medications.
