Medications that Cause Memory Impairment

Leyda Villagrasa Mendez

RISE Program, Biology Department, UPR Cayey

Many commonly prescribed drugs can interfere with memory. Some examples of drugs that cause memory loss are: antianxiety drugs, cholesterol lowering drugs, antiseizure drugs, antidepresant drugs, narcotic painkillers, hypertension drugs, sleeping aids, and incontinence drugs. Studies have been made on how Rosuvastatin, antimuscarinics drugs ,aspirin, and morphine affect memory aspects. This review paper describes investigations which use laboratory rats to explain how drugs affect different aspects of memory. In addition, there is another investigation which describes the function of over active bladder medications in the detrusor muscle of the bladder. The last investigation uses a sample of two thousand three hundred men and women to describe the effects of aspirin in memory.

Introduction

Short-term memory refers to a short period of time ranging from 30 seconds to a few days during which recent information is recalled. Short-term memory by definition has a limited capacity. (Heerema 2013). On the other hand, long-term memory refers to when information is retained from a few days to decades. The more the information is used or repeated the more it is likely to become a part of our long-term memory. Long-term memory can store unlimited amounts of information (Cowan, 2008). Sometimes memory is impaired by medication, and there are different ways in which common medications can affect memory. The anti-seizure drugs decrease convulsions by lowering signals in the central nervous system and therefore causing memory loss. Sleeping aids and hypertension drugs act on many of the brain pathways and chemical messengers by

blocking the action of key chemical messengers in the brain, including norepinephrine and epinephrine. Incontinence drugs block the action of acetylcholine, a chemical messenger that mediates all sorts of functions in the body. In the brain, they inhibit activity in the memory and learning centers (Neel, 2013). A study found that Oxybutynin ER, an incontinence drug, causes brain memory to resemble ten years older memory (Kay et al. 2006). When people take cholesterol lowering drugs, these also lower the cholesterol of the brain which is vital for different mental processes. The lipids in the brain are important for nerve cell connections. (Neel, 2013). Rosuvastatin, an oral drug for lowering blood cholesterol levels, increases nitric oxide which prevents new memory formation and erases existing memory. In addition, statins adversely affect tau proteins, which are synthesized by brain cells to maintain structure. Tau proteins

stabilize the microtubules of the neurons (Avila, 2004). Also, statins interrupt the enzymatic pathway related to the production of cholesterol by glial cells. (Chimakurthy and Murthy ,2012) Different studies have been made on lab rats to measure the effects of statins in short-term memory and of morphine in stages of inhibitory avoidance memory. Other investigations have been made to see the cognitive effects of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and aspirin on a population of men and women older than 45 years. It also has been proven that antimuscarinic drugs affect memory of old patients.

Effects of Antimuscarinic drugs on Cognitive Function in older patients

Antimuscarinic drugs are used by patients who suffer from overactive bladder (OAB), a common condition that affects the elderly population. OAB is defined as urinary urgency, usually accompanied by frequency and excessive urination at night (Geller, 2012). There are five muscarinic receptors, namely M1, M2, M3, M4, and M5. These are membrane proteins that respond to the neurotransmitter acetylcholine. Antimuscarinic drugs act as antagonist at the muscarinic M3 receptors of the detrusor muscle of the bladder. In this way these drugs help the patients by being involved in the contraction and relaxation of the muscle. Most of these drugs better the symptoms of over active bladder patients while others lack selectivity for the M3 receptors and interact with other muscarinic receptors. The drugs that interact with the other muscarinic receptors can cause negative side effects like cognitive dysfunction, because M1 and M2

receptors have a role in mediating cognitive function. Antimuscarinic agents with selectivity to M3 receptors limit Central Nervous System penetration and offer a

reduced risk of unfavorable cognitive events. (Kay et. al 2005)

The effects of Curcumin and Rosuvastatin in short term memory loss

An investigation was carried out to examine how curcumin affects rosuvastatin-induced short-term memory loss. Curcumin raises brain serotin levels, and serotin plays an important role in short-term memory. Rosuvastatin is an oral drug for lowering blood cholesterol levels. This investigation utilized rats and placed them in various sample groups in order to study rosuvastatin-induced memory loss. The control group only consumed curcumin. On the other hand, the experimental group received curcumin in different concentrations and rosuvastatin in the same concentration. The negative control received only rosuvastatin. This treatment lasted 14 days. The evaluation came after the treatment. This included a runway panel that was made of a box with three divisions. The rats were placed at the starting point and observed to see how long it took them to cross the doors of the compartments. The investigators concluded that negative control group (the rats that had only taken rosuvastatin) took longer to cross the second and the third door. In contrast, the rats in the experimental group (that were given curcumin and rosuvastatin) demonstrated less time to cross the second and the third door. From these findings, it was inferred that latency to reach the goal was an

indicator of short-term memory loss related with rosuvastatin. (Chimakurthy and Murthy 2012). Short-term memory may last only for a few minutes, is of limited capacity in humans, and is of far less capacity in laboratory rats. Monkeys have a more related short-term memory to humans. Therefore, this same study should be done on animals that have a short-term memory more similar to humans.

The effects of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin in memory impairment

Nonsteroidal Anti-Inflammatory Drugs, Aspirin, and Cognitive Function in the Baltimore Longitudinal Study of Aging studied the different cognitive effects of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and aspirin on a sample of two thousand three hundred men and women older than 45 years. Their study showed how participants without dementia reacted to tests of verbal and nonverbal memory, attention, perceptual-motor speed, confrontation naming, executive function, and mental status. At each visit to the Gerontology Research Center in Baltimore, the participants reported if they used NSAID or aspirin. Then, they were exposed to different tests that measured their memory, attention, concentration, executive function, and mental status. To increase the special information provided by each neuropsychological test, separate regression models were constructed for each test as a dependent measure. Aspirin use was associated with poor performance on the tests related to memory, concentration, and

visual memory. NSAID users showed better performance on the test related to memory, concentration, and mental flexibility. (Waldstein et al. 2010) A limitation of the study was that some patients died while others left the investigation adversely affecting the results of the study.

The effects of morphine in the stages of inhibitory avoidance memory

The most important aim of this study is to investigate the exact time of morphine's effect on various stages of inhibitory avoidance memory (IA).This is a fear-aggravated test used to evaluate learning and memory in rodent. Rats learn to avoid an environment in which an aversive stimulus (such as a foot-shock) was previously delivered. Consequently, an amount of 7.5 mg/kg of morphine was injected to rats. The IA apparatus consisted of a dual chamber box separated by a wall divided into two equal sized compartments. One side was illuminated while the other was not. Further studies have shown that rats tend to move to darker sides. Therefore, the latency of each animal to cross to the dark compartment was recorded in order to measure IA memory lost. This study shows that pre-training administrations of morphine impaired the acquisition of IA memory as revealed by a decrease in step-through latency on the test day. After-training administration impaired the consolidation of IA memory, but immediate after-training administration did not impair IA memory consolidation. Immediate pre-test administration impaired

IA memory retrieval (Zarrindast et al. 2013). For future investigations a longer study with another medications should be carried out. A dose of a month or longer should be used because humans use medications for long periods of time .

Conclusions

After reviewing current scientific literature about the different medications that affect memory, we can conclude that Rosuvastatin affects short-term memory loss .It prevents memory formation by producing nitric oxide, interrupts enzymatic pathways and affects tau proteins. Curcumin has a protective effect against Rosuvastatin induced short-term memory loss. This study is important because as mentioned before cholesterol lowering drugs affect our memory by lowering the cholesterol needed by the brain. In another study NSAID users without dementia displayed less of a decline in their cognitive function. In contrast, aspirin use was associated with greater cognitive decline. This study of the effects of NSAIDs and aspirin in cognitive function is very important because it provides significant information regarding the maintenance of cognitive functions with aging. Also other investigations have shown that the consumption of morphine before the stage of acquisition affects not only the acquisition of memory, but also its early stages of consolidation. Manipulations in the administration of morphine before retrieval affect later stages of consolidation or retention besides the retrieval of memory. This investigation shows that IA in rats is highly related to the ability humans have to

remember things. All these investigations are important to better understand the effect of medications in our memory. There should be future studies in order to analyze in more detail how these drugs affect humans, and also to avoid the usage of drugs that cause memory loss. Many people depend on medications but what they do not know is that these medications may cause severe side effects.

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