Memory+(Vivian,+Nicole,+Mandy,+Kathleen)

Vivian Pak 08632439T Olivia Cheung 08609891T Kathleen Ng 08624753T Mandy Tsang 08653539T

**Alzheimer's Disease - The Memory Thief!** Our brain stores every precious and memorable scene in our lives, but unfortunately, they do not last forever. Alzheimer’s disease (“AD”), also known as the memory thief, will one day steal all those treasured moments away. The sufferers, who have memory loss, forget what they have done, where they live, and also who their beloved ones are. To have more understanding of this disease, biological mechanism for memory, orientation of memory loss in AD patients, changes in their brain tissue, progression of memory deficits, and related medical and non-medical treatments such as coping skills to enhance their daily life are explored in the following sections.
 * Introduction**


 * Part 1 - Memories, brain, and long-term potentiation (by Kathleen Ng)**
 * Types of Long-term memories**

Memory refers to the capacity of information storage and retrieval (Gerrig & Zimbardo, 2008). Memory can be used to consciously recall information, and remember how things are done. However, memory that we are using instantly is different from those are stored in an inactive state. Donald Hebb (Kalat, 2009) distinguished between long-term memory (LTM) and short-term memory (STM) according to their capacity and retrieval ability. He suggested STM is dealing with events that just happened instantly, while LTM is working on events in further past.

In LTM, there are two categories, declarative memory and procedural memory. Declarative memory refers to the recollection of facts and events (Gerrig & Zimbardo, 2008), whereas procedural memory is responsible for storing skills (Hunt & Ellis, 2004).

Endel Tulving (Hunt & Ellis, 2004) proposed memory for an event is different from that for general knowledge. He defined the former one as episodic memory, and the latter is semantic memory. Episodic memory records specific events that have personally experienced, for example, memories of the first day in university. It can be easily recovered by retrieval cues that contain specific contents or time related to the single event. Semantic memory, however, is generic and categorical (Gerrig & Zimbardo, 2008). It stores general knowledges and facts, such as, 1st July is the HKSAR Establishment Day. Both episodic and semantic memories are cognitive and conscious in sense, and can be easily declared, so they are explicit memories.

Procedural memory, as mentioned above, stores the procedures for motor and cognitive skills (Hunt & Ellis, 2004). Driving, typing, and using mathematic rules are the examples of using procedural memory. The operation of procedural memory, rather than requiring conscious control, is automatic and non-verbalized. It is difficult to describe how to ride a bicycle in words. Therefore, procedural memory is regarded as implicit.

Spatial memory is the memory for recording the internal cognitive map of a general picture of the environment (Gerrig & Zimbardo, 2008). The cognitive map helps work out the spatial congfiguration and navigates the paths for targeted locations (Newman et al, 2007). For example, taxi drivers, with strong spatial memory, can easily find the most ideal route between the start point and the destination.


 * Brain structures involved in memory**

After the case of H.M., researchers noticed that hippocampus is crucial for memory formation and retrieval. Hippocampus is also important for consolidation of LTM, as well as storage of episodic memory that patient with hippocampal damage will suffer from anterograde amnesia and he could not remember events happened after the surgery. Besides, it is also responsible for spatial memory. The Morris water maze task found rats with hippocampal damage were difficult to find their ways if they started at different location of the maze. (Kalat, 2009)

H.M. not only had his hippocampus removed, but also amygdala (Kalat, 2009), which is important for emotional memory, especially fearful experience (Gerrig & Zimbardo, 2008). A moderate amount of cortisol, which is secreted in an exciting emotion, can activate amygdala and hippocampus, so that the storage and consolidation of recent events can be enhanced (Kalat, 2009).

Among declarative memories, episodic memory is stored in hippocampus, while semantic memory is kept in the anterior and inferior temporal lobe. However, it is not only the place for storage, but also serves as a communication center between different brain areas for gathering all semantic memory (Kalat, 2009).

Procedural memory relies on different brain structure with declarative memory. Researchers, with the help of fMRI, they found that it depends on basal ganglia (Kalat, 2009), which consists of caudate nucleus, putamen, and globus pallidus.

Several studies mentioned medial temporal lobe (MTL) involves in memory (Dickerson & Eichenbaum, 2010; Greenberg, Keane, Ryan, & Verfaellie, 2009; Sperling et al., 2010). Hippocampal formation is a structure in MTL that consist the limbic system, dentate gyrus, hippocampus proper, and subiculum. It was found related to spatial memory and verbal information processing (Carlson, 2011).


 * Long-term Potentiation**

Learning and memory are interrelated. Information is memorized through learning because of the synaptic changes in the brain. Long-term potentiation (LTP) is the model explaining memory formation in a cellular perspective. The phenomenon of LTP was first discovered by Terje Lømo in 1966 (Bliss, Collingridge & Morris, 2004). LTP refers to the strength of synapses between neurons in the central nervous system is enhanced for a prolonged period, from few minutes to several weeks, after a series of rapid, intense stimulation (Bliss, Collingridge & Morris, 2004). The synaptic strength is “potentiated”, and it is more responsive to stimulations.

media type="youtube" key="sTPa2rvqDWs" height="315" width="420"


 * Biochemical Mechanisms of LTP**

Glutamate is one of the important neurotransmitter for LTP. Two iontropic glutamate receptors, AMPA and NMDA, locate on the dendrites. When the action potentials travel down the axon, glutamate molecules are released to the synaptic cleft, then attach to the AMPA and NMDA receptors. When the AMPA receptor stimulated, it is open to sodium ions to enter the post-synaptic cell. However, the NMDA receptor fails to open because magnesium ion is blocking the channel, and it prevents ions from entering the NMDA receptor channel. At this stage, only sodium ions enter the dendrite through AMPA receptors, and it becomes more depolarized. The depolarization displaces magnesium ion, which blocks the NMDA receptor. By the stimulation of glutamate, NMDA receptors open and allow not only sodium ions, but also calcium ions, which are crucial to further process, entering the dendrite. A protein called CaMKII, which is important for LTP, is activated by calcium in dendrite, then starts a series of processes to undergo LTP. There are four ways in which LTP occurs. Firstly, the dendrites make more new AMPA receptors and relocate the old to a more ideal position. Secondly, more NMDA receptors are also made on dendrites. The expanded numbers of AMPA and NMDA receptors increases the chance of receptors being stimulated, thus shorten the time for the dendrites being depolarized. Thirdly, more dendritic branches are formed to make more synapses to the same axon. It is the result of frequent stimulation that increases the sprouting of dendrites, which also contribute to the whole process. Lastly, some AMPA receptors become potentiated. It is more easily to response to stimulation by glutamate, then open channel for sodium ions, thus fasten the overall operation. Researchers found even if the NMDA receptor is blocked, the created LTP can still be maintained (Kalat, 2009). This means, no matter what state of NMDA is, the AMPA receptor will keep potentiated after the development of LTP.


 * Part 2 - Why can’t Alzheimer’s Disease (AD) Patients hold tight to their memories? (By Olivia Cheung**)

media type="youtube" key="0pAJD8Q2bKY" height="315" width="420"
 * The life of AD patients**

media type="youtube" key="xDvvMpuJFsw" height="315" width="560"


 * What is AD?**

Alzheimer’s Disease (AD), also known as senile dementia, is the most common form of dementia. It takes up 60% of all dementias. It was named after Alois Alzheimer who first described this disease in 1906 (Niedermeyer & Ghigo, 2011). AD is more common in people over 65 years of age with almost 50% of people over 85. AD is receiving more attention nowadays due to an increase in its global prevalence. It is projected that the number of people with dementia will increase to an estimate of 8.1 million by year 2040 (Gallagher et al., 2011). As disease progresses, AD patients suffer from more cognitive impairments such as memory loss, confusion, depression, agitation so on and so forth (Kalat, 2009). AD is described as an incurable, degenerative and fatal disease.

The early stage of AD is marked by memory loss (Niedermeyer & Ghigo, 2011) and such loss is conceptualized as consolidation deficiency (Dickerson & Eichenbaum, 2010). Patients with AD have problem forming recent memories while their remote memories are not as much affected (Kertesz & Kertesz, 1988). The memory loss is the result of the deterioration in hippocampus where memory is primarily tied to (Niedermeyer & Ghigo, 2011). Hippocampal atrophy is found in AD with a mean volume loss of between 20% and 52% in AD patients compared with age-matched controls. Studies found that hippocampal atrophy is associated with the level of neuro-physiological activity in the left temporal lobe. This indicated that there may be some cognitive impairment in hippocampal atrophy itself. Accordingly, it is postulated that an atrophied hippocampus may not be able to integrate memories in the neocortex (Dhikav & Anand, 2011).

**Different stage of hippocampal atrophy ** Image adapted from google.com Adapted from Fotuhi, M. //Changing Perspectives Regarding Aging and Alzheimer’s Disease// [PowerPoint slides]
 * Comparison of hippocampus in healthy person and an AD patient**


 * What role does hippocampus play in memory formation?**

The function of hippocampal formation in memory formation is to bind individual, isolated memories together in a way that permits us to remember the association among the elements of memories. This process is referred to as consolidation. In the course of consolidation, hippocampus receives and processes information from sensory and motor association cortices and from some sub-cortical regions such as basal ganglia and amygdala. Through its efferent connections with these regions, consolidated memories are being modified in hippocampus before they are sent to the cerebral cortex for permanent storage. In short, STM is consolidated into LTM in time (Carlson, 2011).



Memories exist in two states; namely labile state and stable state. Memory in a labile state is vulnerable to enhancement and impairment whereas memory in a stable state is more resistant to changes (Nader & Hardt, 2009). As memory of new learning is in a labile state, therefore it is subject to changes before it is consolidated and stored in LTM.

The Morris water maze task experiment revealed that hippocampal damage leads to impairment in spatial memory performance (Kalat, 2009). During the experiment, unlike the control mice, the hippocampal lesioned mice swam in an aimless fashion until they found the floating platform which was submerged in the murky water when they were released from a different point on each trial, however, they showed no sign of this impairment if they were released from the same point on each trial. The result of this experiment suggested that hippocampal lesioned mice are unable to perform relational learning. Indeed, several other experiments found that the hippocampal formation has the function of consolidating relational memories (Carlson, 2011).

Another experiment found that mice with hippocampal lesion showed deficiency in performing what they had learned from the training a day before they had the surgery, however, they showed no problem of performance when they received hippocampal lesion 42 days after the training. Therefore, it is conclused that hippocampal lesions interrupt recently acquired memories, but not remotely acquired memories (Wang, Teixeira, Wheeler & Frankland, 2009). Note: A = Context A, B = Context B Adapted from Wang, S. H., Teixeira, C. M., and Wheeler, A. L. //Nature Neuroscience,// //2009////, 12// (3), 253-25

The results of the above experiments indicate that memory of new learning cannot be consolidated from STM to LTM when hippocampus is damaged. Therefore, hippocampal damage impairs the process of consolidation.

Broadly speaking, memories once go through consolidation are stored in the neocortex and are resistant to hippocampal damage (Graham & Hodges, 1997). The LTM becomes insensitive and stable. If this is the case, then why we see LTM impairment in AD patients in their late AD stage. Recent findings argued that these insensitive memories can be reverted to a sensitive state by simply remembering them (Nader & Hardt, 2009). Lewis (1979) pointed out that new and reactivated memories are in an active memory. Furthermore, when these insensitive memories are being reactivated, they will return to a labile state (Ohno, 2009). In fact, the reactivated memories through retrieval must again reconsolidate and restabilize so that they can be ‘returned’ to LTM for storage (Nader & Hardt, 2009). This process is called reconsolidation.



An experiment on reconsolidation data from an auditory fear-conditioning study was conducted to test how the treated mice responded to post-reactivation short-term memory (PR-STM) and post-reactivation long-term memory (PR-LTM). They were infused with anisomycin or vehicle into their amygdale when their memory of prior training on pairing a tone with a foodshock was fully consolidated and reactivated by presentation of the tone alone. It was found that they responded to the tone almost as good as the control mice four hours after the treatment (PR-STM test). In contrast, they had problem responding to the tone twenty hours after PR-STM test. As a result, reconsolidation deficit was found in the treated mice; i.e. impairment is seen in PR-LTM but not PR-STM (Nader & Hardt, 2009).

Adapted from Nader, K., and Hardt, O. //Nature Reviews Neuroscience,// 2009, //10,// 3, 224-234.

We see from the above experiment that the treatment on the treated mice’s amygdala disrupted the reconsolidation process. However, molecular mechanisms or brain regions that are required in this process are still not yet defined. Study suggested that they are not necessary the same area as that are involved in the process of consolidation (Ohno, 2009).

Hippocampus is crucial for maintaining recently learned memory, the frontal, parietal and temporal lobes are responsible for the maintaining remote memories (Whalley, 2009). Wang et al. (2009) stated in their research that “without the hippocampus, the memory is more fragile, the integrity of the hippocampus is important for robust memory expression” (p. 255). We can see that hippocampus plays a vital role in memory formation, be it short-term or long-term. Affected by consolidation deficit, AD patients are unable to form new memories; moreover, the disruption of reconsolidation further weakens their memory trace and eventually worsens their cognitive decline (Ohno, 2009).

The causes and progression of AD have not yet fully understood. Yet there are different hypothesis, be it the genetic outcome, environmental influnces or lifestyle factors. In this regard, the researchers are seeking the ways to prevent suffering from AD or the possible cures for AD patients.
 * Part 3 -** **Uncovering the mystery - in the brains of Alzheimer’s Disease patients (by Vivian Pak)**

Alzheimer's Disease - Environment, Lifestyle, Diet and Exercise media type="youtube" key="h4ZovSpPpAI" height="315" width="560"

The level of exposure to these risk factors varies with each individual. However, it is commonly believed that a complex series of events take place in AD patients' brains over period of time.


 * Hallmarks of AD - abnormal clumps, i.e. amyloid plaques & tangles**

Two abnormal protein fragments, called amyloid plaques and tangles, are classic biological hallmarks of AD. In the research conducted by Tiraboschi and his team, the level of plaques and tangles in different brain regions were measured among 102 patients with AD having all stages of disease and 29 normal control subjects through autopsy study. There was significant difference in levels of plaques between AD patients and control subjects which supported the hypothesis that the deposition of plaques occurred early in the course of AD. Whereas the tangles were highly correlated with level of cognitive impairment among the patients. (Tiraboschi, Hansen, Thal & Corey-bloom, 2004) However, the finding is inconsistent with other previous studies of showing a closer relationship between AD severity and plaques. The possible reason may come from different instruments used for severity measurement.

Amyloid plaque is a largely insoluble deposit of toxic protein peptide, called β-amyloid found in the brain that exists in the space between nerve cells. It is a residual part as a result of abnormal cuts by enzymes beta-secretase and Gamma-secretase to Amyloid precursor protein that contributes to neuron growth, survival and post-injury repair. β-amyloid is accumulated and begins to clump with others, forming oligomers then eventually becoming plaques. (Alzheimer's Disease Education & Referral Center, 2011) However, it is ambiguous that amyloid plaques themselves cause AD or just a by-product of AD process. In this regard, scientists viewed that these plaques might cause all of the damage to neurons.



Tangles are aggregates of microtubule-associated protein tau. In a healthy brain, tau protein binds and stabilizes microtubules critical to the cell’s internal transport system and responsible for transporting nutrients and other components along the axon. Instead, in the patient’s brain, tau collapses from the microtubules. These twisted strands combine to form tangles inside the neuron so the transport system of neuron dysfunctions and the nerve cell is destroyed. (Alzheimer's Disease Education & Referral Center, 2011) The consequence is neurons disconnect from each other and die eventually. Plaques and tangles may lead possible damage to synapses and LTP may not perform due to the gradual loss of connections between neurons.

Inside the Brain: Unraveling the Mystery of Alzheimer's Disease [1:07 - 3:21]

media type="youtube" key="NjgBnx1jVIU" height="315" width="560"

These toxic structures are accumulated in the brain and start from hippocampus where memory first formed as mentioned in the previous part and slowly destroy the hippocampus over the years, becomes harder and harder to form new memory. After that, more plaques and tangles will spread into other different regions of the brain, killing cells and comprising the functions where they go. Dispreading around is what leads to the different stages of AD.




 * Memory Impairment in different stages of AD**

Many people likely put a stigma of AD to the people with deterioration of memory function. Actually, in the early stage of AD, memory deficit is the most prominent feature of AD (Forstl & Kurz, 1999), like the patients may find difficult to remember recent events. The progression from mild to death is slow and steady and takes place over an average of 10 to 20 years. ( Alzheimer’s Disease Education & Referral Center, 2010 ) They also progressively suffer other functional problems, e.g. language, social skills and problem solving.

AD patients demonstrate an order of memory loss. (Kertesz & Kertesz, 1988) Some researchers thought that the declarative recent memory would be first impaired among AD patients in the mild stage. (Dreging et al., 1994) Rather their remote episodic memory, e.g. older memories of their life, semantic memory, e.g. facts learnt and implicit memory, e.g. procedural memory are affected in lesser degree (Forstl & Kurz, 1999; Jelicic, Bonebakker & Bonke, 1995) by noting the retention of language and other forms of cognitive function (Kertesz & Kertesz, 1988). On the other hand, some researchers found that AD patients in this mild stage also have a deficit of short-term memory as proved by their reduced digit span. (Forstl & Kurz, 1999) Different degrees of memory impairment hinder patients' various cognitive domains that affect their daily livings. Some common memory deficits are found in this stage including difficulty in new learning or resistance to changes or new things due to shorter attention span and less motivation to their easy loss of way goint to familiar places. (Forstl & Kurz, 1999) Forgetfulness is always a problem, e.g. forgetting to eat, misplacing things in odd places such as putting wallet in toilet, forgetting where things go such as looking for a tooth brush in the kitchen, forgetting to pay or pay too much. (Alzheimer's Disease Education & Referral Center, 2009)

老年癡呆症照顧篇 [0:00 - 3:05]

media type="youtube" key="7_KpW-FJ0ZM" height="315" width="420"

<span style="font-family: '新細明體','serif'; font-size: 16px;">老年癡呆症 <span style="font-family: 'times new roman','serif'; font-size: 16px;">[ <span style="font-family: '新細明體','serif'; font-size: 16px;">腦退化症 <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">] [0:59-3:42] <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">media type="youtube" key="snUKD3Zpg6I" height="315" width="420"

In the moderate stage, semantic memory would be further affected. Language difficulties become more obvious due to impoverishment of vocabulary, difficulties in finding words or paraphasias. (Kertesz & Kertesz, 1988; Forstl & Kurz, 1999) Lesser words would be used in their speech by a descending order of consumption in nouns, adjectives and verbs. (Kertesz & Kertesz, 1988) They may continuously repeat stories or favorite words. Somehow they cannot name the objects but still can demonstrate how to use them. (Forstl & Kurz, 1999) The patients in this stage may mix up the identity of people, e.g. thinking a wife is a stranger or thinking a daughter is an auntie, unable to recognize their belongings or forget to switch off the electrical appliances, e.g. gas stove. Or they may even have illusion or delusional symptoms and other intellectual deficits. (Alzheimer’s Disease Education & Referral Center, 2009)

media type="youtube" key="tsG4lCi2E8o" height="315" width="420"
 * 老年癡呆症照顧篇 **** ( **** 二 **** ) **** 中度至嚴重程 **** 度 ** [0:00 - 4:31]

In the final severe stage, all cognitive domains are seriously impaired. "Even early biographical memories can be lost." (Forstl & Kurz, 1999) The patients do not recognize themselves and eventually their procedural memory would be lost, e.g. inability to walk, eat and drink. Afterwards, they become bedridden till death. (Kertesz & Kertesz, 1988; Alzheimer's Disease Education & Referral Center, 2009)

Although there is currently no way to cure Alzheimer's disease or stop its progression, researchers are making encouraging advances in Alzheimer's treatment. The most commonly used drugs to treat AD are as follows: **Mild/Moderate AD:** 1. Cholinesterase inhibitors increase the levels of acetylcholine in the brain, which plays a key role in memory and learning. This kind of drug postpones the worsening of symptoms for 6 to 12 months in about half of the people who take it. Cholinesterase inhibitors most commonly prescribed for mild to moderate AD include: l Aricept (donezepil HCL) l Exelon (rivastigmine) l Razadyne (galantamine) Treating Alzheimer's Disease (Alzheimers #3) [0:00-1:45] media type="youtube" key="PLW1xZN98V8" height="315" width="420" **Aricept (Donepizel)** Aricept is Food and Drug Administration (FDA)-approved for mild, moderate, and severe stages of the disease. It is available in tablet form or an orally disintegrating tablet form, and is commonly started at 5 mg a day. It can cross the blood-brain barrier.
 * Part 4 - Treatment (by Mandy Tsang)**
 * Exelon (Rivastigmine)**

Exelon is a cholinesterase inhibitor that prevents the breakdown of acetylcholine and butyrylcholine in the brain by blocking the activity of two different enzymes. Acetylcholine and butyrylcholine play a key role in memory and learning. It is available as a capsule, liquid, and patch. When given orally, bioavailability is about 40% in the 3 mg dose. The compound can cross the blood-brain barrier. **Razadyne (galantamine HBr)**

Razadyne is FDA-approved for mild and moderate stages of the disease.Acetylcholine plays a key role in memory and learning; higher levels in the brain help nerve cells communicate more efficiently. Razadyne also stimulates nicotinic receptors to release more acetylcholine in the brain. Nicotinic acetylcholine receptors may represent an effective target for the treatment of AD. Numerous studies, using a variety of research animals, have demonstrated improvement in working memory with both short-term and long-term nicotine administration, and impairment of working memory using nicotine antagonists (White and Levin, 1999) In the studies by Sahakian and Jones (1991), Nicotine administration by subcutaneous injection has been shown to improve attention-related tasks in Alzheimer’s disease subjects. Another group of investigators found some evidence of improved memory with intravenous nicotine injection in AD subjects (Newhouse et al. 1988). However, the study did not detect significant chronic nicotine- induced effects on memory in Alzheimer’s disease patients. Possibly, the high peak achieved by acute injection of nicotine is necessary to produce memory improvement in Alzheimer’s disease patients (White and Levin, 1999) Furthermore, a study by Fujii and colleagues (Fujii et al, 2000) examined the modulatory effect of nicotine on the induction of **long-term potentiation (LTP)**, a synaptic model of learning and memory. These investigators showed that nicotine was able to promote the induction of LTP, apparently by reversing inhibitory postsynaptic potentials produced in the presence of a GABA receptor agonist. Intriguingly, this effect was also seen with the a7 nicotinic antagonist methyllycaconitine, suggesting that nicotinic receptor inactivation or blockade may have been involved in producing the positive effect of LTP (Newhouse, et al, 2001). **Moderate/Severe AD:** **Namenda (memantine)** regulates glutamate in the brain, which plays a key role in processing information. Namenda is an N-methyl D-aspartate (NMDA) antagonist that regulates the activity of glutamate in the brain. Glutamate plays a key role in memory and learning, but excess glutamate can lead to the disruption of nerve cell communication or nerve cell death. A dysfunction of glutamatergic neurotransmission is thought to be involved in the etiology of AD. **New Treatment** A molecule designed by a PurdueUniversity researcher to stop the debilitating symptoms of AD has been shown in its first phase of clinical trials to be safe and to reduce biomarkers for the disease. The molecule, called a **beta-secretase inhibitor**, prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. This plaque formation creates fibrous clumps of toxic proteins that are believed to cause the devastating symptoms of Alzheimer's. **Medicinal Plants and Natural Products** As there are negative side effects of the above mentioned drugs, such as nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia, and the cause of AD is still under investigation, there are many other medicinal plants and natural products being tested for curing AD (Butterfielda, 2002). **Galanthamine** Alzheimer patients can be treated with a class of drug called acetylcholinesterase inhibitors which slow the progression of the disease and alleviate many of the symptoms. One such compound is galanthamine, which is an alkaloid found in plants such as daffodils and snowdrops ( Morris and Nash, 2007).

Welsh Treatment for Alzheimers Disease [0:45-5:33] media type="youtube" key="hoGhqYN68i8" height="315" width="420" Curcumin also has a potential role in the prevention and treatment of AD. Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD. Due to various effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation, the overall memory in patients with AD has improved (Suri, 2003).
 * Curcumin**

咖喱防 ** 老 ** 人痴呆 ** 症 ** [0:00-.1:07] media type="youtube" key="BmEshLxIbY4" height="315" width="420"

There are various drugs authorized and tested for the treatment of AD, still there are many candidate drugs fail in clinical trials. According to the consensus emerging from the Alzheimer's Association International Conference in Paris (July 2011), drugs fail because they are given too late, after the accumulation of amyloid-β peptides, which form sticky plaques in the brain, and other physiological changes have already destroyed the patient's neurons and neuronal networks. At that point, even removing the amyloid-β, the aim of many of the treatments will not be effectively achieved and the need for further research in this area is still extensive. Besides, concerns about the side effects also drew much attention to caregivers a more balanced way to treating the AD pateint. (Tabel below shows the side effects of popular AD drugs) Research findings: in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal
 * Exercise training increases size of hippocampus and improves memory**

volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. (Erickson, et al, 2010)
The literature of the emerging field of cognitive rehabilitation described the impact of memory training for the early stage of AD patient. One encouraging report in the literature is of an eight-month experimental cognitive stimulation program involving 10 early Alzheimer patients and their spouses and six control couples that was sponsored by the University of San Diego. The caregivers were trained to provide one hour a day of activities from three different categories: conversation, memory stimulating exercises, and problem solving techniques. Monthly "booster" sessions were provided by project staff at the couples' homes. Results showed that patients in the program maintained theirlevels ofcognitive and behavioral functioning, while the control patients deteriorated. (Arkin, 1991)
 * <span style="font-family: Arial,Helvetica,sans-serif;">Memory training in early Alzheimer's disease **

The caregivers of AD patients are generally under lots of stress that are intensified by their limited knowledge, skills and experience, thus the AD patients may not be properly taken care of and their cognitive impairment may be even worsened. Participation in the Memory Club which incorporated group activities involving AD patients and caregivers also appeared to improve care partners’ perceptions of effectiveness when dealing with and managing various tasks related to memory loss. Specifically, care partners reported greater confidence in dealing with the various mood problems, memory concerns, and daily tasks that many PWMLs may struggle with (or begin to struggle with) during the early stages of dementia. The results suggest that the Memory Club can fill an important gap in early-stage dementia care by offering care partners the opportunity to plan, prepare, and increase coping skills in the face of early dementia progression. (Gaugler, 2011)
 * Social interaction merging memory exercise for AD patient caregivers**

Although there are quite a number of clinical tested drugs available for the AD, the psychological intervention in the form of phyical execise, memory training, social intercation and coping skills is considered to be quite essential in supplementing the positive effect of frugs for AD patients. There are coping skills like enhancing AD patient's capability to maintain their independency, simplifying daily task, e.g. cloths easily to put on, separating daily tools, coping with their daily habits and using environmental cues e.g. signages.
 * Treatment incorporating medication and coping skills**

老年癡呆症照顧篇(二) 中度至嚴重程度 學習照顧技巧 [ 2:09 - 4:54 ]

media type="youtube" key="mActlJqy8DI" height="315" width="420" Social support from community [1:56 - 2:30]

Different types of treatment, e.g. art treatment, music treatment, multi-sensory treatment [3:17 - 4:00] media type="youtube" key="aXdAiji0EtU" height="315" width="420" <span style="color: #4c4c4c; font-family: 'Verdana','sans-serif'; font-size: 12px;">Furthermore, research found that group therapy benefits AD patients as it reduces stigmatization, increase social support amongst patients and, more important, patients can learn from each other during the therapy (Leszcz, 2011).
 * Conclusion**

<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">AD is incurable and AD patients’ cognitive functions deteriorate as the disease progresses. Although the cause of this disease is still unknown, efforts have been made by medical researchers to invent or develop new treatment or medicine in order to decrease the speed of deterioration. Early diagnosis is helpful as early treatment would help slower the speed of degeneration and eliminate negative impact of the disease. From social perspective, support from family and society is very important as this would help AD patients minimize their feeling of helplessness on this uncontrollable disease.


 * <span style="font-family: Arial,Helvetica,sans-serif;">References **

<span style="display: block; height: 1px; left: 0px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: -25px; width: 1px;"> 1 Long Term Potentiation introduction [Video file]. Retrieved from [] Alzheimer’s Association. (2011). //Basics of Alzheimer’s disease: what it is and what you can do//. Retrieved from [] Alzheimer’s Disease - Environment, Lifestyle, Diet and Exercise (5 of 5) [Video file]. Retrieved from [] Bliss, T. V. P., Collingridge, G. L., & Morris, R. (2004). //Long-term potentiation: enhancing neuroscience for 30 years//. Oxford: Oxford University Press. Butterfielda, D.A., Castegnaa, A., Pocernicha, C.B., Scapagninib, J.D.G., Calabresec, V. (2002). Nutritional approaches to combat oxidative stress in Alzheimer’s disease. //Journal of Nutritional Biochemistry.// 13, 444-461. Carlson, N.R. (2011). //Foundations of behavioral neuroscience// (8th ed.). Boston: Allyn & Bacon. Cyranoski, D. (July 22, 2011). Alzheimer's disease genes aid the search for preventive drugs. //International Weekly Journal of Science//. Retrieved November 19, 2011 from [] Development of NIC5-15 in the Treatment of Alzheimer's Disease. (2010). Retrieved November 19, 2011 from U.S. National Institutes of Health. Web site: [] Dhikav, V., & Anand, K. (2011). Potential predictors of hippocampal atrophy in Alzheimer’s disease. //Drugs and Aging, 28,// 1, 1-11. Dickerson, B. C., & Eichenbaum, H. (2010). The episodic memory system: Neurocircuitry and disorders. //Neuropsychopharmacology, 35,// 1, 86-104. Forstl, H. & Kurz, A. (1999). Clinical features of Alzheimer's disease//. European Archives of Psychiatry and Clinical Neuroscience, 249// (6), 288-290. General information (2010). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer's Disease Education & Referral Center Web site: [] Gerrig, R. J., & Zimbardo, P. G. (2008). //Psychology and life// (18th ed.). Boston: Allyn & Bacon. Graham, K. S., & Hodges, J. R. (1997). Differentiating the roles of the hippocampus complex and the neocortex in long-term memory storage: Evidence from the study of semantic dementia and Alzheimer’s disease. //Neuropsychology, 11//(1), 77-89. doi:10.1037/0894-4105.11.1.77 Greenberg, D. L., Keane, M. M., Ryan, L., & Verfaellie, M. (2009). Impaired category fluency in medial temporal lobe amnesia: the role of episodic memory. //The Journal of Neuroscience,// 29(35), 10900-10908. doi: 10.1523/JNEUROSCI,1202-09.2009 Hill, C. (Aug 03, 2008). Retrieved November 19, 2011 from About.com Guide. Alzheimer's Treatment Medications and Approaches Used in the Treatment of Alzheimer's Disease. Web site: [] Hunt, R. R., & Ellis, H. C. (2004). //Fundamentals of cognitive psychology// (7th ed.). Boston: McGraw-Hill. Inside the Brain: Unraveling the Mystery of Alzheimer’s Disease [HQ] [Video file]. Retrieved from [] Jelicic, M., Bonebakker, A. & Bonke, B. (1995). Implicit memory performance of patients with Alzheimer's disease: A brief review//. International Psychogeriatrics, 7// (3), 385-392. Kalat, J. W. (2009). //Biological Psychology// (10th ed.). Belmont, CA: Wadsworth, Cengage Learning. Kertesz, A. & Kertesz, M. (1988). Memory deficit and language dissolution in Alzheimer's disease//. Journal of Neurolinguistics, 3// (1), 103-114. L Cerasoli. “Life with Alzheimer's" Presents... TRUTH [Video file]. Retrieved from [|http://www.youtube.com/watch?v=xDvvMpuJFsw&feature=player_embedded#] Lewis, D. J. (1979). Psychobiology of active and inactive memory. //Psychological Bulletin, 86//(5), 1054-1083. doi:10.1037/0033-2909.86.5.1054 Medicine discussed in this guide. (Jan 04, 2011). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer’s Disease Education and Referral Centre. Web site: [] Morris, P. and Nash, R. (2007). Natural products and feedstocks from plants. IGER Innovations. Retrieved from [] Nader, K., & Hardt, O. (2009). A single standard for memory: The case for reconsolidation. //Nature Reviews Neuroscience, 10,// 3, 224-234. Newhouse, P.A., Potter, A., Kelton, M., Corwin, J. (2001). Nicotinic Treatment of Alzheimer’s Disease. //Biol Psychiatry//. 49:268-278. Newman, E. L., Caplan, J. B., Kirschen, M. P., Korolev, I. O., Sekuler, R., & Kahana, M. J. (2007). Learning your way around town: how virtual taxicab drivers learn to use both layout and landmark information. //Cognition,// 104(2), 231-253. Niedermeyer, E., & Ghigo, J. O. (2011). Alzheimer dementia: an overview and a promising new concept. //American Journal of Electroneurodiagnostic Technology, 51,// 2, 82-91. Ohno, M. (2009). Failures to reconsolidate memory in a mouse model of Alzheimer’s disease. //Neurobiology of Learning and Memory, 92//(3), 455-459. doi:10.1016/j.nlm.2009.05.001 Sperling, R. A., Dickerson, B. C, Pihlajamaki, M., Vannini, P., LaViolette, P. S., Vitolo, O. V., … Johnson, K. A. (2010). Functional alterations in memory networks in early Alzheimer’s disease. //Neuromolecular Medicine//, 12(1), 27-43. doi: 10.1007/s12017-009-8109-7 Suri A.A. (2003). The anti-oxidative effects of curcumin on memory curves of planaria: A model for the treatment of Alzheimer's disease. p. S1425. Retrieved from [] The Hallmarks of AD (2011). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzhimer's Disease Education & Referral Center Web site: [] Tiraboschi, P., Hansen, L.A., Thal, L. J. & Corey-Bloom, J. (2004). The importance of neuritic plaques and tangles to the development and evolution of AD. //Neurology, 62// (11), 1984-9. Treating Alzheimer's Disease (Alzheimers #3) [Video file] Retrieved from [] Understanding stages and symptoms of Alzheimer's disease (2009). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer's Disease Education & Referral Center Web site: [] Wang, S. H., Teixeira, C. M., Wheeler, A. L., & Frankland, P.W. (2009). The precision of remote context memories does not require the hippocampus//. Nature Neuroscience, 12// (3), 253-255. doi:10.1038/nn.2263 Welsh Treatment for Alzheimers Disease [Video file] Retrieved from [] Whalley, K. (2009). Learning and memory: Past times//. Nature Reviews Neuroscience, 10// (3), 170-171. White, H. K. and Levin, E.D. (1999). Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. //Psychopharmacology//. 143 : 158-165. 老年癡呆症照顧篇 [Video file]. Retrieved from [] 老年癡呆症照顧篇 ( 二 ) 中度至嚴重程度 [Video file]. Retrieved from [] 咖喱防 ** 老 ** 人痴呆 ** 症 ** [Video file]. Retrieved from [] 1 Long Term Potentiation introduction [Video file]. Retrieved from []

Akin, S.M. (1991).Memory training in early Alzheimer's disease: An optimistic look at the field. American Journal of Alzheimer's Disease and Other Dementias. Retrieved from []

Alzheimer’s Association. (2011). //Basics of Alzheimer’s disease: what it is and what you can do//. Retrieved from []

Alzheimer’s Disease - Environment, Lifestyle, Diet and Exercise (5 of 5) [Video file]. Retrieved from [] Alzheimer’s Disease Medications fact Sheet. Retrieved from []

Bliss, T. V. P., Collingridge, G. L., & Morris, R. (2004). //Long-term potentiation: enhancing neuroscience for 30 years//. Oxford: Oxford University Press.

Butterfielda, D.A., Castegnaa, A., Pocernicha, C.B., Scapagninib, J.D.G., Calabresec, V. (2002). Nutritional approaches to combat oxidative stress in Alzheimer’s disease. //Journal of Nutritional Biochemistry.// 13, 444-461.

Carlson, N.R. (2011). //Foundations of behavioral neuroscience// (8th ed.). Boston: Allyn & Bacon.

Cyranoski, D. (July 22, 2011). Alzheimer's disease genes aid the search for preventive drugs. //International Weekly Journal of Science//. Retrieved November 19, 2011 from []

Development of NIC5-15 in the Treatment of Alzheimer's Disease. (2010). Retrieved November 19, 2011 from U.S. National Institutes of Health. Web site: []

Dhikav, V., & Anand, K. (2011). Potential predictors of hippocampal atrophy in Alzheimer’s disease. //Drugs and Aging, 28,// 1, 1-11.

Dickerson, B. C., & Eichenbaum, H. (2010). The episodic memory system: Neurocircuitry and disorders. //Neuropsychopharmacology, 35,// 1, 86-104. Erickson, K. I. (2010).Exercise training increases size of hippocampus and improves memory. Retrieved from [|www.pnas.org/cgi/doi/10.1073/pnas.1015950108]

Forstl, H. & Kurz, A. (1999). Clinical features of Alzheimer's disease//. European Archives of Psychiatry and Clinical Neuroscience, 249// (6), 288-290.

Gaugler, J. E. et al (2011). The Memory Club: Providing Support to Persons with Early-Stage Dementia and Their Care Partners. //American Journal of Alzheimer’s// //Disease & Other Dementias.// Retrieved from []

Gallagher, D., Mhaolain, A.N., Crosby, L, Ryan, D., Lacey, L., Coen, R.F., Walsh, C., Coakley, D., Walsh, J. B., Cunningham, C. & Lawlor, B.A. (2011). Self-efficacy for managing dementia may protect against burden and depression in Alzheimer's caregivers. // Aging & Mental Health, 15, // 6, 663-70. DOI: 10.1080/13607863.2011.562179

General information (2010). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer's Disease Education & Referral Center Web site: []

Gerrig, R. J., & Zimbardo, P. G. (2008). //Psychology and life// (18th ed.). Boston: Allyn & Bacon.

Graham, K. S., & Hodges, J. R. (1997). Differentiating the roles of the hippocampus complex and the neocortex in long-term memory storage: Evidence from the study of semantic dementia and Alzheimer’s disease. //Neuropsychology, 11//(1), 77-89. doi:10.1037/0894-4105.11.1.77

Greenberg, D. L., Keane, M. M., Ryan, L., & Verfaellie, M. (2009). Impaired category fluency in medial temporal lobe amnesia: the role of episodic memory. //The Journal of Neuroscience,// 29(35), 10900-10908. doi: 10.1523/JNEUROSCI,1202-09.2009

Hill, C. (Aug 03, 2008). Retrieved November 19, 2011 from About.com Guide. Alzheimer's Treatment Medications and Approaches Used in the Treatment of Alzheimer's Disease. Web site: []

Hunt, R. R., & Ellis, H. C. (2004). //Fundamentals of cognitive psychology// (7th ed.). Boston: McGraw-Hill.

Inside the Brain: Unraveling the Mystery of Alzheimer’s Disease [HQ] [Video file]. Retrieved from []

Jelicic, M., Bonebakker, A. & Bonke, B. (1995). Implicit memory performance of patients with Alzheimer's disease: A brief review//. International Psychogeriatrics, 7// (3), 385-392.

Hippocampal atrophy [Image]. Retrieved November 21, 2011, from: []

Kalat, J. W. (2009). //Biological Psychology// (10th ed.). Belmont, CA: Wadsworth, Cengage Learning.

Kertesz, A. & Kertesz, M. (1988). Memory deficit and language dissolution in Alzheimer's disease//. Journal of Neurolinguistics, 3// (1), 103-114.

L Cerasoli. “Life with Alzheimer's" Presents... TRUTH [Video file]. Retrieved from [|http://www.youtube.com/watch?v=xDvvMpuJFsw&feature=player_embedded#]

<span style="color: #000000; font-family: Arial,Helvetica,sans-serif; font-size: 100%;">Leszcz, M. (2011). Review of "multisensory stimulation for elderly with dementia: A 24-week single-blind randomized controlled pilot study" and "A cognitive behavioral group therapy for patients diagnosed with mild cognitive impairment and their significant others: Feasibility and preliminary results.". //International Journal of Group Psychotherapy, 61//(1), 153-158. Retrieved from http://search.proquest.com/docview/854376267?accountid=16210

Lewis, D. J. (1979). Psychobiology of active and inactive memory. //Psychological Bulletin, 86//(5), 1054-1083. doi:10.1037/0033-2909.86.5.1054

Majid Fotuhi. //Changing Perspectives Regarding Aging and Alzheimer’s Disease// [PowerPoint slides]. Retrieved from []

Medicine discussed in this guide. (Jan 04, 2011). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer’s Disease Education and Referral Centre. Web site: []

Morris, P. and Nash, R. (2007). Natural products and feedstocks from plants. IGER Innovations. Retrieved from []

Nader, K., & Hardt, O. (2009). A single standard for memory: The case for reconsolidation. //Nature Reviews Neuroscience, 10,// 3, 224-234.

Newhouse, P.A., Potter, A., Kelton, M., Corwin, J. (2001). Nicotinic Treatment of Alzheimer’s Disease. //Biol Psychiatry//. 49:268-278.

Newman, E. L., Caplan, J. B., Kirschen, M. P., Korolev, I. O., Sekuler, R., & Kahana, M. J. (2007). Learning your way around town: how virtual taxicab drivers learn to use both layout and landmark information. //Cognition,// 104(2), 231-253.

Niedermeyer, E., & Ghigo, J. O. (2011). Alzheimer dementia: an overview and a promising new concept. //American Journal of Electroneurodiagnostic Technology, 51,// 2, 82-91.

Ohno, M. (2009). Failures to reconsolidate memory in a mouse model of Alzheimer’s disease. //Neurobiology of Learning and Memory, 92//(3), 455-459. doi:10.1016/j.nlm.2009.05.001

Sperling, R. A., Dickerson, B. C, Pihlajamaki, M., Vannini, P., LaViolette, P. S., Vitolo, O. V., … Johnson, K. A. (2010). Functional alterations in memory networks in early Alzheimer’s disease. //Neuromolecular Medicine//, 12(1), 27-43. doi: 10.1007/s12017-009-8109-7

Suri A.A. (2003). The anti-oxidative effects of curcumin on memory curves of planaria: A model for the treatment of Alzheimer's disease. p. S1425. Retrieved from [] The changing brain in AD (2011). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzhimer's Disease Education & Referral Center Web site: []

The hallmarks of AD (2011). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzhimer's Disease Education & Referral Center Web site: []

Tiraboschi, P., Hansen, L.A., Thal, L. J. & Corey-Bloom, J. (2004). The importance of neuritic plaques and tangles to the development and evolution of AD. //Neurology, 62// (11), 1984-9.

Treating Alzheimer's Disease (Alzheimers #3) [Video file] Retrieved from []

Understanding stages and symptoms of Alzheimer's disease (2009). Retrieved November 19, 2011 from U.S. National Institutes of Health, Alzheimer's Disease Education & Referral Center Web site: []

Wang, S. H., Teixeira, C. M., Wheeler, A. L., & Frankland, P.W. (2009). The precision of remote context memories does not require the hippocampus//. Nature Neuroscience, 12// (3), 253-255. doi:10.1038/nn.2263

Welsh Treatment for Alzheimers Disease [Video file] Retrieved from []

Whalley, K. (2009). Learning and memory: Past times//. Nature Reviews Neuroscience, 10// (3), 170-171.

White, H. K. and Levin, E.D. (1999). Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. //Psychopharmacology//. 143 : 158-165. <span style="font-family: '新細明體','serif'; font-size: 16px;">老年癡呆症 <span style="font-family: 'times new roman','serif'; font-size: 16px;">[ <span style="font-family: '新細明體','serif'; font-size: 16px;">腦退化症 <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">] [Video file]. Retrieved from []

<span style="font-family: '新細明體','serif'; font-size: 15px;">老年癡呆症照顧篇 [Video file]. Retrieved from []

<span style="font-family: '新細明體','serif'; font-size: 15px;">老年癡呆症照顧篇 ( <span style="font-family: '新細明體','serif'; font-size: 15px;">二 ) <span style="font-family: '新細明體','serif'; font-size: 15px;">中度至嚴重程度 [Video file]. Retrieved from []

<span style="font-family: '新細明體','serif'; font-size: 15px;">咖喱防**老**人痴呆**症** [Video file]. Retrieved from []

老年癡呆症照顧篇(二) 中度至嚴重程度 學習照顧技巧 [Video file]. Retrieved from []

=**香港老年痴呆症協會 [Video file]. Retrieved from **[]= = =