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PSYCHIATRIC HISTORY

Presenting Complaint

Mr T (I.C. xxxxxx-xx-5045) is a 73-year-old Chinese man, married with one son, currently unemployed, formerly worked as a hawker, living with his wife in Kampung Ara, Bayan Lepas who was brought to the psychogeriatric clinic by his wife for his second follow up on 21 st July 2014 due to Alzheimer’s disease as mentioned by his wife.

History of Presenting Complaints

It is mainly the collateral history from his wife, added with history from the patient himself.

Past 3-4 years ago, Mrs T, patient’s wife, first noticed problems with memory where she gave an example of him misplacing the bike or house keys and blaming her for that and this led to arguments. She noticed his memory continues to deteriorate over the 3-4 years and he becomes more forgetful. Thus he was brought to the neurology clinic by his wife as suggested by their family general practitioner when his wife told their family GP about the changes in his memory. The neurologist diagnosed him having Alzheimer’s disease. Since then they had follow up for a year with neurology clinic and he is on memantine since then. Patient reported no constipation. And currently, they were referred to psychogeriatric clinic. During their initial visit to psychogeriatric clinic, mental state examination was done and she was asked to continue her husband’s medications. Once he forgot to bring his mobile phone. At that time, he was unable to call her because he told her that he forgot her mobile phone number. She also claimed that once Mr T denied a friend came to their house when Mrs T was not at home. He also talks about the past- families, relatives, and son going to school, his work again and again even though she is not interested in listening to him. Recently, for the past few months, she claimed he forgets that he had his meal already. He keeps turning on and off the fan when they are sleeping and when Mrs T questions him, he tends to ignore her. She became more intolerable with Mr T when he showers every half an hour in the evening. She stuck a paper on the wall for Mr T to mark on the paper every time he goes to shower, however Mr T still denies that he does. She claimed that he does not have any reminders as she is the one who reminds him of any activities, for an example any family gathering. On the other hand, upon questioning Mr T, he did not acknowledge his memory problems and claimed that his wife insisted to bring him to see the doctor.

Furthermore, Mrs T noticed he was unable to recall the names of his close friends who he frequently meets. Otherwise she claimed he has no language difficulties, no words repetition and he can recall of the wife’s and son’s names.

She also told that he follows her to get to a new, unfamiliar place. Also to the hospital, she needs to navigate him as they come to hospital for follow up once every 2-3 months. She does not allow him to drive alone at night because she is afraid he will get stranded as he has problems with his memory, and she claimed that he listens to her. She claimed that there were no experiences that he got stranded, and Mr T agreed to the statement. She claimed that he only goes to the food stalls alone during the day. During the interview, she expressed her worries when Mr T got up and walked around. Otherwise, he can remember the direction to the wife’s office from their house and vice versa because he drives her to the workplace daily.

Mrs T claimed that even though she becomes irritated with his activities he seems not to understand how she feels. Otherwise, she never heard of his friends complaining that he shows insensitivity to sensitive topics of conversation.

Patient denied any problems with his attention. He claimed he is still able to perform mental calculation. He also denied normal tasks taking long than previously.

Mrs T controls family finance ever since they are married, so she is not sure whether he would make any gross errors in financial management. Mr T was unsure whether he has problems with planning, organizing or deciding as he does not have to plan, organize or decide. He claimed that he has no problem going for social gatherings. Mrs

T has been giving medications on time daily as he denies that he has illness thus she

does not know whether he can manage his medications alone.

Otherwise, she denied that he has any problems feeding, toileting, grooming, maintaining continence, bathing and walking. She also claimed he never went unconscious, never seen him too sad or too happy. Mr T denied that he has been too sad, has been too happy or felt anxious. He denied any suicidal thoughts. The wife claimed he became restless ever since he stopped working, thus she told him to help

carrying things in her office. Mrs T was unable to recall any occasions patient appeared

to be confused.

Mr T stopped working in the hawker stall as he claimed there were problems at work. Mrs T claimed that it was due to his memory problems, however she did not describe it further and Mr T denied it. He has multiple awakenings during sleep, however he is still able to sleep back and he denied difficulty initiating sleep. He claimed relationship with his wife and the others is good, however his wife claimed that she is getting intolerable with his activities. Both denied any changes in his appetite, self-care and energy. Mrs T also denied any history of head injuries for her husband.

Previous Psychiatric History

No previous episode of depression or other psychiatric illnesses.

History of Self-Harm

No history of self-harm attempt.

Previous Medical/ Surgical History

Patient has no medical illness, specifically hyperthyroidism and Parkinson’s disease, previous surgery or previous admission due to any medical illness.

Drug and Alcohol History

No drug or alcohol abuse.

Family Psychiatric History

Mrs T claimed that her husband’s father had Alzheimer’s disease, however Mr T denied it. He claimed that both of his parents passed away at old age due to no known reason. No family history of suicide or substance misuse.

Personal History

Childhood

During his childhood, he claimed he was happy. No history of trauma, neglect or sexual abuse. He has 3 siblings; he is the third. He was unsure how he was delivered or his developmental milestones.

School

He completed his primary school. He had a good relationship with his classmates and teachers. He obtained average grades in his school. He stopped schooling as he had no interest in studies. He used to play with his friends after school. However, he was unable to recall his close friends’ names. He had no experience of being bullied.

Work Record

He had a hawker stall in Jelutong Market. He used to be a partner in a restaurant business with his friend in Kuala Lumpur. He stopped being the business partner about 10 years ago. He was not sure why he stopped being the business partner.

Psychosexual History

He is married to wife for more than 30 years; this statement was agreed by his wife. He was unable to recall their anniversary date. He claimed it is a love marriage, however he cannot recall where they first met. He had no previous girlfriend or sexual experience outside marriage. He claimed his relationship with his wife and his only son is good.

Social History

He lives in a single-storey house Kampung Ara with his wife. His wife is working as a human resource officer in Lam Wah Ee Hospital and currently, supporting themselves. Their son is working in Kuala Lumpur. He has no religious affiliations.

Forensic History

No trouble with the law and no history of violence.

Premorbid Personality

His wife claimed he was a hardworking and friendly man.

CURRENT MENTAL STATE

General Appearance and Behaviour

Patient was alert, conscious, well kempt and noted to be restless. Patient was not interested in the conversation and guarded. He established a minimal rapport with on and off eye contact.

Form of Thought (Speech)

He spoke in Malay. Volume, rate and tone were appropriate, however amount was little. Speech was coherent and relevant. No flight of ideas and formal thought disorder.

Mood

Patient described his mood was normal and I observed his mood to be normal too.

Affect

Affect was normal, congruent with his mood.

Thought Content

He denied any delusions, thought broadcasting, thought insertion, thought withdrawal, feeling of passivity, depersonalization, derealiasation, preoccupations, obsessions and phobias. No suicidal or homicidal thoughts.

Perceptions

He denied having hallucinations and illusions.

Judgment

He had a good judgment as he said that he would call the fire brigade if there is fire at home.

Insight

He had a poor insight as he kept denying his illness and problems with his memory. He claimed that he comes to the follow up just because of his wife. He thinks that he does not need medications.

Mini Mental State Examination

Total score= 15/30 which is a definite cognitive impairment

Notes:

1. Recall was 0 for first attempt, then subsequently 1, 2, 2, and 2.

2. The sentence was dictated by his wife, so the score was 0.

3. He scored 4 for the clock-drawing test, which is not part of the MMSE score.

PHYSICAL EXAMINATION

He was alert, conscious and well-perfused. His pulse rate was 86 beats/min. Blood pressure was not taken. Cardiovascular, respiratory, gastrointestinal and neurological examinations were not done due to time constraint.

SUMMARY

Mr T, a 73-year-old Chinese man, an unemployed, married with a son presented to the clinic due to Alzheimer’s disease follow up as mentioned by his wife. He has gradual major cognitive decline in learning and memory domain, while gradual mild cognitive decline in language, perceptual-motor and social cognition domains. This is based on concern of his wife, a knowledgeable informant. MMSE score is 15. The cognitive decline interferes with independence in daily activities. However, his basic activities of daily living are not impaired and he has no other psychiatric or medical illnesses. He has no behavioural disturbances too.

 

Biology

Psychology

Social

Predisposing

Family

history

of

-

-

factors

Alzheimer’s

disease

Precipitating

-

-

-

factors

     

Perpetuating

-

-

-

factors

Preferred Diagnosis

 

DIAGNOSIS

 

PROS

CONS

Major

neurocognitive

-Gradual major cognitive decline in learning and memory domain -Gradual mild cognitive decline in language, perceptual-motor and social cognition domains Family history of Alzheimer’s disease - A substantial impairment in cognitive performance documented by MMSE score which is 15 -Based on concern of his wife, a knowledgeable informant -Cognitive deficits interfere with independence in daily activities e.g. He needs his wife to travel to unfamiliar places. -No behavioural disturbances

-No

occasions

where

disorder due to probable

patient appeared

to

be

Alzheimer’s

disease

confused

 

without

behavioural

 

disturbances;

currently

of

mild-to-moderate severity

MANAGEMENT

My further management is based on my provisional diagnosis which is major neurocognitive disorder due to probable Alzheimer’s disease with behavioural disturbances of mild-to-moderate severity. I would involve the multidisciplinary team in the management of this patient. I would try to involve the family/partner in the management in. I would plan the management according to biopscyhosocial model.

Investigations

Biology

Blood and urine for toxicology- to rule any substance abuse or toxicity

Fasting blood sugar- to assess as a risk factor for vascular disease

Fasting lipid profile- to assess as a risk factor for vascular disease

BUSE- to look for electrolyte imbalance

Serum B12 and folate- to look for deficiency

Thyroid function test- to rule out hypothyroidism

Serum calcium- to rule out hyperparathyroidism

Liver function test- to rule alcohol abuse

Renal profile- as a renal baseline

Chest X-ray- to look for any chest abnormalities

ECG- to assess cardiovascular abnormalities

FBC- to rule out infection and anemia

Mid-stream urine- to rule out delirium

Trace brain CT/MRI result- to look for any organic cause

Psychology

Geriatric Depression Scale- to look for depression in this patient

Cornell Scale for Depression in Dementia- to look for depression in this patient

Instrumental Activites of Daily Living (IADL) and Modified Barthel Index (basic ADL)

Treatment

Biology

I would first trace his old notes with the neurology department in Penang General to

look for his previous dosage of memantine and other drugs if any. I would continue with memantine if his previous records state that it is not suitable to give donepezil for him. Otherwise, if there is no such record, I would remove memantine and start him off with prescribe Donepezil (acetylcholinesterase inhibitor) 5mg daily at bedtime as recommended by NICE guidelines. After 1 month, I would increase the dose to 10mg if necessary.

I would provide information and discuss the benefits and common side effects of the

medication with her. Examples are diarrhea, muscle cramps, fatigue, nausea, vomiting and insomnia.

Psychology

I would psychoeducate him and his wife the nature and course of his illness- explain

that it is a progressive degenerative disease and the medication is to slow down the progression.

I would encourage the patient a healthy lifestyle i.e. exercise and healthy diet.

I would encourage him to keep his brain stimulated by doing problem solving, “Sudoku”, playing board game and doing recreational activities.

I would advise patient to avoid places that have high risk of him fall.

I would advise him to write notes to himself, so that he will not blame others.

I would also advise him to keep clock and calendar in his room to keep himself orientated.

I would also advise him to write his will if he has any properties and he is planning to pass them down to anyone.

I would suggest him:

-Reminiscence therapy to help him live through past experiences. E.g. Showing photographs of family holidays.

-Art therapy to provide meaningful stimulation, improve social interaction and improve levels of self-esteem.

-Music therapy to improve social interaction, increase levels of well-being and improve autobiographical memory.

-Massage and aromatherapy for relaxation to increase levels of well-being.

Social

I would help him deal with the defective ego functions such as keeping calendars for

orientation problems, making schedules to help structure activities and taking notes for memory problems.

I would give support to his wife as she is taking care of him - help her understand the complex mixture of feelings associated with seeing a loved one decline and provide understanding as well as permission to express such feelings.

I would give him opportunity to participate in a structured group cognitive stimulation program.

- Alzheimer’s Disease Foundation Malaysia (ADFM), Alzheimer Disease Penang support group

- Penang Care (Senior Citizen Day Care and Adult Depression Support Group) if he gets depressed or if wife has trouble taking care of him.

DISCUSSION

As biological management of Alzheimer’s disease, memantine is recommended as an option in NICE guidelines to manage people with moderate Alzheimer’s disease who are not tolerant of or have a contraindication to acetylcholinesterase inhibitors, or people with severe Alzheimer’s disease 1 . I would like to further talk about how memantine works and how evident base it is in managing patients with Alzheimer’s disease.

In order to know how memantine works, the mechanism of action of NMDA receptors must be understood. N-Methyl-D-Aspartate (NMDA) receptors are ionotropic glutamate receptors with high calcium permeability 2 . Physiologically, NMDA receptors are transiently activated by mM concentration of glutamate after postsynaptic neuron being depolarized with sufficient amplitude and duration which quickly relieves their voltage- dependent blockade by Mg2+ 3 . This allows the flow of permeant ions, Ca2+ 2 . This transduces specific synaptic input patterns into long-lasting alterations in synaptic strength 2 .

In Alzheimer’s disease, the pathological way of activating NMDA receptors is explained using signal-to-noise ratio hypothesis 4 . Beta-amyloid plaques, a pathological feature of Alzheimer’s disease can cause depolarization of astrocytes, extracellular accumulation of glutamate and intracellular deposition of Ca2+ 5 . Pathways of metabolizing the glutamate by neigbouring cells are disrupted in this pathological condition, thus the buildup of glutamate overexcites NMDA receptors 5 . In this situation, Mg2+ (NMDA antagonist) which normally filters the noise leaves the channel when it is supposed to stay in NMDA receptor’s pore, thus unable to suppress the noise 4 . In turn, synaptic noise rises and this impairs the signal detection (cognitive function) in postsynaptic neurons 4 . Thus synaptic plasticity (learning) could not take place 4 . This is followed by unrestricted calcium influx for longer period which alters the cell function and eventually damages the neurons 5 .

Memantine is also an uncompetitive NMDA antagonist like Mg2+, which functions to suppress the noise 4,5 . Both memantine and Mg2+ are able to leave the NMDA receptor channel upon strong synaptic depolarization due to their significant voltage dependency and rapid unblocking kinetics 5 . However memantine is more effective than Mg2+. Memantine stays in the channel during moderate prolonged depolarization during chronic excitotoxic insults caused by B-amyloid peptides tonically activating NMDA receptors 4 ; whereas Mg2+ would leave during chronic excitotoxic insults. As memantine could replace the function of Mg2t as an efficient blockade and it is more voltage

dependent than Mg2+, thus it works better than Mg2+ and it emerges as an invention to Alzheimer’s disease.

In the clinical setting, memantine’s benefits either alone or in combination with donepezil in moderate-severe Alzheimer’s disease were shown in a review of clinical trials done by Molino et al. in 2013 6 . For memantine monotherapy, the team chose 6 RCTs (randomized controlled trials) which were done in the European countries with mean age 74-86 and mean baseline MMSE 7-19. It was found that memantine enhanced global cognition and functional communication and had positive effect on some behavioural symptoms such as agitation, aggression and psychosis. This effect was shown in patients over 6 months taking memantine and it is significantly greater than that found in patients treated with placebo. However, the same study 6 stated that a RCT by Fox et al did not prove the effect of memantine on agitation.

In term of memantine and donepezil combination therapy, 2 clinical trials were reviewed in the study done by Molino et al 6 . The studies were done in countries in Asia, Europe, Australia, North America, South Africa and South America with mean age 74 and 77, and mean baseline MMSE 9 and 14. It was found that the memantine 20mg/day in combination with acetylcholinesterase inhibitor was well tolerated in moderate-to-severe Alzheimer’s disease patients. The study 6 stated a RCT by Howard et al showed that the cognitive benefits of the combination treatment exceed the minimal clinically important difference and the functional benefits are seen in 12 subsequent months. However, the team found that the combination has no significant benefits over donepezil alone. On the other hand, the same study 6 stated that a RCT by Doody et al found that memantine use together with either donepezil 23mg or donepezil 10mg daily for moderate-to- severe Alzheimer’s disease patients did not change the outcome of donepezil 23mg versus 10mg daily.

It can be concluded that memantine can improve the cognitive and communicative functions, as well as can contribute some effects on behavioural symptoms, and the benefits of memantine-donepezil combination therapy are equivalent to the benefits of donepezil alone. On the other hand, there is a study done by Pomara et al. in 2007 7 found that the benefits of memantine can be seen in core aspects of language and some aspects of memory in patients with mild-to-moderate Alzheimer’s disease. Thus, my patient with mild-to-moderate Alzheimer’s disease can still obtain benefits from memantine. However, it is best to avoid giving memantine as donepezil or any acetylcholinesterase inhibitors to be given to patients with mild-to-moderate Alzheimer’s disease as recommended in NICE guidelines.

REFERENCES

1. National Institute for Health and Care Excellence [Internet]. London: National Institute for Health and Care Excellence; c2014. Donepezil, galantamine,

rivastigmine and memantine for the treatment of Alzheimer’s disease; 2011 March [cited 2014 August 11]; [about 1 screen]. Available from:

2. Marie L. Blanke, and Antonius M.J. VanDongen. Medline Plus [Internet]. Bethesda (MD): U.S. National Library of Medicine; c2009. Chapter 13 Activation Mechanisms of the NMDA Receptor; 2009 [cited 2014 August 11]; [about 1 screen]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK5274/

3. Wojciech Danysz et al. Neuroprotetive and symptomatological action of memantine relevant for Alzheimer’s disease A unified glutamatergic hypothesis on the mechanism of action. Neurotoxicity Research [Internet]. 1999 November 29 [cited 2014 August 11]; 2: 85-97. Available from

Parsons. Alzheimer’s disease, B-amyloid,

glutamate, NMDA receptors and memantine searching for the connections. British Journal of Pharmacology [Internet]. 2012 Sep [cited 2014 August 11];

from:

167(2):

4. Wojciech

Danysz

and

Chris

G

324-352.

Available

5. Stuart J Thomas, and George T Grossberg. Memantine: a review of studies into its safety and efficacy in treating Alzheimer’s disease and other dementias:

Clinical Interventions in Aging [Internet]. 2009 Oct 12 [cited 2014 August 11]; 4:

6. Ivana Molino et al. Efficacy of Memantine’ donepezil, or their association in moderate-severe Alzheimer’s disease: A review of clinical trials: Scientific World Journal [Internet]. 2013 Oct 29 [cited 2014 August 11]; 2013: 925702. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830825/

7. Pomara N, Ott BR, Peskind E, and Resnick EM. Memantine treatment of cognitive symptoms in mild to moderate Alzheimer disease: secondary analyses from a placebo-controlled randomized trial: Alzheimer’s Disease Association Disorder Journal [Internet]. 2007 Jan-Mar [cited 2014 August 11]; 21(1): 60-4. Available from http://www.ncbi.nlm.nih.gov/pubmed/17334274#