Dementia Case - Psychiatry
Content
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 21st 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.
Predisposing
factors
Precipitating
Biology
Family history
Alzheimer’s
disease
-
Psychology
of -
-
Social
-
-
factors
Perpetuating
factors
-
-
-
Preferred Diagnosis
DIAGNOSIS
Major
neurocognitive
disorder due to probable
Alzheimer’s
disease
without
behavioural
disturbances; currently of
mild-to-moderate severity
PROS
-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
CONS
-No
occasions
where
patient appeared to be
confused
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 disease1. 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 permeability2. 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 voltagedependent 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
strength2.
In Alzheimer’s disease, the pathological way of activating NMDA receptors is explained
using signal-to-noise ratio hypothesis4. 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 receptors5. 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 noise4. In turn, synaptic
noise rises and this impairs the signal detection (cognitive function) in postsynaptic
neurons4. 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 neurons5.
Memantine is also an uncompetitive NMDA antagonist like Mg2+, which functions to
suppress the noise4,5. 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 kinetics5. 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
receptors4; 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 20136. 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 study6 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 al6. 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 study6 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 study6 stated that a RCT by Doody et al found that memantine
use together with either donepezil 23mg or donepezil 10mg daily for moderate-tosevere 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 20077
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:
http://www.nice.org.uk/guidance/TA217/chapter/1-Guidance
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
http://www.chrisparsons.de/Chris/Acrobat/Danysz_2000_b.pdf
4. Wojciech Danysz and Chris G 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];
167(2):
324-352.
Available
from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481041/
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:
367-377. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762361/
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#
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 21st 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.
Predisposing
factors
Precipitating
Biology
Family history
Alzheimer’s
disease
-
Psychology
of -
-
Social
-
-
factors
Perpetuating
factors
-
-
-
Preferred Diagnosis
DIAGNOSIS
Major
neurocognitive
disorder due to probable
Alzheimer’s
disease
without
behavioural
disturbances; currently of
mild-to-moderate severity
PROS
-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
CONS
-No
occasions
where
patient appeared to be
confused
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 disease1. 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 permeability2. 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 voltagedependent 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
strength2.
In Alzheimer’s disease, the pathological way of activating NMDA receptors is explained
using signal-to-noise ratio hypothesis4. 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 receptors5. 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 noise4. In turn, synaptic
noise rises and this impairs the signal detection (cognitive function) in postsynaptic
neurons4. 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 neurons5.
Memantine is also an uncompetitive NMDA antagonist like Mg2+, which functions to
suppress the noise4,5. 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 kinetics5. 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
receptors4; 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 20136. 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 study6 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 al6. 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 study6 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 study6 stated that a RCT by Doody et al found that memantine
use together with either donepezil 23mg or donepezil 10mg daily for moderate-tosevere 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 20077
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:
http://www.nice.org.uk/guidance/TA217/chapter/1-Guidance
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
http://www.chrisparsons.de/Chris/Acrobat/Danysz_2000_b.pdf
4. Wojciech Danysz and Chris G 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];
167(2):
324-352.
Available
from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481041/
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:
367-377. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762361/
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#
