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CASE PRESENTATION Dr. LU, QINCHI Dr. LU, QINCHI DEPARTMENT OF NEUROLOGY DEPARTMENT OF NEUROLOGY REN JI HOSPITAL REN JI HOSPITAL SHANGHAI JIAO TONG UNIVERSITY.

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Presentation on theme: "CASE PRESENTATION Dr. LU, QINCHI Dr. LU, QINCHI DEPARTMENT OF NEUROLOGY DEPARTMENT OF NEUROLOGY REN JI HOSPITAL REN JI HOSPITAL SHANGHAI JIAO TONG UNIVERSITY."— Presentation transcript:

1 CASE PRESENTATION Dr. LU, QINCHI Dr. LU, QINCHI DEPARTMENT OF NEUROLOGY DEPARTMENT OF NEUROLOGY REN JI HOSPITAL REN JI HOSPITAL SHANGHAI JIAO TONG UNIVERSITY SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE SCHOOL OF MEDICINE Tel: Tel:

2 History A 68-year-old woman has been noted by her daughter to have memory loss and confusion. The daughter states that her mother has been going “ downhill ” for the past several months. The mother has lived on her own for many years,but recently she has begun to become unable to take care of herself. A 68-year-old woman has been noted by her daughter to have memory loss and confusion. The daughter states that her mother has been going “ downhill ” for the past several months. The mother has lived on her own for many years,but recently she has begun to become unable to take care of herself.

3 History The daughter states that her mother has become withdrawn and has lost interest in her usual activities, such as gardening and reading. Her mother ’ s memory is poor, and she is often fatigued. The patient states that she sleeps well at night and that her appetite is good, although she has lost 10 lb over the past 6 months. She denies bowel and urinary incontinence. The daughter states that her mother has become withdrawn and has lost interest in her usual activities, such as gardening and reading. Her mother ’ s memory is poor, and she is often fatigued. The patient states that she sleeps well at night and that her appetite is good, although she has lost 10 lb over the past 6 months. She denies bowel and urinary incontinence.

4 History The patient ’ s past medical history is significant for hypertension for which she has been taking hydrochlorethiazide. The patient was last hospitalized 35 years ago when she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The patient has enjoyed overall good health. She does not smoke or drink. The patient ’ s past medical history is significant for hypertension for which she has been taking hydrochlorethiazide. The patient was last hospitalized 35 years ago when she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The patient has enjoyed overall good health. She does not smoke or drink.

5 Physical Exam On examination, her blood pressure is 116/56 mmHg, her heart rate is 78 bpm, her temperature is 37.5 。 C, and her respiratory rate is 18 breaths per minute. She weighs 88 kg and her height is 1.62m. The patient is a well- developed white women with a flat affect. She is oriented to person, but she is not oriented to time and place. On examination, her blood pressure is 116/56 mmHg, her heart rate is 78 bpm, her temperature is 37.5 。 C, and her respiratory rate is 18 breaths per minute. She weighs 88 kg and her height is 1.62m. The patient is a well- developed white women with a flat affect. She is oriented to person, but she is not oriented to time and place.

6 Pyhsical & Neuro Exam Mini Mental Status Examination gives a score of 18 out of 30. The head and neck and cardiovascular examination are unremarkable. Abdomen is benign without hepatosplenomegaly. The extremities are without edema, cyanosis, or clubbing. The neurologic examination reveals that the cranial nerves are intact, and the motor and sensory exams are within normal limits. Cerebellum examination is unremarkable and the gait is normal. Mini Mental Status Examination gives a score of 18 out of 30. The head and neck and cardiovascular examination are unremarkable. Abdomen is benign without hepatosplenomegaly. The extremities are without edema, cyanosis, or clubbing. The neurologic examination reveals that the cranial nerves are intact, and the motor and sensory exams are within normal limits. Cerebellum examination is unremarkable and the gait is normal.

7 Questions What is the most likely diagnosis? What is the most likely diagnosis? What are the next diagnostic steps? What are the next diagnostic steps? What is the best treatment for this condition? What is the best treatment for this condition?

8 Summary: A 68-year-old woman has memory loss, confusion, and fatigue, and is withdrawn. She had a flat affect. She is oriented to person, but she is not oriented to time and place. The remainder of the examination, including neurological examination, is normal except for a low score on the MMSE. A 68-year-old woman has memory loss, confusion, and fatigue, and is withdrawn. She had a flat affect. She is oriented to person, but she is not oriented to time and place. The remainder of the examination, including neurological examination, is normal except for a low score on the MMSE.

9 Most likely diagnosis: Alzheimer dementia.

10 Next diagnostic step: Assess for depression and reversible causes of dementia. Assess for depression and reversible causes of dementia.

11 Probable treatment: Acetylcholinesterase inhibitor Acetylcholinesterase inhibitor

12 Analysis

13 Objectives Know some of the common causes of dementia Know some of the common causes of dementia Understand the presentation and diagnosis of Alzheimer dementia Understand the presentation and diagnosis of Alzheimer dementia Know the treatment for Alzheimer dementia is acetylcholinesterase inhibitor Know the treatment for Alzheimer dementia is acetylcholinesterase inhibitor

14 Considerations This is an elderly woman without any significant past medical history except for hypertension who was brought to your office with a history of progressive functional decline and memory loss. The first step should be to rule out depression. Depression in the elderly may have a presentation very similar to that of dementia with withdrawal, apathy, irritability, memory impairment, and confusion. This is an elderly woman without any significant past medical history except for hypertension who was brought to your office with a history of progressive functional decline and memory loss. The first step should be to rule out depression. Depression in the elderly may have a presentation very similar to that of dementia with withdrawal, apathy, irritability, memory impairment, and confusion.

15 Considerations The next step should be to rule out all the possible causes of reversible or arrestable dementia, such as multi-infarct dementia, hypothyroidism, drugs, B 12 deficiency, normal pressure hydrocephalus, alcoholism, HIV, and syphilis. The next step should be to rule out all the possible causes of reversible or arrestable dementia, such as multi-infarct dementia, hypothyroidism, drugs, B 12 deficiency, normal pressure hydrocephalus, alcoholism, HIV, and syphilis.

16 Considerations Laboratory tests will help you to eliminate some of these common causes of reversible dementia: complete blood count (CBC), comprehensive metabolic panel, thyroid- stimulating hormone (TSH), urinalysis, serologic test for syphilis, and a head CT (see table 49-1). Laboratory tests will help you to eliminate some of these common causes of reversible dementia: complete blood count (CBC), comprehensive metabolic panel, thyroid- stimulating hormone (TSH), urinalysis, serologic test for syphilis, and a head CT (see table 49-1).

17 Table 49-1 ABBREVIATED WORKUP FOR DEMENTIA Complete blood count and consider erythrocyte sedimentation rate (ESR) Chemistry panel Thyroid-stimulating hormone level Venereal Disease Research Laboratory (VDRL) HIV assay Urinalysis Serum vitamin B12 and folate levels Chest radiograph Electrocardiogram CT or MRI imaging of the head

18 Considerations The possibility of HIV-induced dementia is not high on the differential in this case given the patient ’ s age, but it would certainly be a consideration in younger people. Possible infectious causes of reversible dementia include not only HIV but also neurosyphilis. Therefore, a serologic test for syphilis is indicated. The possibility of HIV-induced dementia is not high on the differential in this case given the patient ’ s age, but it would certainly be a consideration in younger people. Possible infectious causes of reversible dementia include not only HIV but also neurosyphilis. Therefore, a serologic test for syphilis is indicated.

19 Considerations Because our patient does not have a history of chronic alcoholism, we can rule out this condition. The CBC and mean cell volume (MCV) are normal, as is the TSH, eliminating the possibilities of vitamin B 12 deficiency and of hypothyroidism. The patient is only taking hydrochlorothiazide, which is not associated with the described mental status changes. A CT head scan can assess for brain lesions, multiple infarcts, and hydrocephalus. Because our patient does not have a history of chronic alcoholism, we can rule out this condition. The CBC and mean cell volume (MCV) are normal, as is the TSH, eliminating the possibilities of vitamin B 12 deficiency and of hypothyroidism. The patient is only taking hydrochlorothiazide, which is not associated with the described mental status changes. A CT head scan can assess for brain lesions, multiple infarcts, and hydrocephalus.

20 Considerations Therefore, in this case we are left with the possibility of multi-infarct dementia and Alzheimer disease. Multi-infarct dementia develops later in life and is caused by diffuse cerebrovascular disease. Most of the patients will have a history of transient ischemic attacks and strokes, and stepwise progression of dementia which our patient does not report. In this particular case, Alzheimer dementia becomes the most likely diagnosis. Therefore, in this case we are left with the possibility of multi-infarct dementia and Alzheimer disease. Multi-infarct dementia develops later in life and is caused by diffuse cerebrovascular disease. Most of the patients will have a history of transient ischemic attacks and strokes, and stepwise progression of dementia which our patient does not report. In this particular case, Alzheimer dementia becomes the most likely diagnosis.

21 APPROACH TO DEMENTIA APPROACH TO DEMENTIA

22 Definitions Alzheimer disease: The leading cause of dementia, accounting for half of the cases involving elderly individuals, correlating to brain atrophy with ventricular enlargement. Alzheimer disease: The leading cause of dementia, accounting for half of the cases involving elderly individuals, correlating to brain atrophy with ventricular enlargement. Dementia: Progressive and generalized decline of intellectual ability from a previously attained level, usually without alteration of consciousness. Dementia: Progressive and generalized decline of intellectual ability from a previously attained level, usually without alteration of consciousness.

23 Definitions Multiinfarct dementia: Numerous small cerebral vascular accidents, most commonly caused by atherosclerotic disease, leading to dementia. Multiinfarct dementia: Numerous small cerebral vascular accidents, most commonly caused by atherosclerotic disease, leading to dementia. Normal pressure hydrocephalus: Reversible form of dementia where the cerebral ventricles slowly enlarge as a result of disturbances to cerebral spinal fluid resorption. The classic triad is dementia, gait disturbance, and urinary or bowel incontinence. Normal pressure hydrocephalus: Reversible form of dementia where the cerebral ventricles slowly enlarge as a result of disturbances to cerebral spinal fluid resorption. The classic triad is dementia, gait disturbance, and urinary or bowel incontinence.

24 Clinical Approach A patient who presents with memory and functional impairment should be approached from the perspective that many etiologies can be causative. A thorough description of the patient ’ s cognitive, adaptive, memory, and behavioral ability over time is critical. Multiple family members are often needed to construct a complete and accurate picture. The time frame (months to years versus days to weeks) is important. A patient who presents with memory and functional impairment should be approached from the perspective that many etiologies can be causative. A thorough description of the patient ’ s cognitive, adaptive, memory, and behavioral ability over time is critical. Multiple family members are often needed to construct a complete and accurate picture. The time frame (months to years versus days to weeks) is important.

25 Clinical Approach A history of head trauma, neurological symptoms, a stepwise decline (multi-infarct dementia) versus a insidious gradual decline may be helpful. A record of all medications, habits, alcohol use (even remote), can potentially cause mental status changes in the elderly. A resting tremor of Parkinson disease, cold intolerance suggestive of hypothyroidism, or vitamin deficiencies may be helpful. A history of head trauma, neurological symptoms, a stepwise decline (multi-infarct dementia) versus a insidious gradual decline may be helpful. A record of all medications, habits, alcohol use (even remote), can potentially cause mental status changes in the elderly. A resting tremor of Parkinson disease, cold intolerance suggestive of hypothyroidism, or vitamin deficiencies may be helpful.

26 Clinical Approach The other intracranial diseases that could cause a dementia-like picture include subdural hematoma and normal pressure hydrocephalus. Usually, a CAT (computed axial tomography) scan will allow you to rule out these disease processes. Also, remember, that normal pressure hydrocephalus is usually accompanied by gait disturbances and urinary incontinence which our patient does not have. The other intracranial diseases that could cause a dementia-like picture include subdural hematoma and normal pressure hydrocephalus. Usually, a CAT (computed axial tomography) scan will allow you to rule out these disease processes. Also, remember, that normal pressure hydrocephalus is usually accompanied by gait disturbances and urinary incontinence which our patient does not have.

27 Clinical Approach Parkinson disease is also associated with the development of dementia but patients with Parkinson disease have symptoms and physical findings that will alert you to the diagnosis. Table 49-2 lists the neurological diseases that impair cognitive ability. Parkinson disease is also associated with the development of dementia but patients with Parkinson disease have symptoms and physical findings that will alert you to the diagnosis. Table 49-2 lists the neurological diseases that impair cognitive ability.

28 Table 49-2 NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITY DISEASE CLINICAL FEATURES TREATMENT Alzheimer disease Slow decline in cognitive and behavioral ability; pathology: neurofibrillary tangles, enlarged cerebral ventricles, and atrophy Cholinesterase inhibitors such as donepezil or rivastigmine Normal-pressure hydrocephalus Gate disturbance, dementia, incontinence; enlarged ventricles without atrophy Ventricular shunting process Multi-infarct dementia Focal deficits, stepwise loss of function; multiple areas of infarct usually subcortical Address atherosclerotic risk factors, identify and treat thrombus Parkinson disease Extrapyramidal signs (tremor, rigidity), slow onset Dopaminergic agents

29 Table 49-2 (cont) NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITY DISEASE CLINICAL FEATURES TREATMENT HIV defintion Systemic involvement; risk factors for acquisition; positive HIV serology Treat specific infection Neurosyphilis Optic atrophy, Argyll-Robertson pupils, gait disturbance; positive cerebro-spinal fluid serology High dose intravenous penicillin Multiple sclerosis Brainstem signs, optic atrophy, long-standing disease with exacerbations and remissions; MRI showing white matter abnormalities Recombinant interferon, corticosteroids Intracranial tumor Focal signs, papilledema, seizures Corticosteroids to reduce intracranial pressure, treat the lesion

30 Clinical Approach The etiology of Alzheimer dementia is an unknown but Alzheimer disease has a genetic component. The risk of developing the disease for an individual in a family with Alzheimer disease increases by a factor of 3 or 4. The gene that codes for apoprotein E seems to be associated with some prediction. The pathologic changes in the brains of Alzheimer disease patients include neurofibrillary tangles with a deposition of abnormal amyloid in the brain. The etiology of Alzheimer dementia is an unknown but Alzheimer disease has a genetic component. The risk of developing the disease for an individual in a family with Alzheimer disease increases by a factor of 3 or 4. The gene that codes for apoprotein E seems to be associated with some prediction. The pathologic changes in the brains of Alzheimer disease patients include neurofibrillary tangles with a deposition of abnormal amyloid in the brain.

31 Amyloid Precursor Protein A-ß Neurofibrillary Tangles A-ß Aggregation Neuron Death Basal Forebrain and Brainstem Nuclei Neurotransmitter Deficits Neuritic Plaques Neuron Death Cortex Demantia Syndrome

32 Mutations and vulnerability genes associated with Alzheimer ’ s disease

33

34 Classical neuritic plaque (Bielschowsky silver stain)

35 Neurofibrillary Tangles

36 Neurofibrillary tangles (H&E stain)

37 Cerebral amyloid angiopathy (H&E stain)

38 Clinical Approach The disease onset can be very insidious and the average life expectancy after diagnosis is 7-10 years. The clinical course is characterized by the progressive decline of cognitive functions (memory, orientation, attention and concentration) and the development of psychological and behavioral symptoms (wandering, aggression, anxiety, depression and psychosis) (see Table 49-3) The disease onset can be very insidious and the average life expectancy after diagnosis is 7-10 years. The clinical course is characterized by the progressive decline of cognitive functions (memory, orientation, attention and concentration) and the development of psychological and behavioral symptoms (wandering, aggression, anxiety, depression and psychosis) (see Table 49-3)

39 Table 49-3 ALZHEIMER DISEASE CLINICAL COURSE CLINICAL STAGE MANIFESTATIONS Early Mild forgetfulness, poor concentration, fairly good function, denial, occasional disorientation Intermediate Drastic deficits for recent memory, can travel to familiar locations, suspicious, anxious, aware of confusion Late Cannot remember names of family members or close friends; may have delusions or hallucinations, agitation, aggression, wandering, disoriented to time and place, need for substantial care Advanced Totally incapacitated and disoriented, incontinent, personality and emotional changes; eventually all verbal and motor skills deteriorate, leading to need for total care

40 Treatment The goals of treatment in Alzheimer disease are to The goals of treatment in Alzheimer disease are to (a) improve cognitive function (a) improve cognitive function (b) reduce behavioral and psychological symptoms, and (b) reduce behavioral and psychological symptoms, and (c) improve the quality of life. (c) improve the quality of life.

41 Treatment Donepezil (Aricept) and revastigmine (Exelon) are cholinesterase inhibitors that are effective in improving cognitive function and global clinical state. Donepezil (Aricept) and revastigmine (Exelon) are cholinesterase inhibitors that are effective in improving cognitive function and global clinical state. Memantine ( Namenda) is the only NMDA receptor antagonist for moderate to severe Alzheimer dementia Memantine ( Namenda) is the only NMDA receptor antagonist for moderate to severe Alzheimer dementia Risperidone reduces psychotic symptoms and aggression in patients with dementia. Risperidone reduces psychotic symptoms and aggression in patients with dementia.

42 Treatment Other issues include wakefulness, nightwalking and wandering, aggression, incontinence, and depression. A structured environment, with predictability, and judicious use of pharmacotherapy, such as selective serotonin reuptake inhibitor (SSRI) for depression or short-acting benzodiazepine for insomnia, are helpful. Other issues include wakefulness, nightwalking and wandering, aggression, incontinence, and depression. A structured environment, with predictability, and judicious use of pharmacotherapy, such as selective serotonin reuptake inhibitor (SSRI) for depression or short-acting benzodiazepine for insomnia, are helpful.

43 Opportunities for treatment of AD Enhancement of cholinergic function Enhancement of cholinergic function Cholinesterase inhibitors Cholinesterase inhibitors Tacrine Tacrine Donepezil (Aricept) Donepezil (Aricept) Rivastigmine ( Exelon) Rivastigmine ( Exelon) Huperzine A Huperzine A Cholinesterase receptor agonists Cholinesterase receptor agonists NMDA receptor antagonist NMDA receptor antagonist Memantine( Namenda) Memantine( Namenda)

44 Treatment The primary caregiver is a often overwhelmed and needs support. The Alzheimer Association is a national organization developed to give support to family members, and can be contacted through The primary caregiver is a often overwhelmed and needs support. The Alzheimer Association is a national organization developed to give support to family members, and can be contacted through

45 Comprehension Questions Comprehension Questions

46 [1] A 78-year-old female is diagnosed with Alzheimer disease. Which of the following agents is most likely to help with the cognitive function? A. Haloperidol A. Haloperidol B. Estrogen replacement therapy B. Estrogen replacement therapy C. Donepezil C. Donepezil D. High dose Vitamin B 12 injections D. High dose Vitamin B 12 injections

47 ANSWER [1] C. Cholinesterase inhibitors help with the cognitive function in Alzheimer disease and may slow the progression somewhat. [1] C. Cholinesterase inhibitors help with the cognitive function in Alzheimer disease and may slow the progression somewhat.

48 [2] A 74-year-old male was noted to have excellent cognitive and motor skill 12 months ago. His wife noted that 6 months ago, his function deteriorated in a noticeable way, and, again, 2 months ago, another level of deterioration was noted. Which of the following is most likely to reveal the etiology of his functional decline? [2] A 74-year-old male was noted to have excellent cognitive and motor skill 12 months ago. His wife noted that 6 months ago, his function deteriorated in a noticeable way, and, again, 2 months ago, another level of deterioration was noted. Which of the following is most likely to reveal the etiology of his functional decline? A. HIV Antibody test A. HIV Antibody test B. Magnetic resonance imaging of the brain B. Magnetic resonance imaging of the brain C. Cerebrospinal fluid VDRL test C. Cerebrospinal fluid VDRL test D. Serum thyroid-stimulating hormone (TSH) D. Serum thyroid-stimulating hormone (TSH)

49 ANSWER [2] B. The stepwise decline in function is typical for multi-infarct dementia, diagnosed by viewing multiple areas of the brain infarct. [2] B. The stepwise decline in function is typical for multi-infarct dementia, diagnosed by viewing multiple areas of the brain infarct.

50 [3] A 55-year-old man is noted by his family members to be forgetful and become disoriented. He also has difficulty making it to the bathroom in time, and complains of feeling as though “ he is walking like he was drunk ”. Which therapy is most likely to improve his condition? [3] A 55-year-old man is noted by his family members to be forgetful and become disoriented. He also has difficulty making it to the bathroom in time, and complains of feeling as though “ he is walking like he was drunk ”. Which therapy is most likely to improve his condition? A. Intravenous penicillin for 21 days A. Intravenous penicillin for 21 days B. Rivastigmine B. Rivastigmine C. Treatment with fluoxetine for 9 to 12 months\ C. Treatment with fluoxetine for 9 to 12 months\ D. Ventriculoperitoneal shunt D. Ventriculoperitoneal shunt E. Enrollment into Alcoholic Anonymous E. Enrollment into Alcoholic Anonymous

51 ANSWER [3] D. The classic triad for normal pressure hydrocephalus is dementia, incontinence, and gait disturbance; one treatment is shunting the cerebrospinal fluid. [3] D. The classic triad for normal pressure hydrocephalus is dementia, incontinence, and gait disturbance; one treatment is shunting the cerebrospinal fluid.

52 [4] Which of the following commonly seen in brain imaging of patients with Alzheimer disease? [4] Which of the following commonly seen in brain imaging of patients with Alzheimer disease? A. Normal cerebral ventricles and atrophic brain tissue A. Normal cerebral ventricles and atrophic brain tissue B. Enlarged cerebral ventricles and atrophic brain tissue B. Enlarged cerebral ventricles and atrophic brain tissue C. Enlarged cerebral ventricles and no atrophy of brain tissue C. Enlarged cerebral ventricles and no atrophy of brain tissue D. Normal cerebral ventricles and normal brain tissue, acetylcholine deficiency D. Normal cerebral ventricles and normal brain tissue, acetylcholine deficiency

53 ANSWER [4] B. Alzheimer disease typically has enlarged cerebral ventricles and brain atrophy, whereas normal pressure hydrocephalus has enlarged brain ventricles without brain atrophy. [4] B. Alzheimer disease typically has enlarged cerebral ventricles and brain atrophy, whereas normal pressure hydrocephalus has enlarged brain ventricles without brain atrophy.

54 CLINICAL PEARLS Alzheimer disease is the most common type of dementia, followed by multi-infarct (arteriosclerotic) dememtia. Alzheimer disease is the most common type of dementia, followed by multi-infarct (arteriosclerotic) dememtia. Approximately 5% of people older than age of 65 years and 20% older than age 80 years have some form of dementia. Approximately 5% of people older than age of 65 years and 20% older than age 80 years have some form of dementia.

55 CLINICAL PEARLS Depression and reversible causes of dementia should be considered in the evaluation of a patient with memory loss and functional decline. Depression and reversible causes of dementia should be considered in the evaluation of a patient with memory loss and functional decline. A cholinesterase inhibitor such as donepezil is effective in improving cognitive function and global clinical state in patients with Alzheimer disease. A cholinesterase inhibitor such as donepezil is effective in improving cognitive function and global clinical state in patients with Alzheimer disease.

56 THANKS! THANKS!

57


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