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1、CASE PRESENTATION Dr. LU, QINCHIDEPARTMENT OF NEUROLOGY REN JI HOSPITAL SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINETel: 58752345-3094 Email: qinchilu2021/9/101History A 68-year-old woman has been noted by her daughter to have memory loss and confusion. The daughter states that her mother has be

2、en 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has begun to become unable to take care of herself. 2021/9/102History The daughter states that her mother has become withdrawn and has lost interest in her usual activities, such as gard

3、ening and reading. Her mothers 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. 2021/9/103History The patients past medical history

4、 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. 2021/9/

5、104Physical 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 per

6、son, but she is not oriented to time and place. 2021/9/105Pyhsical & 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,

7、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.2021/9/106QuestionsWhat is the most likely diagnosis?What are the next diagnostic steps?What is

8、the best treatment for this condition?2021/9/107Summary: A 68-year-old woman has memory loss, confusion, and fatigue, and is withdrawn.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, i

9、s normal except for a low score on the MMSE.2021/9/108Most likely diagnosis: Alzheimer dementia. 2021/9/109Next diagnostic step: Assess for depression and reversible causes of dementia. 2021/9/1010Probable treatment: Acetylcholinesterase inhibitor 2021/9/1011 Analysis2021/9/1012ObjectivesKnow some o

10、f the common causes of dementiaUnderstand the presentation and diagnosis of Alzheimer dementiaKnow the treatment for Alzheimer dementia is acetylcholinesterase inhibitor2021/9/1013Considerations This is an elderly woman without any significant past medical history except for hypertension who was bro

11、ught 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. 2021/9/10

12、14Considerations The next step should be to rule out all the possible causes of reversible or arrestable dementia, such as multi-infarct dementia, hypothyroidism, drugs, B12 deficiency, normal pressure hydrocephalus, alcoholism, HIV, and syphilis. 2021/9/1015Considerations Laboratory tests will help

13、 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). 2021/9/1016Table 49-1ABBREVIATED WORKUP FOR DEMENTIAComplete bl

14、ood 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 radiographElectrocardiogram CT or MRI imaging of the head 2021/9/1017Considerations

15、 The possibility of HIV-induced dementia is not high on the differential in this case given the patients 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 sy

16、philis is indicated. 2021/9/1018Considerations 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 B12 deficiency and of hypothyroidism. The patient i

17、s 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. 2021/9/1019Considerations Therefore, in this case we are left with the possibility of multi-infarct dementia and Alz

18、heimer 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, Alzheim

19、er dementia becomes the most likely diagnosis.2021/9/1020 APPROACH TO DEMENTIA2021/9/1021DefinitionsAlzheimer 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 ge

20、neralized decline of intellectual ability from a previously attained level, usually without alteration of consciousness. 2021/9/1022DefinitionsMultiinfarct dementia: Numerous small cerebral vascular accidents, most commonly caused by atherosclerotic disease, leading to dementia.Normal pressure hydro

21、cephalus: 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.2021/9/1023Clinical Approach A patient who presents with memory and f

22、unctional impairment should be approached from the perspective that many etiologies can be causative. A thorough description of the patients cognitive, adaptive, memory, and behavioral ability over time is critical. Multiple family members are often needed to construct a complete and accurate pictur

23、e. The time frame (months to years versus days to weeks) is important. 2021/9/1024Clinical 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 r

24、emote), 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.2021/9/1025Clinical Approach The other intracranial diseases that could cause a dementia-like picture inclu

25、de 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 n

26、ot have. 2021/9/1026Clinical 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. 2021/9/1

27、027Table 49-2NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITYDISEASE 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 rivastigm

28、ine 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

29、and treat thrombus Parkinson disease Extrapyramidal signs (tremor, rigidity), slow onset Dopaminergic agents 2021/9/1028Table 49-2 (cont)NEUROLOGICAL DISEASES IMPAIRING COGNITIVE ABILITYDISEASE CLINICAL FEATURES TREATMENT HIV defintion Systemic involvement; risk factors for acquisition; positive HIV

30、 serology Treat specific infection Neurosyphilis Optic atrophy, Argyll-Robertson pupils, gait disturbance; positive cerebro-spinal fluid serology High dose intravenous penicillinMultiple sclerosis Brainstem signs, optic atrophy, long-standing disease with exacerbations and remissions; MRI showing wh

31、ite matter abnormalities Recombinant interferon, corticosteroids Intracranial tumor Focal signs, papilledema, seizures Corticosteroids to reduce intracranial pressure, treat the lesion 2021/9/1029Clinical Approach The etiology of Alzheimer dementia is an unknown but Alzheimer disease has a genetic c

32、omponent. 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 neurofibrill

33、ary tangles with a deposition of abnormal amyloid in the brain. 2021/9/1030Amyloid Precursor ProteinA-Neurofibrillary TanglesA- AggregationNeuron DeathBasal Forebrain and Brainstem NucleiNeurotransmitter DeficitsNeuritic PlaquesNeuron DeathCortexDemantia Syndrome2021/9/1031Mutations and vulnerabilit

34、y genes associated with Alzheimers disease2021/9/1032Mutations and vulnerability genes associated with Alzheimers disease2021/9/1033Classical neuritic plaque(Bielschowsky silver stain)2021/9/1034Neurofibrillary Tangles2021/9/1035Neurofibrillary tangles(H&E stain)2021/9/1036Cerebral amyloid angiopath

35、y(H&E stain)2021/9/1037Clinical 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 developmen

36、t of psychological and behavioral symptoms (wandering, aggression, anxiety, depression and psychosis) (see Table 49-3)2021/9/1038Table 49-3ALZHEIMER DISEASE CLINICAL COURSECLINICAL STAGE MANIFESTATIONS Early Mild forgetfulness, poor concentration, fairly good function, denial, occasional disorientat

37、ion 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 fo

38、r substantial care AdvancedTotally incapacitated and disoriented, incontinent, personality and emotional changes; eventually all verbal and motor skills deteriorate, leading to need for total care 2021/9/1039Treatment The goals of treatment in Alzheimer disease are to (a) improve cognitive function

39、(b) reduce behavioral and psychological symptoms, and (c) improve the quality of life. 2021/9/1040Treatment 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

40、receptor antagonist for moderate to severe Alzheimer dementiaRisperidone reduces psychotic symptoms and aggression in patients with dementia. 2021/9/1041Treatment Other issues include wakefulness, nightwalking and wandering, aggression, incontinence, and depression. A structured environment, with pr

41、edictability, and judicious use of pharmacotherapy, such as selective serotonin reuptake inhibitor (SSRI) for depression or short-acting benzodiazepine for insomnia, are helpful. 2021/9/1042Opportunities for treatment of ADEnhancement of cholinergic functionCholinesterase inhibitorsTacrineDonepezil

42、(Aricept)Rivastigmine ( Exelon)Huperzine ACholinesterase receptor agonistsNMDA receptor antagonistMemantine( Namenda)2021/9/1043Treatment2021/9/1044 Comprehension Questions2021/9/10451 A 78-year-old female is diagnosed with Alzheimer disease. Which of the following agents is most likely to help with

43、 the cognitive function?A. HaloperidolB. Estrogen replacement therapyC. DonepezilD. High dose Vitamin B12 injections2021/9/1046ANSWER 1 C. Cholinesterase inhibitors help with the cognitive function in Alzheimer disease and may slow the progression somewhat.2021/9/1047 2 A 74-year-old male was noted

44、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. HI

45、V Antibody testB. Magnetic resonance imaging of the brainC. Cerebrospinal fluid VDRL testD. Serum thyroid-stimulating hormone (TSH)2021/9/1048ANSWER 2 B. The stepwise decline in function is typical for multi-infarct dementia, diagnosed by viewing multiple areas of the brain infarct.2021/9/1049 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 li