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  2. 2. What is Dementia?What is Dementia? ♠ Dementia is a term used to describe a cluster of symptoms including: ‫ﻂ‬ Forgetfulness (progressive) ‫ﻂ‬ Difficulty doing familiar tasks ‫ﻂ‬ Confusion ‫ﻂ‬ Poor judgment ‫ﻂ‬ Decline in intellectual functioning ‫ﻂ‬ Dementia is not the name of an actual disease ‫ﻂ‬ Dementia is not a part of normal aging
  3. 3. Table 8. Diagnostic Criteria for Dementia (DSM-IV) ♠ Memory impairment: impaired ability to learn new information or to recall old information ♠ One or more of the following: aphasia (language disturbance); apraxia (impaired ability to carry out motor activities despite intact motor function); agnosia (failure to recognize or identify objects despite intact sensory function); disturbance in executive functioning-impaired ability to plan, organize, sequence, abstract ♠ The cognitive deficits result in functional impairment (social/occupational) ♠ The cognitive deficits do not occur exclusively solely during a delirium ♠ NOT due to other medical or psychiatric conditions
  4. 4. Causes of DementiaCauses of Dementia Alzheimer’s disease (approximately 70%) Vascular dementia – (Strokes and TIA’s) Parkinson’s disease Frontotemporal dementia (FTD) Normal-Pressure hydrocephalus (NPH) Dementia with Lewy Bodies Delirium/Depression Other, less common causes
  5. 5. Clinical course
  6. 6. ALZHEIMERALZHEIMER DISEASEDISEASEprogressive neurologic disorder that results in memory loss, personality changes, global cognitive dysfunction, and functional impairments. Loss of short-term memory is most prominent early. In the late stages of disease, patients are totally dependent upon others for ADLS the most common form of dementia in the elderly, accounting for 60 to 80 % of cases estimated to affect more than 4 million Americans
  7. 7. DiagnosisDiagnosis ♣ Clinical diagnosis ♣ History, mental status evaluation, physical examination, limited laboratory testing, and in many cases, neuroimaging, more extensive neuropsychological testing and a depression screen. ♣ An MRI finding of bilateral hippocampal atrophy suggests AD, but is not specific or sensitive ♣ The laboratory testing includes a CBC, electrolytes, glucose, BUN and creatinine, serum B12, TSH and liver function tests.
  8. 8. Pathology of ADPathology of AD ۩ There are 3 consistent neuropathologicalhallmarks: – Amyloid-rich senile plaques – Neurofibrillarytangles – Neuronal degeneration ۩ These changes eventually lead to clinical symptoms, but they begin years before the onset of symptoms
  9. 9. AcetylcholinesteraseAcetylcholinesterase InhibitorsInhibitors ‫ۺ‬Drugs used to treat Alzheimer’s disease act by inhibiting acetylcholinesterase activity ‫ۺ‬These drugs block the esterase- mediated metabolism of acetylcholine to choline and acetate. This results in: – Increased acetylcholine in the synaptic cleft – Increased availability of acetylcholine for postsynaptic and presynaptic nicotinic (and muscarinic) acetylcholine receptors
  10. 10. VASCULAR DEMENTIA VASCULAR DEMENTIA  The onset of cognitive deficits associated with a stroke Abrupt onset of symptoms followed by stepwise deterioration Findings on neurologic examination consistent with prior stroke(s) Infarcts on cerebral imaging
  11. 11. criteria for probable vascular dementia ♫Cerebrovascular disease evident on history, examination or imaging ♫Two disorders must be related by – onset of dementia within 3 months or – abrupt, fluctuating or stepwise progression
  12. 12. Features that make vascular dementia uncertain or unlikely ♦ Early memory loss and progressive deterioration in the absence of corresponding focal lesions on imaging ♦ Absence of focal neurological signs ♦ Absence of cerebrovascular lesions on CT or MRI
  13. 13. Clinical features supportive of vascular dementia Early gait disorder Frequent falls Urinary incontinence or frequency early in disorder Pseudobulbar palsy Personality and mood changes
  14. 14. FRONTOTEMPORALFRONTOTEMPORAL DEMENTIADEMENTIA characterized by focal atrophy of the frontal and temporal lobes in the absence of Alzheimer pathology Pick's disease was the first recognized subtype of FTD, one that is characterized pathologically by the presence of Pick bodies (silver staining intracytoplasmic inclusions) in the neocortex and hippocampus. Clinically, presents with language abnormalities and behavioral disturbances.
  15. 15. FRONTOTEMPORALFRONTOTEMPORAL DEMENTIADEMENTIA occurs between the ages of 35 and 75 years, and only rarely after age 75; the mean age of onset is the sixth decade Both sexes are equally affected. Familial occurrence occurs in 20 to 40 percent of cases and may be associated with a variety of identified mutations in the tau gene on chromosome 17
  16. 16. Frontotemporal Lobe Dementia Core Features • Insidious onset and gradual progression • Early decline in social/interpersonal conduct • Early impairment in personal conduct • Early loss of insight • Early emotional blunting Supportive Features • Behavior disorder – hygiene, grooming, mental rigidity, dietary changes, perseverative behavior • Speech and language – perseveration, mutism, economy of speech • Physical signs – akinesis, rigidity, tremor, labile BP
  17. 17. Normal-PressureNormal-Pressure HydrocephalusHydrocephalus a condition of pathologically enlarged ventricular size with normal opening pressures on lumbar puncture triad of dementia, gait disturbance, and urinary incontinence reversible by the placement of a ventriculoperitoneal shunt
  18. 18. Core And Supportive Features For Clinical Diagnosis Of DLB 1. The central feature required for a diagnosis of DLB is progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function 2. Two of the following core features are essential for a diagnosis of probable DLB, and one is essential for possible DLB. • Fluctuating cognition with pronounced variations in atten- tion and alertness • Recurrent visual hallucinations that are typically well formed and detailed. • Spontaneous motor features of parkinsonism. 3. Features supportive of the diagnosis are • repeated falls • syncope • transient loss of consciousness • neuroleptic sensitivity • systematized delusions • hallucinations in other modalities.
  19. 19. Dementia with LewyDementia with Lewy BodiesBodies the most common dementia syndrome associated with parkinsonism  the second most common form of neurodegenerative dementia after Alzheimer disease (AD).  characterized by dementia accompanied by delirium, visual hallucinations, and parkinsonism. Other common symptoms include syncope, falls, sleep disorders, and depression.  The presence of both Lewy bodies and amyloid plaques with deficiencies in both acetylcholine and dopamine neurotransmitters suggests that dementia with Lewy bodies represents the middle of a disease spectrum ranging from Alzheimer’s disease to Parkinson’s disease
  20. 20. Parkinson’s diseaseParkinson’s disease ♠ Cardinal motor features • Brady- and akinesia • Rigidity • Resting tremor • Postural instability ♠ Dementia typically occurs in the last half of the clinical course of PD, whereas it is often one of the presenting features of DLB.
  21. 21. Progressive supranuclear palsy Progressive supranuclear palsy  also known as Steele Richardson Olszewski syndrome a rare syndrome that can mimic PD in its early phase Characteristic features of PSP – vertical supranuclear palsy with downward gaze abnormalities – postural instability with unexplained falls – Bradykinesia and rigidity are typically symmetrical in onset – Apathy, disinhibition, dysphoria, and anxiety are common
  22. 22. classic neuropathologic features of PSP ♣ globose neurofibrillary tangles (NFT) consisting of hyperphosphorylated tau proteins. ♣ These lesions and accompanying neuronal loss are seen primarily in the substantia nigra, subthalamic nucleus, globus pallidus, superior colliculus and midbrain, and pontine reticular formation. ♣ Cortical involvement is more variable but predominately affects the frontal lobes.
  23. 23. 1. What criterion is required for the diagnosis of Alzheimer’s disease? A) Disturbances in consciousness B) Static loss of memory function C) Impairment of two areas of cognition D) Changes in personality E) Myoclonus
  24. 24. 1. (C) Impairment of two areas of cognition. The diagnosis of Alzheimer’s disease requires impairment of two areas of cognition, no disturbance in consciousness, progressive loss of memory function, and no systemic disease or disorder to account for dementia. Although changes in personality and myoclonus mayoccur in patients with Alzheimer’s disease, these changes are not required for the diagnosis.
  25. 25. A 72-year-old woman is admitted to the hospital with agitation and visual hallucinations. The patient’s symptoms started 1 year ago, and 6 months later, the patient started to have fluctuating cognitive impairments. Physical examination reveals tremor and rigidity.
  26. 26. 2. Which of the following is this patient’s most likely diagnosis? (A) Alzheimer’s disease (B) Corticobasal degeneration (C) Dementia with Lewy bodies (D) Multi-infarct dementia (E) Progressive supranuclear palsy
  27. 27. 3. Which of the following medications is the most appropriate for the long-term management of the patient’s visual hallucinations and agitation? (A) Amitriptyline (B) Chlorpromazine (C) Haloperidol (D) Quetiapine (E) Thioridazine
  28. 28. 2. (C) Dementia with Lewy bodies. This patient has dementia with Lewy bodies, which is a Parkinson plus syndrome. The central feature of dementia with Lewy bodies is progressive cognitive decline in addition to 3 defining features: pronounced “fluctuations” in alertness and attention, recurrent visual hallucinations, and parkinsonian motor symptoms. 3. (D) Quetiapine. Typical antipsychotics, such as haloperidol, and newer agents with dopamine D2 receptor affinity are avoided in the long-term treatment of visual hallucinations and agitation because of potential worsening of motor symptoms, cognitive decline, delirium, and features of neuroleptic malignant syndrome associated with dopamine receptor blockage. Amitriptyline is not indicated for psychosis.
  29. 29. 4. A 72-year-old man presents to the emergency department after a fall. He states that he has fallen frequently over the past 8 months. On examination, he has no tremor, but he has generalized rigidity (mostly axial), bradykinesia, increased gag reflex, and difficulty with vertical gaze. What is this patient’s most likely diagnosis? (A) Corticobasal degeneration (B) Multiple system atrophy (C) Parkinson’s disease (D) Parkinsonism-dementia-amyotrophic lateral sclerosis (E) Progressive supranuclear palsy
  30. 30. 4. (E) Progressive supranuclear palsy. Progressive supranuclear palsy is a neurodegenerative disease that presents with primarily vertical gaze dysfunction accompanied by extrapyramidal symptoms and cognitive dysfunction. The disease usually develops after the fourth decade of life, and the diagnosis is purely clinical.
  31. 31. 5. Which of the following studies should be included in the laboratory work-up for Alzheimer’s disease? A) Imaging studies of the brain B) Assessment of thyroid hormone levels C) Liver function tests D) Imaging studies of the brain and assessment of thyroid hormone levels E) Imaging studies of the brain, assessment of thyroid hormone levels, and liver function tests
  32. 32. 5. (E) Imaging studies of the brain, assessment of thyroid hormone levels, and liver function tests. A laboratory work-up for Alzheimer’s disease should include imaging studies of the brain, assessment of thyroid hormone levels, and liver function tests, as well as assessment of vitamin B12 levels, urinalysis, VDRL/fluorescent treponemal antibody absorbed, cerebrospinal fluid analysis, and electroencephalography.