WHAT IS DEMENTIA? An acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient

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1 DEMENTIA

2 WHAT IS DEMENTIA? An acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient Progressive and disabling Not an inherent aspect of aging Different from normal cognitive lapses Slide 2

3 THE EPIDEMIOLOGY OF ALZHEIMER S DISEASE 6% 8% of people age 65+ have AD Nearly 30% of those aged 85+ have AD Slide 3

4 Millions of people THE EPIDEMIOLOGY OF ALZHEIMER S DISEASE (AD) (1 of 2) Present Est by million in U.S. currently 14 million in U.S. by 2050 Life expectancy of 8 10 years after symptoms begin Slide 4

5 Economic THE IMPACT OF DEMENTIA $100 billion annually for care and lost productivity Medicare, Medicaid, private insurance provide only partial coverage Families bear greatest burden of expense Emotional Direct toll on patients Nearly half of caregivers suffer depression Slide 5

6 RISK FACTORS FOR DEMENTIA Definite Age Down syndrome Family history APOE4 allele Possible Head injury Fewer years of education Late onset of major depression Cardiovascular risk factors Slide 6

7 POSSIBLE PROTECTIVE FACTORS NSAIDs Antioxidants Statins Physical activity Intellectual activity Slide 8

8 THE GENETICS OF DEMENTIA Mutations of chromosomes 1, 14, 21 Rare early-onset (before age 60) familial forms of dementia Down syndrome Apolipoprotein E4 on chromosome 19 Late-onset AD APOE*4 allele risk & onset age in doserelated fashion APOE*2 allele may have protective effect Slide 8

9 Cognitive Evaluation Memory: rep statements, misplacing items, stm, ltm, immediate recall Language: speech fluency, comprehension, reading, writing, word finding, content of speech Visual spatial function: getting lost, driving Executive Functioning: planning, flexibility, organization, multistep tasks Personality/ Behavior: apathy, agitation, depression, hallucinations, delusions Motor: gait, falls, temor, weakness, coordination Attention Slide 9

10 ASSESSMENT: HISTORY Ask both the patient & a reliable informant about the patient s: Current condition Medical history Current medications & medication history Patterns of alcohol use or abuse Living arrangements Slide 10

11 ASSESSMENT: PHYSICAL Examine: Neurologic status Mental status Functional status Include: Quantified screens for cognition eg, Folstein s MMSE, Mini-Cog Neuropsychologic testing Slide 11

12 ASSESSMENT: LABORATORY Blood chemistries CBC Liver function tests Urinalysis Serologic tests for: RPR TSH Vitamin B 12 level Folate level

13 ASSESSMENT: BRAIN IMAGING Consider imaging when: Onset occurs at age <65 years Symptoms have occurred for <2 years Neurologic signs are asymmetric or focal Clinical picture suggests normal-pressure hydrocephalus Patient has had recent fall or other head trauma Consider: Noncontrast computed topography head scan Magnetic resonance imaging Positron emission tomography Slide 13

14 Normal aging DIFFERENTIAL DIAGNOSIS Mild cognitive impairment Delirium Depression Alzheimer s disease Vascular (multi-infarct) dementia Dementia associated with Lewy bodies Other (alcohol, Parkinson's disease, Pick s disease, frontal lobe dementia, neurosyphilis) Slide 14

15 NORMAL AGING No consistent, progressive deviations on testing of memory Some decline in processing and recall of new information: slower, harder Reminders work visual tips, notes Absence of significant effects on ADLs or IADLs due to cognition Slide 15

16 MILD COGNITIVE IMPAIRMENT Memory problem without deficits in other domains No functional impairment 12% per year progress to Alzheimer s disease Slide 16

17 DELIRIUM vs DEMENTIA Delirium and dementia often occur together in older hospitalized patients; the distinguishing signs of delirium are: Acute onset Cognitive fluctuations over hours or days Impaired consciousness and attention Altered sleep cycles Slide 17

18 DEPRESSION vs DEMENTIA (1 of 2) The symptoms of depression and dementia often overlap: Impaired concentration Lack of motivation, loss of interest, apathy Psychomotor retardation Sleep disturbance Slide 18

19 DEPRESSION vs DEMENTIA (2 of 2) Patients with primary depression are generally unlike those with dementia in that they: Demonstrate motivation during cognitive testing Express cognitive complaints that exceed measured deficits Maintain language and motor skills Effective treatment of depressive symptoms may improve cognition Slide 19

20 Onset: gradual ALZHEIMER S DISEASE Cognitive symptoms: primarily memory with difficulty learning new information Motor symptoms: rare early, apraxia later Progression: gradual, over 8 10 yr on average Lab tests: normal Imaging: possible global atrophy, small hippocampal volumes Slide 20

21 AD Cognitive Symptoms Begins with memory and spreads to include language and visual-spatial areas Lack of insight into deficits ( anasognosia) Apraxia: difficulty performing motor tasks develops later Executive function: most evident in middle and late stages Neuropsychiatric: common in middle and late, but apathy may be seen early Slide 21 20% of AD patients may present atypically with nonmemory complaints such as word finding, organizational or navigational problems

22 Alzheimers Disease PATH FINDINGS: - Neuritic plaque: amyloid - Neurofibrillary tangles: tau protein correlates more with cognitive decline than does amyloid plaque AUTOPSY: most severe pathology is found in the hippocampus, temporal cortex, and nucleus basalis of Meynert BIOCHEMICALLY: decrease in acetylcholine, choline acetyltransferase and nicotinic cholinergic receptors Slide 22

23 DSM-IV DIAGNOSTIC CRITERIA FOR AD Development of cognitive deficits manifested by: Impaired memory and Aphasia, apraxia, agnosia, disturbed executive function Significantly impaired social, occupational function Gradual onset, continuing decline Not due to CNS or other physical conditions (eg, PD, delirium) Not due to an Axis I disorder (eg, schizophrenia) Slide 23

24 LEWY BODY DEMENTIA Onset: gradual Cognitive symptoms: memory, visuospatial, hallucinations, fluctuations Motor symptoms: parkinsonism Progression: gradual, but usually faster than AD Lab tests: normal Imaging: possible global atrophy Slide 24

25 VASCULAR DEMENTIA Onset: may be sudden/stepwise Cognitive symptoms: depend on anatomy of ischemia Motor symptoms: correlates with ischemia Progression: stepwise with further ischemia Lab tests: normal Imaging: cortical or subcortical changes on MRI Slide 25

26 DSM-IV DIAGNOSTIC CRITERIA FOR VASCULAR DEMENTIA Development of cognitive deficits manifested by: Impaired memory and Aphasia, apraxia, agnosia, disturbed executive function Significantly impaired social, occupational function Focal neurologic symptoms & signs or evidence of cerebrovascular disease Deficits occur in absence of delirium Slide 26

27 FRONTOTEMPORAL DEMENTIA Onset: gradual, usually age <60 Cognitive symptoms: executive: disinhibition, apathy, behavior changes Motor symptoms: none; may be associated with ALS in rare cases Progression: gradual but faster than AD Lab tests: normal Imaging: atrophy in frontal and temporal lobes Slide 27

28 Less Common Causes of Dementia Vitamin deficiencies: B1 (WK), B12 Endocrine: thyroid AI, Cushings, Hypperparathryoidism Organ failure: renal, liver Chronic infections: HIV, Papovavirus ( ML), CJD, Tuberculosis, Fungal, Protozoal, NS Head trauma/diffuse brain damage: subdural, postencephalitis, NPH Neoplastic: primary, metastatic, paraneoplastic Slide 28 limbic encephalitis, meningeal carcinomatosis

29 Less Common Causes of Dementia Toxic: alcohol, drug, heavy metal Psychiatric Deg disorders: Huntington s disease, ALS, Downs Miscellaneous: sarcoidosis, vasculitis, recurrent nonconvulsive seizures Metabolic disorders: Wilson s disease, mitochondrial dysfunction Slide 29

30 NONPHARMACOLOGIC MANAGEMENT Cognitive rehabilitation Individual and group therapy Physical and mental activity Regular appointments Family and caregiver education and support Environmental modification Attention to safety Slide 30

31 PHARMACOLOGIC MANAGEMENT Treatment should be individualized Cholinesterase inhibitors: donepezil, rivastigmine, galantamine Memantine Other cognitive enhancers Antidepressants Psychoactive medications Slide 31

32 CHOLINESTERASE INHIBITORS Slow breakdown of acetylcholine Clinical trials demonstrate modest delay in cognitive decline compared with placebo GI side effects common No evidence of difference in efficacy among drugs Slide 32

33 MEMANTINE Neuroprotective effect is to reduce glutamatemediated excitotoxicity Modest benefit on cognition, ADLs, and behavior FDA-approved for moderate to severe AD Common adverse events: Constipation Dizziness Headache Slide 33

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