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31 Cards in this Set
- Front
- Back
At the most general level, what characterizes dementia?
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Dementia is characterized by:
- progressive deterioration in intellectual function and other cognitive skills, leading to a decline in ability to perform activities of daily living in the absence of delirium |
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Explain the epidemiology of dementia?
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-affects only 1% of people 60-64 but 30-50% of those above 85
- prevalence of dementia doubles every five years after age 60, until age 90 -more than five million affected with AD in US - dementia is leading cause of institutionalization among the elderly |
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How can we keep synapses in our brains healthy?
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- determine and promote the factors that promote longevity and healthy brain aging
- staying mentally and physically active - staying socially engaged - controlling CV risk factors; weight, BP, chol, blood sugar, stop smoking -eating a balanced diet |
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T/F There is normal cognitive decline with aging
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TRUE
There is some normal decline in cognitive function as we age. In particular we note normal declines in 1) verbal abilities, e.g. proper word finding 2) memorizing/new learning; still able to memorize and learn new words, but it may take longer and be less efficient 3) abstraction 4) reaction time (slows down) 5) central processing These cognitive functions do not substantially progress or significantly impair daily functioning. Older people may learn new information and recall previously learned information but may do so less rapidly and efficiently. |
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What are the DSM IV criteria for dementia?
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Development of multiple cognitive deficits manifested by:
1) memory impairment 2) one or more of the following cognitive disturbances: a) aphasia b) apraxia c) agnosia d) disturbance in executive functioning (which impairs daily function) cognitive deficits each cause SIGNIFICANT IMPAIRMENT in social or occupational functioning and represent a SIGNIFICANT DECLINE from a previous level of functioning MOREOVER... deficits DO NOT OCCUR exclusively during the COURSE OF DELIRIUM deficits are NOT better accounted for by another AXIS 1 disorder |
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What are the differential diagnoses of dementia?
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Alzheimer’s disease (most common, generally with cerebrovascular disease together)
Parkinson’s disease with dementia Prion disease Cerebrovascular disease (VaD) Frontotemporal dementia (FTD) Dementia with Lewy Bodies (DLB) Normal pressure hydrocephalus (NPH) |
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What are the pathological hallmarks of dementia?
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AD: amyloid plaques and tau neurofibrillary tangles
DLB: Lewy bodies made of alpha synuclein protein VaD: large or small vessel infarcts and incomplete infarction FTD: tau tangles, Pick bodies, intranuclear inclusions |
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What are the risk factors for Alzheimer's disease?
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- the biggest risk factor for Alzheimer's disease is AGE
- DEMENTIA is actually a late stage of Alzheimers: the disease starts many years before the onset of symptoms |
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1) What is the disease course of Alzheimer's? 2) What do we see during the silent period of the disease? 3) What is the order of symptoms?
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1-2) Disease starts long before symptoms appear.
Silent period of the disease during which: 1) soluble amyloid protein forms 2) insoluble amyloid forms next and begin to accumulate 3) immunological reactivity begins, but there are no symptoms 4) symptoms begin AD can be silent for 10-20 years before cognitive decline 3) Order of symptoms is: 1) Presymptomatic: preclinical AD; there are physiological changes, but no cognitive impairment 2) Mild Cognitive Impairment (MCI): due to AD, patients begin to decline cognitively 3) AD Dementia (mild moderate severe): patient begins to have impaired daily functioning We have begun to reconceptualize the diagnosis of AD 1) BEFORE someone had to have dementia before you could diagnose it 2) NOW: newer evidence can substantiate that AD begins many years before clinical symptoms |
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What is the pathology of Alzheimer's disease?
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- patients have abundant neuritic plaques and neurofibrillary tangles
- loss of cholinergic neurons in nucleus basalis of Meynert, which are the origin of cholinergic supply for the cortex -the plaques consist of neurites (axons or dendrites), astrocytes, and microglial cells around an amyloid core; these are extracellular - tangles consist of paired helical filaments that contain hyperphosphorylated tau protein, these are intracellular - there is also cerebral atrophy (particularly in medial temporal), enlarged ventricles |
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What tracer can be used with a PET to identify the amyloid plagues associated with AD?
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Florbetapir
- these tracers bind to amyloid plaques and aid in diagnosis of AD |
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Based on the information derived from amyloid PET scans and other markers what is the theoretical model that shows how AD might progress?
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- amyloid accumulates before symptoms begin
- increases over time in tau in spinal fluid; tau leaks out of degenerating neurons - also decreases in the MRI volume of the brain - if one has a moderate amount of amyloid + at least 1 lacunar infarct, they are much more likely to have dementia than if they had one or the other, but not both |
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What are the stages of Alzheimer's disease?
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1) mild cognitive impairment
- Mild subjective and/or objective memory loss - Normal ADL function - MMSE = 25-30 2) mild-moderate dementia - Forgetfulness - Short-term memory loss - Repetitive questions - Hobbies, interests lost - Impaired instrumental functions - Anomia - MMSE = 20-26 3) moderate dementia - Progression of cognitive deficits - Aphasia - Dysexecutive syndrome - Impaired BADL - Transitions in care - MMSE = 10-20 4) severe Alzheimer's disease - Agitation - Altered sleep patterns - Total dependence: dressing, feeding, bathing - MMSE <10 - Hippocampus is affected early - association areas near by in temporal, parietal are spared until later in the disease -better correlation btw tangles and dementia than between plaque and dementia |
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Alzheimer's disease produces certain vascular changes. What do the following lesions look like and explain what occurs in each lesion? 1) FLARE 2) Microhemorrhages 3) inflammatory form of amyloid angiography
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LEFT: Flare
-white is abnormal; see lacunar infarcts as a sign of microvascular disease MIDDLE: micro hemorrhages -black dots in the central image; this is a sign of amyloid deposition in amyloid angiography in blood vessels -amyloid angiography refers to deposition of beta amyloid in the media and adventitia of small and mid-sized arteries (and less frequently, veins) of the cerebral cortex and leptomeninges RIGHT: INFLAMMATORY FORM OF AMYLOID ANGIOGRAPHY with micro and macro changes |
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What are the CSF biomarkers of Alzheimer's disease?
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Beta-amyloid and Phosphotau & Tau
Beta-amyloid 1) see changes in the amount of beta-amyloid in CSF 2) beta-amylod gets bound in plaques during AD 3) there is less beta-amyloid in CSF before onset of dementia Phosphatau & tau 1) these go up in CSF in AD 2) this happens because these leak out of dying cells |
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What are the genetic markers for Alzheimer's disease?
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ApoE4 allele
- does not tell if you have or will get AD...merely tell you you have risk alleles for the disease Presenilin 1, 2, or 3 - 100% penetrant mutation that causes AD in a small subset of the population, used to study the disease timecourse - MRI and PET can show signs 5 years before onset, and amyloid accumulation can begin 15-20 years before onset |
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Explain the relevance and use of the term Mild Cognitive Impairment.
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- MCI recent term used to describe cognitive loss (often memory) not severe enough to meet dementia criteria but beyond normal
- up to 50% of patients with mild cognitive impairment that affects memory develop dementia within 3 years - MCI patients are under intense study to try to develop preventive or delaying interventions |
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1) What drugs are primarily used to treat Alzheimer's Disease?
2) What is their mechanism of action? 3) What are the benefits of the treatment 4) What are the long term effects on cognition? 5) What are the side effects |
1) Cholinesterase inhibitors: tacrine donepezil rivastigmine galantamine
2) inhibit cholinesterase 3) Benefits a. stabilize functioning during the first year and make subsequent decline more gradual b. delay time to nursing home placement c. may decrease behavioral symptoms d. show some benefit in moderate to severe stages of AD e. cholinesterase inhibitors have similar efficacy but may have differences in tolerability and ease of use 4) long term effects of donezepil on cognition a. decline more gradual than would have been but still occurs b. only a modest benefit 5. side effects a. GI: nausea, vomiting, loose stools, diarrhea b. anorexia and weight loss c. vivid dreaming d. symptoms are usually transient and does related; titrate slowly and take with food e. small % agitated on cholinesterase inhibitors f. rivastigmine available as a patch which may decrease GI S/E |
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What other drug is used to treat Alzheimer's disease? What is its mechanism of action?
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Memantine (trade name Nameda)
NMDA inhibitor Used in addition to cholinesterase inhibitors for moderate to severe AD |
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What are the neuropsychiatric symptoms in AD?
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-apathy: occurs early, makes patients less motivated and more withdrawn; usually more upsetting to family than patient, not usually helped by SSRIs
- delusions - hallucinations - agitation - dysphoria - disinhibition symptoms make care more difficult |
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What are ways to help caregivers cope with AD?
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Facing the situation directly
Common sense problem solving Getting educated and developing a support network Familiar, calm environment with a predictable routine Keeping it simple, limit choices and matching activities to capacities and preferences Avoid arguing and overwhelming situations Driving and home safety Number one is figuring out what’s wrong and helping people to understand it |
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What are some examples of potential new treatments?
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- Agents that lower amyloid beta 2
- Potentially inhibit deposition of amyloid beta 2 through beta secretase inhibitors - Immunotherapy to remove plaques from brain and interfere with fibrillar forms of amyloid - Tau Hyperphosphorylation, Oxidation, Excitotoxicity, Inflammation, Apoptosis etc. |
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What are cases where AD prevention/delay is possible?
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Treating pre-symptomatic individuals at high risk
- Individuals with an autosomal dominant mutation - Individuals homozygous for ApoE4 - Individuals 70 and over with amyloid biomarker and no significant cognitive impairment |
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What is vascular dementia?
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- multi-infarct, strategic infarct, small vessel type (Binswangers)
- progression may be step wise - AD pathology may be present as well - executive dysfunction, apathy and depression are common - Rx - control of vascular risk factors, stroke prevention, off label use of cholinesterase inhibitors, SSRIs to treat behavioral symptoms 3 types - large vessel infarction - bilateral strategic thalamic infarcts - binswangers disease (small vessel) |
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What is dementia with lewy bodies?
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- diagnosis of probable DLB-dementia plus 2 of the following
1) parkinsonism 2) visual hallucinations 3) fluctuating alertness Supportive features: syncope, REM behavior disorder, depression, delusions, apathy, neuroleptic sensitivity Pathology: Lewy bodies (alpha synuclein) in the cortex, amyloid plaques, loss of cholinergic and dopaminergic neurons Rx: support and education for the patient and family, cholinesterase inhibitors, SSRIs, low dose neuroleptics (with care), dopaminergic medications |
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What is frontotemporal dementia?
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- often earlier onset than AD and more rapid decline
- behavioral variant - progressive aphasia - semantic dementia - FTD spectrum includes: Progressive supra nuclear palsy (PSP), corticobasal degeneration (CBD), and FTD amyotrophic lateral sclerosis (ALS) |
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What are some other causes of dementia?
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- toxic: alcohol or medications
- infectious: HIV, syphillis, lyme Creutzfeldt Jakob-prion disease (similar to mad cow); rapid decline -structural: head trauma or brain tumor 1) normal pressure hydrocephalus-gait impairment, urinary incontinence and cognitive decline 2) Dx: MRI, large volume spinal tap 3) Rx: programmable shunt SEE IMAGE ABOVE (explanation of image below) 1) ventricular enlargement disproportionate to the amount of atrophy 2) bowing of the corpus callosum 3) smooth rimming of high signal around the ventricles due to transependymal flow of CSF |
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What are the pathological hallmarks of Alzheimer's disease?
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amyloid plaques and tau neurofibrillary tangles
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What are the pathological hallmarks of dementia with lewy bodies?
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lewy bodies made of alpha synuclein protein
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What is the pathological hallmark of the dementia resulting from cerebrovascular disease?
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large or small vessel infarcts and incomplete infarction
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What are the pathological hallmarks of Frontotemporal dementia?
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tau tangles
Pick bodies intranuclear inclusions |