Alzheimer Disease Flashcards
1
Q
Generally describe Alzhiemer disease
A
- an irreversible progressive brain disorder that slowly destroys memory & thinking abilities & eventually the ability to carry out simply ADLs
- Chronic neurodegenerative disease that starts slowly & worsens over time
- Leading cause of dementia
- Dementia is hallmark of Alzehiemer: defined as decrease in the ability to think & remember that is great enough to affect a person’s daily functioning
2
Q
What does not count as dementia
A
- Mild age related decline in short-term memory or benign senescent forgetfulness which does not lead to a regular functional problems or do not progress to other cognitive impairments
3
Q
Incidence of Alzhiemer disease (AD)
A
- 6th leading cause of death in the US but may rank 3rd
- Prevalence rises with age: 95% in >95 yrs
- Lifetime risk of developing AD is between 12-17%
- Higher prevalence in developed vs underdeveloped countries
4
Q
Etiology of Alzhiemer disease
A
- Cause is unknown
- Advanced age; abnormal processing of a normally occurring protein (Amyloid)
- Association with genetic predisposition: people with family Hx of AD at higher risk
- Apolipoprotein E (APOE) gene is a major genetic source of late onset AD: APOE 2 = neuroprotective and APOE 4 = increased risk
- Presence or absence of APOE 4 is not a definite criteria
- APOE 4 may play role in cholesterol transport, neural integrity, & amyloid processing/deposition
5
Q
Risk factors for Alzhiemer disease
A
- Age
- Genetics
- Dietary
- Environmental factors associated with immigration
- Vascular risk factors: systolic HTN, diabetes, hyperlipidemia; statins could be protective against AD
- Higher educated people have higher cognitive reserve to be able to adapt better to declining brain function
- Depression
6
Q
Possible protective factors against Alzhiemer disease
A
- Omega-3 fatty acids
- High educational level
- Regular exercise
- Moderate alcohol intake
- Vitamins C, E, B6, & B12
- Increased socialization
7
Q
What are the 2 most prominent neuropathological hallmarks of Alzhiemer disease
A
- Progressive accumulation of β-amyloid plaques and neurofibrillary tangles (NFTs)
8
Q
What does the accumulation of β-amyloid plaques and neurofibrillary tangles (NFTs) cause
A
- Sets off inflammatory processes causing breakdown in normal metabolic processes necessary for sustaining nerve cell functions
- Ultimately loss of neurons
9
Q
Describe β-amyloid
A
- A protein naturally occurring in brain tissue
- Created as a by-product of neuron function
- APOE appears to be involved in its metabolism leading to higher amounts of amyloid remaining in extracellular matrix
10
Q
Describe mutations in other genes seen with Alzhiemer disease
A
- Amyloid precursor protein (APP) gene, presenillin 1 & 2 genes (responsible for snipping APP) are associated with amyloid accumulation
- Snipping enzymes break APP abnormally leaving the fragments less soluble
11
Q
What is amyloid deposition thought of for Alzhiemer disease
A
- Researchers challenged it as a causative factor but think of it as fallout of neuron stress & a way for brain to adapt and protect neurons from death
12
Q
How does APP relate to both Alzhiemer disease and down syndrome
A
- In Down syndrome APP is overproduced. which leads to early onset AD
13
Q
What happens to β-amyloid proteins that remain in the extracellular matrix
A
- They fold on themselves abnormally & stick together creating plaques
- These plaques then attract other cellular debris like fragmented axons & altered glial cells which triggers inflammatory response & increases in free radicals leading to destruction of nearby neurons
14
Q
Describe the formation of Neurofibrillary Tangles (NFTs)
A
-Plaques in contact with neurons attract inflammatory responses & destroy microtubule structure by detaching Tau proteins (hold tubule together)
- Microtubules disintegrate and get engaged to form NFTs
- Destruction of microtubules cause disruptions in transport of NTs & molecules necessary to form NT receptors at synapses
- Synapes start to disintegrate & lose their function & structure: connections lost & neuron death
15
Q
What brain areas are affected with Alzhiemer disease
A
- Glutaminergic cortical neurons are most affected: pyramidal cells with corticocortical & hippocampus projections
- Progression of NFTs are observed starting from entorhinal cortex -> hippocampus -> limbic system -> all lobe cortices
- Some say it starts in the olfactory sulcus/bulb
- Areas affects are involved with learning/memory, behavior, mood, language
16
Q
What is the relationship between stroke and Alzhiemer disease
A
- Amyloid attacks smooth muscles of cerebral arteries making them weaker leading to strokes
17
Q
Clinical manifestations of Alzhiemer disease
A
- Early sx of mild forgetfulness may be overlooked as signs of natural aging
- Consistent mild memory loss for recent events may be indicative of Mild Cognitive Impairment (MCI)
- MCI is a significant sign of early stage AD
- Cognitive abilities become impaired
- Visuo-spatial memory deficits
- Sleep disorders: more awake time, EEG shows longer latencies to REM
- Loss of appetite
18
Q
What cognitive abilities become impaired in Alzhiemer disease
A
- Explicit memory more affected
- STM (short term memory) loss followed by LTM (long term memory) loss
- Language problems
- Difficulty with simple math problems
- impaired judgement
- Attention deficits
19
Q
What visa-spatial memory deficits are associated with Alzhiemer disease
A
- Navigating home
- Cooking
- Performing household chores become difficult
- Misplacing items
20
Q
Sensory problems with Alzhiemer disease
A
- Olfactory dysfunction (loss of smell, early sign of progressive from MCI to AD)
- Auditory problems
21
Q
Behavior and mood changes related to Alzhiemer disease
A
- Anxious
- Aggressive
- Restless
- Irritable outside of comfort zone
- Impulsive
- Egocentric
- Indifference (apathy)
- Withdrawn from social situations
- Depression
- Wandering
22
Q
40-60% of late stage AD show severe psychotic problems like
A
- Hallucinations
- Delusions
- Dramatic emotional & physical outbursts
23
Q
Abnormal motor signs in later stages of AD
A
- Tremors
- Bradykinesia
- Slow reaction times
- Balance problems
- Posture gait impairments
24
Q
Difference between early signs of normal aging & dementia for memory/concentration
A
- Normal: periodic minor memory lapses or forgetfulness; occasional lapses in attention
- Dementia: misplacement of important items, confusion performing simple tasks, difficulty making routine decisions, confusion about month or season
25
Difference between early signs of normal aging & dementia for mood/behavior
- Normal: temporary sadness or anxiety based on appropriate & specific cause
- Dementia: unpredictable mood & denial of symptoms
26
Difference between later signs of normal aging & dementia for language/speech
- Normal: unimpaired language skills
- Dementia: difficulty completing sentences or finding the right words
27
Difference between later signs of normal aging & dementia for movement/coordination
- Normal: slower reaction times
- Dementia: visibly impaired movement or coordination including halting gait & reduced sense of balance
28
Diagnosis of Alzhiemer disease
- Requires progressive decline form PLOF resulting from impairment in multiple cognitive domains beyond memory & which impairs daily ADLs
- Ruling out potentially reversible causes of cognitive decline
- Assessing rate & consistency of decline is helpful: abrupt changes are not consistent with AD, AD progresses very slowly
- Information from family/caregivers are also helpful
29
What reversible causes of cognitive decline need to be ruled out for diagnosis of Alzhiemer
- Multiple drug interactions
- Infections
- Dehydration
- Trauma
30
Dementia screening tests
- MMSE
- MoCA
- SLUMS
- Mini-cog
- Short Blessed test
- CDT
31
Describe the clinical dementia rating instrument
- 5 point scale used to characterize 6 domains of cognitive & functional performances
- Domains: memory, orientation, judgement & problem solving, community affairs, home & hobbies, and personal care
- Information for rating is obtained through an interview
32
What to perform for differential diagnosis of Alzhiemer disease to rule out other possible causes using lab tests
- Blood counts, Metabolic panel, Vit B12, folate levels, thyroid & liver function tests
- Urine & serum toxicology, heavy metal screens
- Chest x-ray, ECG
- Brian imaging: for volumetric measurements of entorhinal cortex, hippocampus
33
What tests should you do for biomarkers related to Alzhiemer disease for diagnosis
- CSF tau increases
- CSF B-amyloid levels decrease: Brian acts as sink
- APOE4 genetic screening
34
Diseases that can mimic Alzhiemer disease
- Pick's disease: uncommon, pick bodies seen (clumps of misfiled Tau)
- Vascular dementia: associated with series of multiple minor strokes or watershed strokes
- PD (Parkinson's disease) dementia
- Lewy body dementia: clinical findings & pathology overlap with AD/PD, Lewy bodies & plaques present
- Frontotemporal dementia: frontal lobe most affected, drastic personality changes, overlaps with Pick's disease
35
What are the 7 stages of the Global Deterioration Scale (GDS)
- Stage 1: No cognitive decline
- Stage 2: Very mild cognitive decline (age related)
- Stage 3: Mild cognitive decline (MCI)
- Stage 4: Moderate cognitive decline (mild dementia)
- Stage 5: Moderately severe cognitive decline (moderate dementia)
- Stage 6: Severe cognitive decline (moderately severe dementia)
- Stage 7: Very severe cognitive decline (serve dementia)
36
Describe stages 1-2 of the GDS
- Stage 1: no complaints of cognitive decline, no deficit evident during interview
- Stage 2: subjective complaints of memory deficits, no objective memory deficit on clinical interview or in ADLs/job/social situations
37
Describe stage 3 of the GDS
- Beginning of dementia, clear cut deficits in interview
- Getting lost when going to unfamiliar locations, functional deficits at work/social situations
- Word/name finding difficulties
- Concentration & memory deficits
- Denial begins, anxiety develops
38
Describe stage 4 of the GDS
- Clear cut deficits during interview: decreased knowledge of current events, poor historian, concentration deficits
- Decreased ability to travel, handle finances, perform complex tasks
- No deficits with: face recognition, travel to familiar locations, orientation to space/time
- Independent with basic self care, need supervision with IADLs, rigid with routine
- Safety issues
39
Describe stage 5 of the GDS
- Needs some assistance to survive on daily basis, unable to recall major close aspects of life (address, phone #, family members)
- No assistance with tolieting/eating but need it to bathe/change clothing
- Can do routine tasks like laundry but need structure
- Tunnel vision, may feel cold, can sustain task for at least a minute
40
Describe stage 6 of the GDS
- Entirely dependent for survival
- May forget spouse's name but know theirs
- Disoriented to time/place, loss of diurnal rhythm (days/nights mixed up)
- Require some assistance with ADLs, loss of fine manipulation during self care
- Poor tolerance to clothing
- Fall risk, shuffling gait, posture/balance problems, can perform transfers with assistive device
- Agitated at times, depressed, apathy, reserved from social life, wanders, psychotic behavior (delusions)
41
Describe stage 7 of the GDS
- All verbal abilities to communicate are lost, only unintelligible words, may express with grunting
- Incontinent, dependent for all ADLs including feeding, dysphagia
- Unable to walk, may have trunk movement in bed, general rigidity, primitive reflexes may appear, risk for skin breakdown/contractures
42
Treatment management for Alzhiemer disease
- No current cure
- Meds focus on inhibiting cholinesterase activity & promoting NMDA receptor activity: donezepil, Rivastigmine, memantine
- Meds to treat comorbidities
- Diet: low in fat, high in omega-3s, vegetables with Vit C, B12, folate, moderate alcohol intake
43
What important factors may delay onset or slow progression of Alzhiemer disease
- Regular physical activity
- Intellectual activity
- Social engagement
44
Describe prognosis of Alzhiemer disease
- Period of onset to death: 7-11 years
- Cause of death: dehydration, infection
45
Implications for PT
- Overall rehab strategy: recovery of function/motor learning in early stages, maintenance of function/compensation during later stages
- Dual task training increases neuroplasticity, reduces/slows cognitive loss, improves mood & behavior
- Group therapy programs: exercises with story telling periods stimulate cognitive aspects along with movement
- Increased agitation when mistakes are recognized: use appropriate feedback (KR or KP)
- Part whole practice might be helpful for complex ADL tasks
- Early stages = high level balance & gait
- Later stages = routine activités & caregiver training
46
Implications for PT in advanced stages of dementia
- Structured exercise & mobility programs
- Perform same routine daily: train functional mobility skills in structured environments with limited variability
- Exercise program should be short & spread-out throughout the day: reduces restlessness & wandering and improve sleep patterns
- Preventing loss of independence through exercise (PLIE) for 1hr 2x/wk for 12-18 wks
47
What are the therapeutic cornerstones for individuals with dementia
- Physical exercise
- Cognitive exercise
- Social exercise
