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64 Cards in this Set
- Front
- Back
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MCI |
prodromal to AD for some pts
relatively isolated cog imp beyond that expected for normal aging
several subtypes, incl: amnestic, nonamnestic, multidomain
imp do not dramatically interfere with everyday function and therefore do not reach a clinical level to warrant Dx of dementia
requires a memory or cog complaint
deficits quantifiable- usually 1.5 SD from mean on formal mem testing (though no universally accepted psychometric criteria at this point
10% a year convert to dementia, with the amnestic subtype most commonly progressing |
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in amnestic MCI |
verbal mem usually impaired, though in some cases greater vis mem imp |
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NIA-AA research criteria on preclinical AD
earliest pathological biomarkers for AD (occur prior to clinically sig sx) |
PET amyloid imaging
accumulation of a-beta42 in the CSF
hippocampal volume loss |
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future testing |
- lesions consist of synaptic and neuronal loss assoc with progressive deposition of amyloid in the form of diffuse neuronal plaques, along with the accumulation of tau abnormalities in the form of neurofibrillary tangles and neuropil threads
- during disease progression there is cell atrophy, cell loss, and subsequent reduction in the production and sensitivity to various neurotransmitters, including choline acetyltransferase, as well as serotonin and norepinephrine
- the progression follows a temporal to frontal spread and eventually involves multiple brain systems
- hippocampus and entorhinal cortex implicated early stage of the disease, followed by frontal, temporal, and parietal assoc areas as the disease progresses
- most atrophy in temporal lobes
- primary motor, visual, auditory, and somatosensory cortices as well as aspects of subcortical structures are relatively unaffected until quite late in the disease process |
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risk factors for AD |
- age, typically over 60, is the single largest risk factor - most cases are sporadic, but having a first degree family relative increases risk - those with APOE4 genotype (on chromosome 19) have heightened risk - cardiovascular risk factors like elevated cholesterol in mild life - mod to severe TBI - Type II DM, esp if poorly controlled - Hx of chronic Maj Dep - concurrent small vessel or cerebrovascular disease(can accelerate or ind contribute) - lower educ or cog reserve |
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genes implicated in early onset familial AD |
mutation on chromosomes 1 (presenilin 3 gene), 14 (Presenilin 1 gene), and 21 (APP gene)
Chrom 21 also implicated in Downs Syndrome, and older adults with DS typically develop plaques consistent with AD |
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incidence |
studies vary but generally 5% of those over 65 have sx consistent with AD
prevalence rates double every 4-5 hours
1 in 8 adults over age 65
avg age at Dx is 74.7 years, with most Dx btwn 70-79
AA twice as likely and Latin Americans 1.5 times as likely than Caucasians to develop AD (believed to be due to inc cardiovascular risk and education/access to Healthcare)
5% of pts with AD are believed to have familial variant, which usually has early onset and more rapid decline (Sx present btwn ages 40- 60)
between 25-50% of indiv older than 85 meet criteria for AD |
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mortality |
5th leading cause of death among people 65 and older
pts die as a result of related complications of illness (aspiration, cardiovascular failure, pneumonia, decubitus ulcer |
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AD accounts for _____ % of dementia cases |
70 |
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length of illness |
5-15 years, with mean duration at 7 years |
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tends to progress slower |
when strikes older |
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early stages of AD |
insidious deficits in memory acquisition and storage
pts may be unaware of or downplay Sx (which can be helpful in diff Dx because depressed pts complain extensively)
gross personality changes are uncommon early (and may suggest FTD), progressive social withdrawal and decreased interest in hobbies and usual activities may be seen, as well as Px with sequencing and problem solving at home and at work |
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Dx |
AD pathology can only be ascertained by neuropathic exam of brain tissue, though clinical Dx is 85-90% accurate when based on comprehensive eval |
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normal aging- changes commonly observed - sensory and motor loss |
hearing is decreased in up to 70% if those over 70
decreased visual acuity, scanning efficiency, and light-dark adaptation
odor sensitivity reduced
decreased motor speed, coordination, and strength
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normal aging- changes commonly observed
- sleep patterns |
change with age night time sleep shorter and more fragmented (which may lead to inc daytime naps)
sleep onset and awakening occurs earlier |
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normal aging- changes commonly observed |
brain volume declines as reflected by increased cortical atrophy and ventricular size |
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cog abilities resistant to aging |
vocab and verbal skills reading ability macrolevel processing simple attn. and concentration basic arithmetic problem solving recognition mem and recall of the gist of a story remote memory |
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common cog changes with age |
decreased sustained and div attn less efficient and slower rates of learning new info (may require more practice, time, and rehearsal) reduced spontaneous recall of detailed info presented recently decreased cog flexibility |
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Peterson Criteria (2008) MCI |
memory complaints demonstration of abnormal memory for age (sometimes defines as 1.5 SD below norm on formal mem tests) intact general cog Fx essentially intact IADLs absence of dementia
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prevalence rates for MCI |
increase w age, occurring in at least 10% of 70- 79 YOs and 25% of 80-89 YOs
Pts with MCI who are older than 65 have a 10- 15% greater risk of developing AD
roughly 10-15% of pts with MCI progress from MCI to dementia annually
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progression from MCI to dementia |
not all pts with MCI will progress
initial severity of memory loss is most predictive of progression to AD, and the extent to which the profile of the MCI pt appears similar to AD suggests more likely progression |
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Dx of MCI |
best made based on comprehensive neurodiagnostic evaluation that includes detailed clinical Hx, neurologic exam, blood chemistry and biomarker studies, MRI, and formal NP assessment |
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PET amyloid imaging |
may be useful in the identification of AD, with posterior cingulate and parietal regions in particular demonstrating increased tracer uptake in many patients with MCI and AD
Dx accuracy in indiv cases remains a question |
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MRI and CT results |
often show increased cortical atrophy (particularly hippocampal) and ventricular enlargement
BUT in many cases are normal for age
correlation btwn degree of atrophy and level of cog imp across studies is typically in the .5-.6 range, suggesting a sig, but imperfect assoc |
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EEG |
may show diffuse slowing as the disease progresses but is often normal, particularly in the early stages |
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neuropathology of AD |
progressive deposition of amyloid in the form of diffuse neuritic plaques along with the accumulation of tau abnormalities in the form of neurofibrillary tangles and neuropil threads
cell atrophy, cell loss, subsequent reduction in production and sensitivity to neurotransmitters including choline acetyltransferase, as well as serotonin and norephineprine
temporal to frontal spread of pathology eventually involves multiple brain systems |
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Stage 1 (1-3 years) Memory impairment dysnomia anosdiaphoria |
pts typically able to function relatively independently in familiar environments, may have trouble in unfamiliar surroundings
impairment and worsening of recent memory, learning problems, declining initiative (possibly indifference, which can be misinterpreted as depression)
may start to shy away from new situations, preferring isolation or familiar routines
some individuals may not be aware of cog changes and deny px, others are aware and dep/anx in response
MRI, CT, EEG results may continue to be unremarkable, although atrophy, particularly hippocampal, and abnormal electrophysiology may be seen
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stage 2 (2-10 years) amnesia aphasia visuospatial difficulties personality and emotional changes
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may be able to Fx adequately in familiar settings and on simple overlearned tasks, but show difficulty with more complex tasks, like bill payment or balancing a checkbook
inc poor episodic memory and rapid forgetting becomes quite apparent in the context of intact remote mem
word finding deficits and slower speech patterns
sustained attn. may suffer, and they may loose train of thought in conversation
visuospatial deficits may occur, commonly topographical disorientation and poor visuocontructional ability
misplacing things more commonplace
mood changes may include guardedness or suspiciousness, as well as irritation and agitation, sometimes as a result of forgetfulness
some pts have lack of initiation misperceived as depression
later, many req asst living placements, particularly when beh px arise and become difficult to manage
MRI results show incr sulcal enlargement and ventricular dilation
PET/SPECT results often reveal bilateral parietal hypometabolism/hypoperfusion
EEG results may show diffuse slowing of background rhythm
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Stage 3 (8-12 years) severe dementia global aphasia mutism |
profound cog imp in all aspects of cognition 24 hour supervision, dependent for all aspects of care
sleep disturbance and beh abnormalities may develop, incl hallucinations and nighttime wandering
MRI/CT results show progressive atrophy in most cases, and EEG reveals global diffuse slowing
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Stage 4 severe dementia and complete dependence |
disoriented and can no longer follow simple routines
psychotic Sx (hallucinations) may emerge
inc sedentary and may become incontinent
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Stage 5 severe disability |
may be unable to chew and swallow and uncommunicative
bedridden typically- leads to progressive muscle wasting and weight loss prior to death
inc vulnerability to pneumonia and other illnesses |
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rule outs |
Vascular dementia Lewy Body Disease frontotemporal dementia parkinsons disease other less common forms of dementia (NPH) delirium |
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delirium |
can occur due to causes such as UTI, medication effects, metabolic issues
stabilize pt prior to NP assessment |
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consider VaD |
if pts have - rapid onset - stepwise progression - sx occurred within 3 weeks of identified CVA
Contrary to previous guidelines, VaD does not always present in stepwise fashion and VaD and AD pathology often co-exist |
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Consider FTD |
if personality or beh changes are most prominent early
frontal variant- beh changes most common
temporal variant- semantic knowledge and disturbances in language |
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AD and LBD |
difficult to distinguish clinically BUT
mild memory deficits with more prominent visuospatial impairment, and other clinical features like extrapyramidal symptoms, vis hall, REM sleep beh disorder, and/or fluctuating Sx may suggest LBD |
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NP assessment |
most sensitive for detection of MCI and early AD
tests of declarative/episodic mem (verbal learning and recall), lang (conf naming, COWA), and EF have demonstrated greatest sensitivity in differentiating AD from normal aging and other forms of dementia
MSE and brief testing often miss early AD and MCI
standard neuro exam, MRI, CT, ApoE, and other lab tests have not outperformed Dx predictive accuracy of NP tests
remains only way to characterize cog strengths and weaknesses
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blood based biomarkers |
show promise in terms of sensitivity and specificity |
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Intelligence |
pts often score normally on crystalized cog abilities (sight word reading, vocab) during early stages
more basic reading ability and vocab decline at later stages |
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attn./concentration |
may display early px with divided attn. and complex concentration
general alertness and basic attn. (digits forward) remain relatively intact until mid to late stages |
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language |
word finding px and dysnomia semantic errors on confrontation task
aphasia obvious as disease progresses (mid to late stages)
Echolalia and mutism in late stages
certain variants of FTD (PPA) more prominent
language deficits, more intact episodic memory |
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visuospatial abilities |
some pts have early impairment in topographical orientation, spatial perception, and design copy tasks
visual attn. and scanning/visual discrimination remain intact until mid to late stages |
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memory |
episodic mem imp first observable Sx limited learning rapid forgetting intrusion errors on recall heightened recency effect impaired recognition
delayed verbal recall is the most sensitive
decline further delineated by greater anterograde than retrograde memory loss and greater explicit than implicit learning impairment
retrograde memory loss will develop and has a temporal gradient
remote autobiographical info remains intact into later stages
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EF |
Px with mental flexibility, reasoning, and judgment are common
Pts often lack insight into severity and impact of cog and functional decline
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sensorimotor Fx |
may decline in later stages typically only after memory and Exec dysfunction are more promounced ideomotor apraxia may occur in mid to late stages- can be seen earlier limb rigidity can occur in the late stages- as opposed to early in parkinsonian syndromes |
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emotions and personality |
changes in personality typically become an issue in the mid to late stages
pts may lack initiation which can be misperceived as depression
anxiety, suspiciousness, and/or irritability may develop, which can increase caregiver distress
hallucinations, paranoia, suspiciousness of loved ones/caregivers, and delusions occur w high freq in later stages |
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level of supervision |
minimal during MCI and early AD stages- often continue to drive, manage ADLs, and Fx independently
steadily require more supervision or attendant care with disease progression |
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Fx Issues |
to meet criteria for dementia Dx, there must be evidence of Fx decline
rate and type of Fx decline can vary considerably
Fx decline may manifest in work first, followed by hobbies, then other daily activities
routine, overlearned tasks remain more intact and may help to hide insidious functional decline
can use test like TFLS to test IADLs |
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REHAB CONSIDERATIONS |
pts req stepwise increases in monitoring and assistance for collaterals as the disease progresses
environmental management and compensatory strategies can help them stay in the home longer
regular routine, healthy diet
physical exercise may be beneficial
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driving |
driving safely may continue through MCI and the early stages of AD
Assessment of driving skills may be indicated as mem imp, visuospatial difficulties, and slowed reaction times worsen
restrictions to driving in daylight to familiar locations may be advisable, depending on deficits
as sx progress, periodic on the road driving assessments are recommended
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employment |
those with MCI and early stage AD may continue to work, though incr assistance and transition to retirement or long term disability typically becomes necessary with greater cog deterioration |
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capacity |
many pts retain capacity to participate in medical and financial decision making early in the illness
the ability to make complex decisions limited by mem impairment and exec fx deficits characteristic of mid and late stages
rec for conservator/guardian may be needed |
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emotional and psychological issues |
early in the course of AD, initiation Px may be perceived as depression
family often reports incr social isolation and less interactive style
paranoia and anx quite common, in part due to mem imp and lack of deficit awareness
in pts with depression- note tricyclic antidepressants can worsen memory |
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severe psych complications |
hallucinations and delusions (usually paranoid) may emerge in later stages of AD, occurring in 50% of cases
Sundowning may occur related to acute or chronic issues assoc with AD
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medications |
early treatment may slow disease progression
most experience continued progression
acetylcholinesterase inhibitors, like donezapil, rivastigmine, and galantamine can be used for all stages of AD
memantine (NMDA receptor agonists) typically introduced at moderate stages
no way to determine who will respond to medications and who won't
medications have demonstrated moderate effect of stabilizing and delaying disease progression 12-18 months or more for small percentage of pts
combinations of meds may have greater effect for some pts
side effects include nausea, vomiting, diarrhea, and dizziness- tolerance to side effects often develops |
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anosdiaphoria |
inability to fully appreciate the significance of a medical or neurological condition, though pt is aware of condition |
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anterograde amnesia |
looses ability to transfer new info to long term memory |
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APOE4 |
APOE combines with fats (lipids) in the body to form molecules called low density lipoproteins (LDLs)
people who inherit 1 copy have incr chance for disease. 2 copies- even greater risk
may be a protective aspect of APOE 2 and 3
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APOE2 |
people w APOE2 have biomarker signatures with less AD pathology, lower hippocampal atrophy rates, and slower rates of cog decline |
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neuritic plaques |
extracellular deposits of amyloid that consist of beta amyloid protein mixed with branches of dying nerve cells. found in the brain of people w AD
Presence of these plaques and tangles used to Dx AD at autopsy
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neurofibrillary tangles |
insoluble twisted fibers found inside brains cells that consist of a protein called Tau
forms part of a microtubule, a cellular structure that transports nutrients and other important substances from one part of a nerve cell to another
in AD TAU PROTEIN IS ABNORMAL AND MICROTABULE STRUCTURES COLLAPse |
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Tau abnormalities |
microtubule assoc tau protein is situation on Chromosome 17 and serves to stabilize microtubules
abnormal phosphorylation of tau protein destabilizes microtubules, which causes degenerative changes
pathological tau occurs in a wide range of disorders called taupathies: Familial FTP dementia with parkinsonism, PSP, corticobasal degeneration, PD, and AD |
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amyloid |
protein fragments that the body produces normally
in healthy brains, broken down and eliminated
IN AD, fragments accumulate to form hard, insoluable plaques
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amyloid hypothesis |
regarding sits causative role in AS is dominant in the field, though whether amyloid is a cause or a by product of the disease is a question |
