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Early Alzheimer's Disease and Mild Cognitive Impairment
Transcript of Early Alzheimer's Disease and Mild Cognitive Impairment
and Pera Phanichayakarn
Early Alzheimer's Disease
and Mild Cognitive Impairment
*Overview, Criterion, and Controversy
Outline of Presentation
*"...characterized by inexorably progressive degenerative nerve cell changes within the cerebral hemispheres with concomitant progressive global deterioration of intellect and personality." (Lezak et al., 2012).
* 80% of dementia is caused by Alzheimer's disease. (Lezak et al., 2012).
Overview of Alzheimer's Disease
*Definitive diagnoses can currently only be made via biopsy or autopsy, thus clinical diagnoses are commonly made be “probable” or “possible” Alzheimer’s Disease (Lezak et al., 2012).
*Although with neuroimaging improvements, a definite diagnosis while patients are alive may be in the near future (NIA, 2012).
Diagnosing Alzheimer's Disease
A. The development of multiple cognitive deficits manifested by both:
1. Memory impairments (impaired ability to learn new information or to recall previously learned information).
2. One or more of the following cognitive disturbances:
a. aphasia (language distrubances)
b. apraxia (impaired ability to carry out motor activity despite intact motor function)
c. agnosia (failure to recognize or identify objects despite sensory function)
d. disturbance in executive functioning (i.e., planning, organizing, sequencing, and abstracting)
B. The cognitive deficits in Criteria Al and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits in Criteria Al and A2 are not due to any of following:
(1) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
(2) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
(3) substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium
F. The disturbance is not better accounted for by another Axis I disorder (e.g., Major Depressive Disorder, Schizophrenia).
DSM-IV Criteria for Alzheimer's Disease
*MCI can be the transitional state from unimpaired cogntive functioning to developing Alzheimer’s Disease (Petersen et al., 1999).
*Lezak and colleagues (2012) highlight out two points of debate:
Patients diagnosed with MCI do not always progress to AD
Blurred distinction between MCI and AD
For NIH Diagnostic Criteria:
1. Concern regarding a change in cognition Subjective cognitive complaints:
Patient report, Informant (also corroborative), skilled clinician observation
2. Impairment in one or more cognitive domains Abnormal function for age and educational background
3. Preservation of independence in functional abilities Generally maintain independence of function in daily life with minimal aids or assistance
4. Absence of dementia Subtypes:
-Amnestic, single domain
-Amnestic, multiple domains
-Non-amnestic, single domain
-Non-amnestic, multiple domains
Criteria for Mild Cognitive Impairment
Hallmark changes of AD (Lezak et al., 2012):
Medial Temporal areas
Nucleus of Basalis of Meynert
Locus Coeruleus and Raphe Nucleus
Early Changes in the Brain
Episodic Memory Loss
Episodic memory is the “hallmark of the early manifestation of AD” such as MCI (Jouber et al., 2008, p. 35)
MCI can have vascular burden or not
Study (Villeneuve et al., 2008):
To compare the episodic memory deficits of individuals with MCI with and without vascular burden
Free recall and temporal contextual memory tests requiring self-initiated retrieval were used to measure strategic memory
A five-choice recognition procedure was used to measure nonstrategic memory.
Individuals who have high vascular burden
impairment in only strategic memory processes (free recall and temporal contextual memory)
Individuals with no vascular burden
impairment in both strategic and nonstrategic memory (recognition).
Thus, the presence of vascular burden results in differing episodic memory loss presentations.
Joubert, Felician, Barbeau, Didic, Poncet, and Ceccaldi, 2008; Villeneuve, Massoud, Bocti, Gauthier, Belleville, 2011
Semantic Memory Loss
Semantic memory deficits have also been associated with MCI.
Study (Joubert et al., 2008)
Method: A battery of tests that assess a variety of aspects of conceptual knowledge,
Results: Found that amnestic MCI experience difficulty with all areas of semantic memory.
The authors noted that knowledge about famous people and famous events was more greatly effected than knowledge about objects.
No difficulty was present with visuoperceptual skills.
No difficulty was present with processing complex visual material.
Joubert, Felician, Barbeau, Didic, Poncet, & Ceccaldi, 2008
Semantic Fluency Impairment
Semantic fluency impairment has been associated with MCI
Study: (Murphy et al., 2006)
Method: Sound (Letter F) and word (Animals) fluency trials
Results: Individuals with amnestic MCI ( a subtype of MCI) showed a decline in semantic fluency (as compared with phonemic fluency).
It was hypothesized that this difference results from the fact that semantic fluency relies on to a greater extent on “semantic associations between exemplars of subcategories” than phonemic fluency (p. 573).
These individuals performed significantly better on both semantic and phonemic fluency than individuals with AD.
Murphy, Rich, & Troyer, 2006
Area of Debate: More than Memory Loss and Naming Impairment?
MCI = challenges with memory tasks and naming tasks like individuals with Alzheimer’s Disease.
According to Petersen et al. (1999), individuals with MCI experience normal cognition
However, some research has shown that individuals with MCI experience cognitive impairments beyond memory loss and naming tasks
Bachman et al., 2005; Petersen, Smith, Waring, et al.,1999; Lonie et al., 2008
Attention and Executive Functioning Impairment
Both attention and executive functioning impairment has also been associated with MCI
Study (Lonie et al., 2008)
Hopkins Verbal Learning Test (verbal episodic memory),
CANTAB Paired Associate Learning (PAL) test and the Rey Complex Figure Test (Visual memory),
Graded Naming Test, the Boston Naming Test, and the Edinburgeh Exemplar Naming Test (EENT) (Semantic memory )
Using both a letter fluency task and part A and B of the Trail Making Test (Attention and Executive Functioning)
Impaired verbal episodic memory, visual memory, and semantic memory
But also, attention and executive function deficits were found.
Thus, other deficits were found beyond memory and naming.
This provides support to the idea that individuals with amnestic MCI experience multiple cognitive deficits.
Lonie, Hermann, Donaghey, Ebmeier, 2008
…And Processing Speed
Meta-analysis of preclinical Alzheimer’s Disease (MCI)
Conducted to determine impairment across multiple cognitive domains
Method: Analyzed 47 studies
Results: Marked preclinical deficits (large effect sizes) were found not only on episodic memory and executive functioning, but also perceptual processing speed
Thus, deficits of processing speed appear to be an integral part of the MCI cognitive pattern
Bachman, Jones, Berger, Laukka, & Small, 2005
Summary of Cognitive Patterns
Cognitive impairment in the areas of:
presence of vascular burden results in differing episodic memory loss presentations.
Although debated, research has also shown impairment in the areas of:
Helps to characterize the extent of cognitive impairment
Distinguish among the types of dementias
Establish baseline cognitive function
Identify strengths and weaknesses
Guide expectations for the patient
Direct interventions to improve overall function
Assist with communication
Inform capacity determinations
APA on Neuropsychological Testing
(Specifically for MCI)
Serial assessment preferable
Can help to evaluate progression (or lack of) of cognitive deficits
Can provide support for clinical observation, patient/informant report
Can assist in delineating specific MCI subtypes
Can assist in differentiation of MCI from normal aging, dementia, and depression
Careful Assessment/Testing Important
Superior intelligence at baseline may obscure the detection of cognitive deficits
Assessing for MCI
MCI/Alzheimer’s: Functional Domains and Testing
Premorbid baseline important for gauging the significance of obtained test results
Can be inferred on the basis of performance on “hold” tests that tend to be resistant to general cognitive decline
Tests of word knowledge and word recognition
WAIS – Vocabulary Subtest
Wechsler Test of Adult Reading
Nelson-Denny Reading Test – Vocabulary Section
Global Cognitive Function
Evaluations typically include one or more composite or global measures of cognitive function
Mini-Mental Status Exam (MMSE)
Dementia Rating Scale (DRS)
St. Louis University Mental Status Exam (SLUMS)
Functions of screening
Brief overview of functioning in terms of basic attention, memory, language, and spatial-constructional skills.
Quickly grade cognitive state and monitor progression of cognitive change.
Includes attention span, sustained attention, and processing speed
Deficits may not be as evident in early stages
Simple attention span may remain near normal
EX: Severely impaired patients may still be able to repeat five digits
Deficits in dividing and shifting attention may be earliest indicators
Attentional impairment is nonspecific
Deficits on tasks of attention not necessarily indicative of dementia or MCI
Predictor of competency
Trails A discriminated competent vs. non-competent P’s
accuracy ranging from 77% to 82%
Aspects of EF critical for social competence and effective behavior compromised early in course of disease
Executive Functions Include: Selective attention, capacity to resist interference, initiation/inhibition, cognitive flexibility, decision making, planning, and capacity for abstract thinking
Memory and Learning
Memory problems show up early in course of disease
Particularly Verbal memory deficits
Poor performance on tests of free recall and rote learning
Episodic memory (the ability to learn and retain new information)
Impairment most distinguishing cognitive feature of AD
Tests of episodic memory may be useful for identifying MCI patients with high likelihood of progressing to AD dementia within a few years
Ask questions focusing on temporal and spatial orientation and reason for referral
Compromised temporal orientation and knowledge of current events may be present
Unlikely to be first symptom
May remain intact even after other functions compromised
Temporal: Day of month, year, month, day of week, season
Spatial: Name of hospital, floor, town, country, state
Found to better tap into breadth of cognitive impairment
Look beyond a total score (i.e. MMSE score)
Examine pattern of performance across items
Deterioration of language ability characteristic of AD patients in early stages and ultimately all AD patients
Encompasses written and spoken language
Observation of conversational speech
Fluency, prosody, sponteniety
Note word finding difficulties
Can informally assess language comprehension
Spatial and Constructional Function and Praxis
Visuospatial function tends to be impaired in AD patients
Complex visuoperceptual discrimination difficult
Impaired ability to mentally rotate spatial images
Unilateral visuospatial inattention common
Left sided inattention most common in AD
Visualperceptual deficits common
Prominent on tests requiring visual discrimination, analysis, and spatial judgments
May be evident by impairment in pantomiming and copying gestural patterns
Ask patient to show how they would:
Hammer a nail
Unlock door, etc.
Other Sensorimotor Functioning
Typically impaired early in disease course
Research suggests predictive validity of olfactory identification tests
University of Pennsylvania Smell Identification Test (UPSIT)
Scratch and Sniff Identification
Mood, Personality, and Psychosocial Behavior
Disinterest and passivity prominent behavioral features
Apathy may be mistaken for depression
Testing can help differentiate
Anxiety, depression, psychotic symptoms, sleep disorder, frequently associated with AD
Suspicion and paranoia affect thinking of many AD patients
Specific tests may be chosen on basis of specific presentation
Beck Depression Inventory-2
Geriatric Depression Scale
Beck Anxiety Inventory
Neuropsychiatric Inventory Questionnaire
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Devanand, D.P., Pradhaban, G., Liu, X., et al., (2007). Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer’s Disease. Neurology, 68, 199-128.
Devanand, D.P., Liu, X., Brown, P.J., Huey, E.D., Stern, Y., & Pelton, G.H.(2012). A Two-Study Comparison of Clnical and MRI Markers of Transition from Mild Cognitive Impairment to Alzheimer’s Disease. International Journal of Alzheimer’s Disease, 2012, 1-8. doi: 10.1155/2012/483469.
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Can be used to assess:
Possible field cuts
Benton Judgment of Line Orientation Test
Assesses perception of angular displacement of lines
Line orientation judgment tends to be impaired
Performance can range from total failure to overlap with low performing elderly
Clock Drawing Task
Assesses visuoconstruction ability
Well documented “defective” performance
Often misplaced or omission of minute hand
Caution: Clock drawing deficits not specific to AD (Parkinson’s, Lewy Body Dementia)
Rey Complex Figure Test (RCFT)
Can be used to assess visuoconstruction ability
Segmented approach/no reference to the overall template Vs. thoughtful/well organized approach
Indicative of poor visual organization
frontal or right hemisphere impairment
May exhibit “closing-in phenomenon”
Drawing or construction close to, connected to model, or overlapping into it
May help to differentiate between AD dementia and dementia due to vascular disease
Spatial and Constructional Function and Praxis Tests
Boston Naming Test
Assesses confrontation naming (ability to retrieve words)
Controlled Oral Word Association Test (COWAT)
Assesses speed of word retrieval
Cognitively intact individuals (most): produce more words to category as opposed to letter cues
Disproportionate deficit in category generation may indicate deterioration of semantic/language systems (as seen in MCI or early dementia)
Boston Diagnostic Aphasia Examination, Token Test
Can be used to assess language comprehension
Writing sample can be used to examine problems with mechanics of writing or grammatical aspects of written language
WMS-R – Logical Memory Story A
Can be used to assess *verbal memory*
May have more ecological validity
Real world/everyday functioning
California Verbal Learning Test (CVLT)
Comparison of immediate and delayed recall yields information about rate of forgetting or retention
Comparison of delayed recall versus delayed recognition yields information regarding retrieval
Intact recognition with impaired recall suggests information has been retained but individual is unable to retrieve it without cues
Rey Complex Figure Test and Recognition Trial (RCFT)
Can be used to assess visual memory
Verbal vs. Visual Memory
Verbal < Visual memory impairment: Suggests lateralized right temporal dysfunction
Verbal > Visual memory impairment: Suggests lateralized left temporal dysfunction
Memory and Language Tests
Stroop Color-Word Interference Test
Can be used to assess inhibition and selective attention
Can be used to assess mental flexibility
Wisconsin Card Sorting Test
Is a more complex measure of EF
May occur with moderate dementia
Executive Functioning Tests
Digit Span Forward
Trail Making Test
Trails A Sustained attention
Trails B Divided attention
Slowness may be apparent on these tasks (processing speed)
Variation in type and range of attentional deficits