Post on 15-Jan-2016
Dementia:So Far,
So Near,
Majid Barekatain, M.D.,Associate Professor of Psychiatry
NeuropsychiatristIsfahan University of Medical Sciences
27-28 Ordibehesht 1392April 16-17, 2013
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Lancet 1997; 349: 1546-49
Lancet 1997; 349: 1546-49
Prevalence of Dementia Increases with Age
3%
19%
47.20%
0%5%
10%15%20%25%30%35%40%45%50%
65 - 74 75 - 84 85 +
Age Group
Projected Prevalence of AD
16
14
12
0
2
4
6
8
10
2000 2010 2020 2030 2040 2050
4
5.86.8
8.7
11.3
14.3
Mill
ions
4.5 Million AD Cases Today—Over 14 Million Projected Within a Generation
Year
Evans DA et al. Milbank Quarterly. 1990;68:267-289.
Global Aging
Definitions
Normal
Mild Cognitive Impairment
Dementia
Dementia
• An acquired disorder of intellectual impairment produced by a dysfunctional brain
Dementia Definition
• Syndrome of acquired persistent intellectual impairment
• Persistent deficits in at least three of the following cognitive domains:
– memory– Language– Visuospatial– personality or emotional state – Higher cognition
• Resulting in impairment in Activities of Daily Living (ADL)
Mild Cognitive Impairment (MCI) Definition
• Memory complaint usually corroborated by an informant
• Objective memory impairment for age - that represents a change in function for the person
• Essentially preserved general cognitive function• Largely intact functional activities• Not demented• Alzheimer’s disease may start like this but many non-
AD conditions present like this also
Petersen J Int Med 2004;256;183-194
Rates of MCI Conversion to Dementia
• Vary from 1% - 25% per year to AD depending on the definition used and measurement instruments
• 10% - 12% per year to AD is typical• 57% conversion to dementia after 3 years
in one study• 25% do not convert to dementia even
with long term follow-upChertkow et al. Neurology 2001;56:B46
Symptoms of AD
• Cognitive symptoms include:– Memory loss and impaired temporal orientation– Impaired praxis and spatial ability– Language and executive disturbance
• Functional symptoms include:– Reduced ability to carry out IADL/ADLs, e.g.,
dressing, handling money, personal hygiene
Henderson & Jorm. In: Maj M, Sartorius N, eds. © 2000 John Wiley & Sons Ltd, Chichester, UK
• Behavioural/psychological symptoms include:• Mood swings• Agitation• Aggression• Wandering
• The type and timing of symptom expression is highly variable between patients
Henderson & Jorm. In: Maj M, Sartorius N, eds. © 2000 John Wiley & Sons Ltd, Chichester, UK
Symptoms of AD
Cognitive deficits in AD
• Memory impairment – difficulty in learning new information, and/or forgetting previously learned material
• Aphasia: impaired language function• Apraxia: the inability to perform previously learned skills in
the absence of defects in motor or sensory function• Agnosia: a failure to recognise objects, eventually
progressing to not recognising family members, or their own reflection
• Decline in executive functioning• Spatial and temporal orientation may also be affected
Mendez MF, Cummings J. Dementia. A clinical approach. 3rd ed. Philadelphia: 2003
Short Term Memory
• Short-term memory (STM)– Ability to register information– Ability to recall the registered information
• Free recall (MCI, Mild AD)• Cued recall (Mild to Moderate AD)• Recognition (Moderate AD)
Mendez MF, Cummings J. Dementia. A clinical approach. 3rd ed. Philadelphia: 2003
Long term memory
• Declarative (Moderate AD)– Concepts (semantic)
• Frontal lobe
– Events (episodic)• Cortical sensory association areas (auditory and visual)
– Words (lexical)• temporal lobe (hippocampus)
• Procedural (Severe AD)– Memory for motor tasks
• basal ganglia & motor cortex
Mendez MF, Cummings J. Dementia. A clinical approach. 3rd ed. Philadelphia: 2003
Language
• Language is the encoding/decoding of a message to communicate thoughts with words or symbols
• Language can be:– Spoken / Comprehended– Written / Read– Pictured– Gestured
Domenico RA. Adv Exp Med Biol 1990; 282:79-88
Language deficitsMild AD
• Difficulties with:– word finding/naming– abstract or complex
concepts– pronouns– storytelling– humour / sarcasm– initiating conversation– maintaining topic
• Use of:– semantic paraphasias
(substituted words)– circumlocution– empty words (it, stuff,
thing)– gesture
• Relatively intact– comprehension and
repetition
Domenico RA. Adv Exp Med Biol 1990; 282:79-88
Language deficitsModerate AD
• Decreased word fluency / vocabulary, confrontation naming
• Few ideas and frequent repeating• Poor use of pronouns• Poor pragmatics – e.g.- poor topic maintenance,
little sensitivity to conversational partners• Circumlocution increased• More difficulty with complex language
comprehension and production
Domenico RA. Adv Exp Med Biol 1990; 282:79-88
Language deficitsSevere AD
• Severely diminished naming• Exhibits more paraphasias (word and sound
substitution), echolalia (repetition of other’s speech), palilalia (rep. of own speech)
• Poor comprehension• Use of jargon and rambling speech, incoherence• Decreased eye contact• Diminished output or may be meaningless or
bizarre; may become mute
Domenico RA. Adv Exp Med Biol 1990; 282:79-88
Communication
• Broad term encompassing all the ways we send and receive messages
• Includes speaking, listening, reading, writing, gesturing, miming
• Requires a sender and a receiver
Communication
• Verbal– Words
• Non verbal– Facial expression– Eye contact– Body language– Gesture– Paralinguistics
• Intonation, loudness, pitch, rithm
Functional communication
• The ability to receive or to convey a message, regardless of the mode, to communicate effectively and independently in a given environment
• Functional communication involves also functional abilities that enable patients to make themselves understood by relatives and carers.
American Speech-Language-Hearing Association (ASHA). Functional Communication Measures Project. Rockville,MD 1990; ASHA., Domenico RA. Adv Exp Med Biol 1990; 282:79-88.
Executive Function
• Planning, (Mild to Moderate AD)• Working memory, (MCI, Mild AD)• Attention, (MCI, Mild AD)• Problem solving, (Mild to Moderate AD)• Verbal reasoning, (Moderate to Severe AD)• Inhibition, (Moderate to Severe AD)• Mental flexibility, (Mild to Moderate AD)• Task switching, (Mild to Moderate AD)• Initiation and monitoring of actions, (Moderate to
Severe AD)
Symptom progression pattern in patients with Alzheimer’s disease
Stage of Global Deterioration Scale (GDS)
Adapted from:Reisberg et al. Am J Psychiatry 1982; 139: 1136–1139
MMSE stages
• Anxiety• Misplacing objects• Forgetting names
• Unable to recall names of close family members
• Disoriented to time and place• Unable to perform complex tasks
• Basic psychomotor skills are lost• Delusional behaviour• Incontinence
Forgetting names one formerly knew well
Word and name finding deficit becomes evident
Flattening of affect and withdrawal fromchallenging situations
Difficulties dressing properly
Can no longer care for oneself
Ca
reg
ive
r bu
rde
n
6
7
Loss of speech, locomotion, consciousness; full-time care needed
2
3
4
5
Se
ve
re
<1
0M
od
era
te1
0–
19
Mil
d2
0–
26
1
0 5 10 15 20Years after onset
Progression and symptoms of AD
Pattern of symptoms over time in patients with AD
Gauthier. (Ed) Clinical Diagnosis and Management of Alzheimer’s Disease. Third Edition, Informa Healthcare
Progression of Alzheimer’s diseaseMild Severe
Det
erio
rati
on
Mood
Cognitive function
Functional autonomy
Behaviour
Motorfunction
Difficulties prompting the seeking of help: overview
Difficulties listed in order of decreasing importance
Area of difficulty:
92%87%
79%
64%
Cognition Activities of daily living
Behaviour Communication
Memory/confusion
Concentration/attention
Orientation/getting lost
Recognising people
Finding belongings
Financial activities
Shopping
Using telephone
Cooking
Personality changes
Depression
Irritability
Social withdrawal
Wandering
Following conversation
Writing/reading
Speaking
Comprehension of language
Georges et al, Int J Geriatr Psychiatry 2008; 23 (5): 546–551
Methods of Screening
Screening with Biomarkers
Biomarkers in AD• Cerebrospinal fluid (CSF) biomarkers
– Tau ( in CSF in AD)
– A42 ( in CSF in AD)
– Neural thread protein (NTP)– Homocysteine ( level, risk of AD)
– Isoprostanes (oxidative/nitrative damage - levels in blood and CSF in AD)
– Sulfatide (in CSF in AD)
• Blood and urine biomarkers– Genetic blood tests and genotyping– Plasma A42, Homocysteine, isoprostanes, sulfatide– Urine neural thread protein (NTP)
Screening with Neuroimaging
Early Diagnosis: Structural Neuroimaging
• Volumetric measurement of hippocampus and entorhinal cortex atrophy with MRI is sensitive (95%) but not specific (40%) for AD
• Change in MRI hippocampal volume may be predictive over time in both MCI and individuals at genetic risk for AD
• 7-Tesla and 8-Tesla MRI being used in AD research
Laakso et al. Neurology 1996;46:678-81Golomb et al. Neurology 1996;47:810-3
Whitaker et al. Society for Neuroscience 2001
Gray Matter Reductions in AD Using Voxel Based Morphometry
Alexander GE et al., ADNI MRI Core Team, 2007
Functional Neuroimaging: PET
• PET shows hypometabolism in bilateral parietal, temporal, and posterior cingulate cortex in AD subjects and those who are asymptomatic but at increased risk for AD (those with Apo E 4)
• PET predicted 94% of mild cognitive impairment (MCI) subjects whose disease progressed to dementia during a 3 year period
Minoshima et al. J Nucl Med 1995;36:1238-48
Minoshima et al. Ann Neurol 1997;42:85-94Small et al. JAMA 1995;273:942-47
Typical AD PET Scan
Provided courtesy of M. Mega, MD, PhD, Department of
Neurology, UCLA School of Medicine.
Normal Brain AD Brain
Cognitive Screening
Examples of Brief Cognitive Assessment/Screening Tests
• MMSE• Clock Drawing Test• Mini-Cog• AD8• 7-minute Screen• Montreal Cognitive Assessment (MoCA)• Neuropsychiatry Cognitive Assessment Tool
(NUCOG)• Self-Administered Gerocognitive Examination
(SAGE)
MMSE
• Score: 0 (worst) - 30 (best)• Tests orientation, attention, mental control,
calculations, delayed memory (no clueing), language, and constructional praxis
• Easy to use, well known• Not great for frontal or executive functions• Sensitivity 78% and specificity 84% for dementia with
a cutoff of 26/30• Takes 7 to 10 minutes; needs examiner• PAR bought rights - costs about $1 per use
Folstein et al. J Psychiat Res 1975;12:189-98Feher et al. Arch Neurol 1992;49:87-92
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Folstein et al. J Psychiat Res
1975;12: 189-98
MMSE
Mini-Mental State Examination:Typical change over time
0
5
10
15
20
25
30
0 1 2 3 4 5 6 7 8 9 10 11 12
Years since diagnosis
MMSE Score
Average change is 3 points/year without treatment between MMSE of 23 to 5
Mild Cognitive Impairment (MCI)
Clock Drawing Test
• Various scoring methods• Tests constructional praxis, visuospatial
skills, and executive functioning• Easy to use, well known• Limited in evaluating other cognitive
domains• Sensitivity 83% and specificity 72% for AD• Takes 1 minute; needs no examiner
Shulman et al. Int Geriatr Psychiatry 1986;1:135-40Cahn et al. Arch Clin Neuropsych 1996;11:529-39
Early Diagnis: Cognitive Screening
Mini-Cog
• 3-item recall and clock drawing• Easy to use• Limited in evaluating other cognitive
domains• Sensitivity 76% and specificity of 89% for
dementia• Score not influenced by language or
education• Takes 3 minutes; needs examiner
Borson S et al. Int J Geriatr Psychiatry 2000;15:1021-1027Borson S et al. JAGS 2003;51:1451-1454
Mini-Cog
AD8• Score: 0 (best) - 8 (worst)• Informant rates changes in the patient’s
judgment, interests, memory, functioning, and orientation
• Easy to use• Does not measure patient cognition• Sensitivity 84% and specificity 80% for dementia
with a cutoff of 2 or greater• Takes 3 minutes; needs examiner and informant
Folstein et al. J Psychiat Res 1975;12:189-98Feher et al. Arch Neurol 1992;49:87-92
AD8
Galvin et al. Neurology
2006;67:1942-1948
7 Minute Screen• Special scoring calculator required• Tests orientation, memory, clock drawing, verbal
fluency• Not easy to use in primary care office• Low scores very specific for AD• Sensitivity 92% and specificity 96% for AD vs normal
controls• Takes 7 - 12 minutes; needs examiner
Solomon et al. Arch Neurol 1998;55:349-55
7 Minute Screen
Montreal Cognitive Assessment (MOCA)
• Score: 0 (worst) - 30 (best)• Tests orientation, memory, clock drawing,
constructions, verbal fluency, naming, repetition, attention, abstraction, calculations, executive (trails B)
• Not easy to give in primary care office• Sensitivity 100% and specificity 87% for AD
vs normal controls with a cutoff of 26/30• Takes 10-13 minutes; needs examiner
Nasreddine et al. J Am Geriatr Soc 2005;53:695-699
MOCA
Nasreddine et al. J Am Geriatr Soc 2005;53:695-699
Self-Administered Gerocognitive Exam (SAGE)
• Score: 0 (worst) - 22 (best) • Tests orientation, memory, language, fluency,
naming, visuospatial, abstraction, calculations, executive functioning, and problem solving
• Self-administered, easy to use• Limited memory evaluation; excellent
executive measures• Takes 10 to 15 minutes; needs no examiner
Scharre et al. Alzheimer Dis Assoc Disord 2009 at sagetest.osu.edu
SAGEPage 1
Scharre et al. Alzheimer Dis Assoc
Disord 2009 at sagetest.osu.edu
SAGEPage 2
Scharre et al. Alzheimer Dis Assoc
Disord 2009 at sagetest.osu.edu
Scharre et al. Alzheimer Dis Assoc
Disord 2009 at sagetest.osu.edu
SAGEPage 3
Scharre et al. Alzheimer Dis Assoc
Disord 2009 at sagetest.osu.edu
SAGEPage 4
Staged Screening: Impact of Diagnosis
Screening for Cognitive Impairment
• No cognitive screening test is diagnostic• If normal, serious conditions are less likely• The “worried well” can be relieved that
they were “tested” and they did fine• Serial screening could be suggested over
time• If abnormal, further evaluation may be
considered
Staged Screening Approach for Cognitive Impairment
• One single test or score should not be the only criteria to embark on an expensive dementia evaluation
• Doing a screening process in stages may provide better evidence for diagnosis of MCI or dementia
• A staged screening process is recommended
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