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Dementing Diseases Notes:

Neurology  Patchy distribution


Dr. Baroque  Extends beyond anatomical demarcations, distribution of lesions are
February 1, 2008 more on functional demarcations
 Location of lesions in dementias are more on subcortical location →
Dementia affects integration of command, understanding
- Syndrome of cognitive decline with variable non-cognitive - e.g. Programming in area 6 however integration occurs
features of behavioural and psychiatric symptoms and underneath
disturbances in ADL’s
- Absence/Failure of orientation Classification
- Affects cognition whether primary of secondary A. Progressive Dementia, Absent (inconspicuous) other
Notes: neurological signs:
 Primary Dementia → idiopathic e.g. AD, Parkinson’s disease 1. Diffuse Cerebral Atrophy
 Secondary Dementia → e.g. Trauma, Subdural Hematomas - Alzheimer’s Disease
 Cognition - Diffuse Lewy Body Dementia
- IQ → numerical concept of intelligence by Beni & Simon (1920) 2. Circumscribed Cerebral Atrophy
IQ = Mental Age - Pick’s Disease (Lobar Sclerosis)
Chronoligical Age - Frontotemporal Dementia
*chronological age until age 14 only B. Progressive Dementia, plus other neurological signs
- IQ increases up until age 14 only 1. Huntington’s Disease
- Only measures mathematical and language skills 2. Body Dementia
- Other types of intelligences not accounted for: musical, 3. Parkinson’s Disease → orthostatic hypotension,
visuospatial intelligence → however also affected by dementia involvement of motor movement, dementia
 Non-cognitive C. Disordered posture and movement
- Behavioural: including personality disorders 1. Parkinson’s Disease
- Psychiatric 2. Dystonia

Differential Diagnosis of Dementia Alzheimer’s Disease


Vascular Dementias 5% Epidemiology
Multi-infarct Dementia - Prevalence
Vascular Dementias and Alzheimer’s Disease 10% - 65-70: 1.5
- 70-75: doubles every 5 years
Alzheimer’s Disease 64%
- 18 million worldwide
Lewy Body variant of AD 6%
- 4 million in US and 4 million in Europe
AD and Dementia with Lewy Bodies
Dementia with Lewy Bodies 9% Risk Factors
Parkinson’s Dementia - Old age*: incidence rises sharply with age
Diffuse Lewy Body Disease - Family history*: about 1% definite genetic abnormality
Other Dementias 6% - Chromosome 21: Amyloid gene → senile plaques
Frontotemporal Dementia - Chromosome 19: ApoE4 → inherited disposition to
Corticobasal Degeneration form senile plaques and neurofibrillary tangles
Progressive Supranuclear Palsy - Chromosome 1,14: Presenelins 1 and 2
Huntington’s Disease - Low education*
Creutzfeld-Jacob Disease - Head trauma* (sustained)
 Alzheimer’s Disease increases in incidence especially among those - Hypothyroidism
>60 years old - High cholesterol
 Vascular Dementia → ischemic stroke - Metals: copper and zinc
 Frontotemporal Dementia → Pick’s disease * most important
 Creutzfeld-Jacob Disease → viral cause
 Lewy Body variant of AD → different from Lewy Dody of Clinical Features
Parkinson’s disease - Gradual development of forgetfulness is the major
symptom
Dementia 1. MCI → Mild Cognitive Impairment vs. Age-associated
- Dementia: DSM-IV Criteria memory impairment
A. Multiple Cognitive Deficits (both) - Forgetfulness with proper nouns, appointments
1. Memory impairment → intelligence (inconsistent)
2. One (or more): - No change in personality
- Aphasia → language - No disturbance in basic ADLs
- Apraxia → motor - MMSE = 24-26
- Agnosia → inability to recognize - CDR = 0.5\CT, MRI → decrease in volume
- Executive dysfunction (hypocampus, medial temporal lobe)
B. Impaired social/occupational functions  If Age-associated → usually can still recall if given
C. Gradual/progressive course → at 5-7 years effort
Notes:  MCI → if cannot remember
 Sudden onset → never AD, maybe subdural hematoma 2. Mild AD
 Common situation: - No recall of forgotten names →relatives, colleagues,
- Talks on the phone → opens faucet → slept, flooded house → friends
suspicious, paranoid - Gradual deterioration in naming → Dysnomia
 Broca’s area - Verbal fluency declines → restricted vocabulary
- 4 → motor - Forgetful for recent events, preserved remote memory
- 6 → planning frontal lobe organization - Tasks becoming routinary and simple
- 8 → horizontal gaze - Words, questions repetitive
- Connection between these areas should be intact - Minimal changes in behaviour → irritable, seclusive
- Minimal change in instrumental ADL’s
Degenerative Diseases of the Nervous System - MMSE scores: 20-24
- Selective involvement of anatomically and physiologically - CDR: 1
related neuronal systems → system atrophy - CT/MRI → beginning atrophy
- Disturbance of frontal lobe functions due to neuronal disruption
3. Moderate AD
- Severe psychiatric symptoms: depression, Transcribed by: Fred Monteverde
hallucination, aberrant motor behaviour, apathy, Notes from: Denise Zaballero
delusion, disinhibition, night-time behaviour, irritability Cecile Ong
- IADL’s disturbed Emy Onishi
- More cognitive problems: agnosia, apraxia, Pictures from: Mitzel Mata
dysexecutive syndrome
- MMSE = 10-19 Fred Monteverde
- CDR = 2 Emy Onishi
- CT/MRI → generalized atrophy Mitzel Mata
Cecile Ong
4. Severe AD Regina Luz
- Confined to home, bedridden Mae Olivarez
- Motor problems, incontinence Section C 2009
- Basic ADL’s mostly impaired e.g. walking
- MMSE = <9
- CDR = 3
- CT/MRI → severe atrophy, dilated ventricles

Pathophysiology
- Neuronal loss: cholinergic neurons in basal forebrain (N.
Basalis), entorrhinal cortex → hippocampus, amygdala →
limbic system → medial temporal lobe → association
cortices → frontal/temporal/parietal

Two Important Histologic Markers


1. Amyloid Plaques
- B-amyloid/B/A4
- Extracellular deposit
- 6-10nm fibrils
- Chromosome 21
2. Neurofibrillary Tangles
- Collection of paired helical filaments (intracellular)
- Derived from Tau protein, normal component of the
microtubule
Notes:
 Pathologies are also seen in normal individual, difference is in
quantity → about 30% more

Lobar Atrophy (Pick’s Disease)


- Atrophy circumscribed (frontal and/or temporal) cerebral
atrophy (paper thin gyri)
Histology
- Loss of neurons, most marked first 3 layers
- Pick bodies → intracytoplasmic, argentophilic bodies
(inside cell)
- Globose neurons
Clinical
- Gradual onset mental confusion (place, time), anomia,
slowed comprehension, loss tact, deterioration of work
habits, neglect of personal hygiene and grooming, apathy,
personality change
- Focal ND’s: aphasia, apraxia
- More hallucinations than AD

Lewy Body Disease


- Cortical neurons contain Lewy Bodies
- Neurofibrillary changes and senile plaques are not prominent
- Lewy Bodies → aggregated a-synuclein (related to
Parkinson’s)
- Next common form of diffuse cerebral cortical atrophy
Clinical
- Confusion, hallucination and paranoid delusion
- Psychotic symptoms → not characteristic of AD and Pick’s
- More advanced: similar to AD
Histology