Degenerative Disorders:

Dementia
Marcos C.S. Ong, M.D., FPNA
 Degenerative Diseases
 General Clinical Characteristics
 Begin insidiously, after a long period of
normal nervous system function
 Ceaselessly progressive course
 Bilateral symmetry of clinical manifestations
 Familial occurrence
 Degenerative Diseases
 General Pathologic Features
 Selective involvement of anatomically and
physiologically related systems of neurons
 “System strophy”
 “Systemic neuronal atrophy”

 Disappearance/wasting of neurons
unaccompanied by any intense tissue recation
 CSF shows little, if any change
 Radiologic examshows either no change or
volumetric reduction (atrophy) with corresponding
increase of CSF compartments
 Degenerative Disorders
 Classified according to
 Specific parts of the nervous system affected
 Clinical manifestations
 “System degenerations”
 Propensity to affect only parts of the nervous system
 Progressive Dementia Progressive Dementia with
e.g. Alzheimer’s disease Other neurological features
e.g. Huntington’s disease
Progressive blindness
e.g. Leber’s optic Progressive deafness
Neuropathy e.g. Pure sensorimueral
Retinitis pigmentosa Deafness
Sensorineural defaness
with other neuro features
Progressive ataxia
Cerebellar: Holmes
Spinal: Friedrich’s Progressive movement
Disorder
e.g. Parkinson’s disease
Progressive limb weakness
+/- sensory involvement Progressive limb weakness/
e.g. Hereditary neuropathies Bulbar weakness
-Charcot Marie Tooth e.g. Motor neuron disease
- Dejerine Sotas Spinal muscular atrophy
- Refsum’s
Diseases characterized
mainly by progressive
Dementia
 Alzheimer Diseases
 Most common and important degenerative
disease of the brain
 Increasing incidence with advancing age
 Unknown cause
 Familial occurrence in <1% of cases
 Autosomal dominant inheritance
 Alzheimer Disease
Putative Pathogenesis
Usually sporadic
 Genetic Linked to Chromosome
21, 14 and 19
 Role of beta-amyloid

 Neurochemical Abnormal accumulation

Deposited in neuritic
 Toxic
plaques
Role of excitotoxic
Neurotransmitters: Depletion of Acetylcholiineesterase
Glutamate and Degeneration of Nucleus Basalis
Aspartate of Meynert
 Alzheimer Disease
 Early manifestations
 Gradual development of forgetfulness and
related neurologic function
 Day-to-day events, names, misplaced objects
 Questions are repeated again and again

 Halting speech due to inability to recall words

(anomic aphasia)
 Echolalia

 Deterioration in arithmetic skills (dyscalculia)

 How to use common objects (apraxia)

 Alzheimer Disease
 Early manifestations
 Anxieties and phobias may emerge
 Disturbance of normal day and night sleep
pattern
 Gait disturbances
 Alzheimer Disease
 Late manifestations
 social graces are lost
 psychosis with paranoia
 seizures in some
 extrapyramidal rigidity and bradykinesia

Evolution of symptoms may span 5 years or more

 Alzheimer Disease
 Terminal manifestations
 mutism, incontinence
 bedridden
 death in 5-10 years since onset
 Alzheimer Disease
 Pathology
 Atrophic process involving the
frontal, temporal and parietal
lobes
 Extreme atrophy of the
hippocampus
 Widespread loss of nerve
cells in the cerebral cortex
 Alzheimer Disease
 Pathology
 Neurofibrillary tangles
within the cytoplasm
 Senile plaques /
Amyloid plaques
 Granulovacuolar
degeneration of
neurons
 Alzheimer Disease
Investigative Studies:
 very minimal utility

 does not help in diagnosis

except to exclude other
diseases
 CT/MRI
 cortical atrophy and enlarged
ventricles which are nonspecific
 Alzheimer Disease
 Mini-mental Status Exam
 Important screening test for dementia
 Should be done in patients above 50 or
patients with complaint of memory changes
 Alzheimer Disease
Differential Diagnosis:
 Early dementia
 Depression
 Korsakoff’s amnestic syndrome
 More advanced Dementia
 Multi-infarct dementia/ Vascular Dementia
 Multiple cortical strokes may cause increasing
deficits which cumulatively qualify as dementia
 Stewise progression of deficits
 Alzheimer Disease
Differential Diagnosis:
 CJD
 prominent myoclonus, cerebellar signs,
corticospinal signs and visual disturbances
 characteristic periodic complexes in EEG
 Rapidly progressive course (6-18 months)
 Alzheimer Disease
Treatment:
 no treatment available to reverse existing
deficits or arrest the disease progression
 Cholinergic replacement therapy
 Acetylcholineesterase inhibitors
 Donepezil, Rivastigmine,Gallantamine
 May prolong patient’s functional state

 NMDA receptor antagonist

 Memantine
 Alzheimer Disease
Prognosis:
 Early Alzheimer’s
 can still engage in social, professional
activities
 Late Alzheimer’s
 requires nursing care, psychiatric medications,
and protection from harm
 death in 5-10 years
 Lobar Atrophy (Pick’s Disease)
 Circumscribed atrophy
(frontal and/or
temporal)
 Involvement of both
gray and white matter
 Affected gyri become
paper-thin and may
come to resemble a
dried walnut
 Pick Disease
 Pathologic Features
 Loss of neurons particularly in the first three
layers of the cerebral cortex
 Surviving neurons are swollen and contain
argentophilic bodies (Pick bodies) in the
cytoplasm
 Pick’s Disease
 Clinical Features
 May be clinically indistinguishable from
Alzheimer Dse
 Earlier onset and more prominent
 Personality changes
 Focal disturbances:
 aphasia & apraxia (left frontotemporal lobe)
 Apathy, abulia, gait impairment (frontal lobe)
 Frontotemporal Dementia
 Any dementia that is associated with
degeneration of the frontal and temporal
lobes
 Pathologic changes different from Pick and
Alzheimer Dse
 No Pick bodies
 Tau-staining protein in the cytoplasm of
affected neurons
 White matter not affected
 Lewy Body Disease
 Dementia clinically indistinguishable from
Alzheimer
 Progressive dementia in an elderly patient
with late-onset Parkinsonian signs
 Bradykinesia, rigidity, tremors
 Cortical neurons contain Lewy bodies
 Contains aggregated synuclein
 Also found in Parkinson Disease
 Dementia
 Syndrome of progressive deterioration in
intellectual and social abilities
 To a sufficient degree that it interferes with
the person’s social and occupational
functioning
 Many possible etiologies
 DSM IV Criteria
 Loss of intellectual abilities of sufficient severity
to interfere with social or occupational
functioning
 Memory impairment
 At least one of the following
 Impairment in abstract thinking
 Impaired judegment
 Other disturbances of higher cortical function such as
apraxia, aphasia, agnosia, constructional ability
 Personality changes
 DSM IV Criteria
 State if consciousness not clouded
 not in delirium
 Either a or b
a. Evidence of a specific organic factor that is
judged to be etiologically related to the
distrubnace
b. In the absence of such evidence, an organic
factor can be assumed if other conditions of
organic mental disorders have been
excluded
 The Burden of Dementia
 Dementia is a serious and growing
medical, social and economic problem

 Alzheimer disease and related dementias

exact a massive toll in health care costs,
disability and lost productivity of both
patients and family caregivers
 The Burden of Dementia
 Early symptoms of dementia are
commonly overlooked, mistakenly
attributed to normal aging, or
misdiagnosed

 Failure to diagnose early-stage dementia

can result in needless and possibly
harmful treatment
 Dementia: Etiology
 Degenerative  Vascular
 Alzheimer’s disease
 Multi-infarct
 Pick’s disease  Binswanger’s disease
 Huntington’s disease  CNS vasculitis
 Frontotemporal
 Subdural hematoma
dementia
 Lewy body disease
 Progressive
supranuclear palsy
 Parkinson’s disease
 Dementia: Etiology
 Metabolic  Toxic
 Thyroid disease
 Parathyroid disease
 Hepatic
encephalopathy
 Cushing’s disease
 Uremia
 Porphyria
 Vit B12 deficiency
 Anticholinergic drugs
 Antihistaminic drugs
 Drug combinations in
therapeutic range
 Alcohol
 Heavy metals, arsenic,
lead, mercury
 Dementia: Etiology
 Infectious  Neoplasm
 Chronic meningitis  Trauma
 Lyme disease  Hydrocephalus
 AIDS dementia
complex
 Inflammatory
 Herpes encephalitis  Demeylinating
 CJD  lupus
 Initial Assessment
 Focused history
 Establish the mode of onset of symptoms
 Abrupt vs gradual
 Progression of symptoms
 Stepwise vs continuous decline
 Worsening vs. fluctuating vs. improving

 Duration of symptoms
 Initial Assessment
 Focused physical and neurological
examination
 Assess for conditions that cause delirium
 Signs of abuse and neglect
 Informant reports
 Information obtained from family members
and caregivers
 Consider questionable motives of informant reports
 Initial Assessment
 Brief mental status tests
 Used to develop a multidimensional clinical picture
 Provide a baseline for monitoring the course of
cognitive impairment over time
 Reassess mental status in persons who have
treatable delirium or depression on initial
evaluation
 Document multiple cognitive impairments as
required for a diagnosis of dementia
 (MMSE) Mini-Mental Status Examination
 Widely recognized instrument for the
detection of cognitive impairment
 Sensitivity of 49%
 Specificity of 92%
 (CDT) Clock Drawing Test
 Scores are based on the patient’s ability to
properly draw the face of a clock by the
appropriate placement of numbers and the
hands of a clock to the designated time
 Neuropsychological testing
 Adjunct to the neurological and mental
status exam
 Provides precise quantitation of various
cognitive functions
 Determine whether any impairment exists
 Profile the defects
 Identify extent of involvement
 Provide a baseline for future assessment
 Assessing for Depression
 Depression
 May be difficult to distinguish from dementia
 May coexist with dementia
 Most common psychiatric illness in older
persons
 Assessing for Depression
 Depression  Dementia
 Changes in memory,  Marked visuospatial or
attention language impairment
 Changes in the ability
to make and carty our
plans
 Final Diagnosis
 Clinical judgment based on history from
the patient, family, neurological and
medical examination and
neuropsychological tests
 Salient feature is a CHANGE in intellectual
and social function
Mild Cognitive Impairment (MCI)
 Refers to the state of cognition and
functional ability between normal aging
and very mild Alheimers Disease
 Higher risk of progressing to dementia or
Alzheimer’s disease
 0.2% in the 65-69 age range
 3.9% in the 85-89 age range
 Rate of progression to dementia is 6 and 25%
per year
 MCI Criteria
 Memory complaint, preferably
corroborated by an informant
 Objective memory impairment
 Normal general cognitive function
 Intact activities of daily living
 Not demented
 Mild Cognitive Impairment
 Practice recommendation
 Patients with mild cognitive impairment
should be monitored for cognitive and
functional decline due to their increased risk
for subsequent dementia
 The Importance of Follow-up
 May be the most useful diagnostic
procedure for differentiating AD from
normal aging
 Repeat mental status tests over a period
of 6-12 months