Dementia – BRAIN

Characteristics

Term has been used since 1800’s
Loss of function in multiple cognitive abilities
(According to DSM diagnosis) Does NOT imply specific underlying cause, progressive course, OR irreversibility (it can be static, progressive or remitting)
Distinction b/t delirium and dementia can be difficult (frequently may coexist)

Some definitions do require persistence in order to exclude acute traumatic, metabolic, or toxic disorders

DSM-IV Diagnosis requires memory impairment AND at least one kind of cognitive deficit (e.g., aphasia, apraxia, agnosia, executive function) ~ thereby distinguishing it from simple amnesia or aphasia

Deficit must cause problems in occupational or social functioning
Must be a decline from higher level of functioning
Not occur exclusively during delirium
DAT dx adds:
- Course is characterized by gradual onset and continuing cognitive decline
- Disturbance not better accounted for by another Axis I or medical disorder
Disadvantages of DSM definition
- Excludes patients with persevered memory (e.g. Pick’s)
- Requirement for social/occupational disability renders definition imprecise

Onset

Depends on etiology – but generally happens late in life
Uncommon in children but may occur as a result of a general medical condition

Prevalence

approximately 5% of individuals >65 are severely demented and 10-15% are mildly impaired
prevalence increases with age  20% or more of population are demented by age 85
presenile dementia – when re-examined 1-15 years later 25-57% failed to deteriorate in expected manner; believed due to unrecognized depression
Alzheimer’s most common, followed by vascular dementia (many patients have both)

Evaluation

detailed history – assess for inherited types of dementia
evaluate for depression, hysteria, or psychosis
explore medical history for strokes, seizures, TBI, alcohol/drug abuse, AIDS, endocrine dysfunction, vitamin deficiency (B12) and cancer
Neurological exam and comprehensive evaluation of cognitive skills

Cortical Dementias

Alzheimer’s Disease

(Dementia of the Alzheimer’s Type – DAT) loss of cholinergic neurons in the nucleus basalis of Meynert leading to development of senile plaques and neurofibrillary tangles

characterized by marked deficits in memory, language and perception. Can also have symptoms of depression (quite common)

Epidemiology

onset – between 40 and 90 years and becomes increasingly common w/advancing age; most commonly seen after age 65
- affects 5-10% of people over 65
risk factors – female, family history of down syndrome, TBI and history of thyroid disease
diagnosis – typically a matter of exclusion; w/c makes it a catch all for all unrecognized dementias and renders DAT a nonspecific diagnosis; definitive dx can only made on autopsy

Neuropathologic features

The primary motor, somatosensory, visual, and auditory cortices are relatively spared See Figure 19.14 on page 873 for a visual depiction.

Progression

The following areas are generally affected first (and later, more severely). Listed in decreasing order:

medial temporal lobes, including amygdala, hippocampal formation, and entorhinal cortex
basal temporal cortex extending over the lateral posterior temporal cortex, parieto-occipital cortex, and posterior cingulate gyrus
frontal lobes

Anatomical Changes

Cerebral Atrophy
Neuronal Loss – prominent in the nucleus basalis, septal nuclei, and nucleus of the diagonal band where cholinergic projections arise. Also present to a lesser extent in locus ceruleus (norepinephrine) and raphe nuclei (serotonin).
Amyloid Plaques (aka senile plaques) – insoluble protein core containing beta-amyloid and apolipoprotein E (APOE) surrounded by abnormal axons and dendrites called dystrophic neuritis.
Neurofibrillary Tangles – intracellular accumulations of tau proteins – prominent in the nucleus basalis, septal nuclei, and nucleus of the diagonal band where cholinergic projections arise. Also present to a lesser extent in locus ceruleus (norepinephrine) and raphe nuclei (serotonin).

Cognitive Features

Show more problems with short term memory and explicit vs. Implicit learning
Remote memory relatively preserved, but may deteriorate in later stages
associated w/anterograde memory loss, followed by retrograde; the first area of the brain to show pathology is the medial temporal cortex. As other areas b/c involved, (lateral temporal and frontal lobes) retrograde amnesia is observed
Dominant early feature is memory loss (i.e., of recent memories or new learning). Next common feature is word-finding difficulty (i.e., anomic aphasia), along with apraxia and visuospatial deficits. Behavioral difficulties typically occur later in the disease course as compared to frontotemporal dementias, and hallucination are uncommon, especially early in the disease course unlike dementia with lewy bodies. Motor disturbances are usually not present early on; other diagnoses should be considered if motor disturbances are among the early clinical signs.

Pathological Findings

Neuritic Plaques – found chiefly in the cerebral cortex; these plaques are nonspecific –they can be found in patients with Down’s syndrome or other forms of dementia (can also be see in a diminished number in non-Alz. patients)
Paired Helical filaments/neurofibrillary tangles – found in the cortex and the hippocampus (again, these are nonspecific) – there is some debate in the literature re: whether plaques or tangles are most closely related to cognitive deterioration, however, most recent findings suggest that the amount of tangles is directly correlated w/degree of cognitive deterioration
Granulovacular Bodies – outer membranes with small dense granules in the center – more common in Alz patients than in the general aged population; degeneration of cells, occurs especially in hippocampus

Other Neuroanatomical Correlates

Neocortical changes – cortical atrophy – loses as much as 1/3 of its volume as the disease progresses. This atrophy is not uniform:
- primary sensory and motor areas are spared
- most extensive change to parietal tertiary areas, inf. temporal cortex and limbic cortex (i.e., primarily the mesial temporal, parietal, and frontal convexity regions)
- frontal lobes also affected but less than those listed above
- Limbic cortex changes – the most severe degenerative changes. The Entorhinal cortex shows the most cell loss; responsible for relaying information to and from the neocortex and hippocampus. So, damage here is equivalent to loss of the hippocampal formation.
- Cell changes – there is a dispute as to whether cell are actually lost or whether they simply shrink. The more widespread cause of cortical atrophy appears to be the loss of dendritic arborization. It should be pointed out that elderly w/o Alz. appear to increase their arborization, so this sign is not merely a development associated with aging.
- Neurotransmitter Changes – although many studies emphasize the reduction of Ach in Alz. patients, it should be noted that in fact there are marked reductions in many transmitter systems and the patterns of loss are uneven from patient to patient. But strongest association between dementia and cell degeneration occurs with dysfunction in cholinergic neurons (hence newest interventions which focus on enhancing cholinergic function such as Tacrine)

Genetics

Chromosome 19 – associated with late-onset AD (after age 60) – encodes APOE and has several different alleles. Presence of the E2 allele reduces the risk of developing AD, while presence of the E4 allele increases the risk (risk is increased the most with presence of E4 allele and history of head injury with LOC) – thought to play a role in modulating plaque formation and clearance
Chromosome 12 – associated with late-onset AD – encodes alpha2-macroglobulin (a protein). Two alleles have been identified that increase susceptibility – thought to play a role in amyloid deposition.
Chromosome 21 – associated with early-onset AD (as early as the 3rd and 4th decade) – mutations of the amyloid precursor protein – connection with Down’s syndrome (extra chromosome 21) whose victims develop early pathologic and clinical features of AD after age 30.
Chromosome 1 – also associated with early-onset AD – mutations of the presenilin 1 and presenilin 2 genes.

3 STAGES

Tend to occur in an orderly and consistent manner

Stage 1 (first 1-3 years)
- Memory – new learning defective, mildly impaired remote memory
- Visuospatial skills – topographic disorientation, poor complex construction
- Language – empty speech with few substantive words and paucity of ideas, anomia
- Personality – indifference, occasional irritability
- Motor systems – normal, including speech articulation
- EEG – normal
- MRI/CT – normal

Stage 2 (2-10 years)
- Memory – recent and remote recall more severely impaired
- Visuospatial skills – poor constructions, spatial disorientation; patients cannot find way about or copy constructions
- Language – fluent aphasia, impaired comprehension, but relatively preserved repetition
- Cognitive skills – severely impaired
- Calculation – acalculia
- Praxis – ideomotor apraxia
- Personality – indifference or irritability
- Motor system – restlessness, pacing
- EEG – slowing of background rhythm
- CT/MRI – normal or ventricular dilation and sulcal enlargement
- PET/SPECT – bilateral parietal and frontal hypometabolism/hypoperfusion

Stage 3 (8-12 years)
- Intellectual functions – severely impaired
- Language – verbal output is reduced to echolalia, palilalia or mutism
- Motor – limbs assume a rigid and flexed position
- Sphincter control – urinary and fecal incontinence
- CT scan – diffuse cerebral atrophy w/ventricular dilation and sulcal enlargement
- PET/SPECT – bilateral parietal and frontal hypometabolism/hypoperfusion
- EEG – diffusely slow
- death often results from pneumonia or urinary tract infection w/sepsis

Possible Causes

Genetics – possible cause; there is an increased frequency in families who have a member with Alz., and a higher risk if family members have Down’s syndrome (perhaps caused by a gene/group of genes)
Trace Metals – early studies w/ animals have shown neurofibrillary degeneration similar to what is seen in Alz. when they were given aluminum salts. Also, Alz. patients have an increase of 10 – 30 times the normal concentration of aluminum in their brains. But, earlier studies of link to aluminum have not been confirmed
Immune Reactions – some believe that in old age the immune system loses its ability to recognize it’s own body and, therefore, develops antibodies w/c attack the brain and cause neuronal degeneration
Slow Viruses – some believe that it is caused by a virus w/ takes years to develop. (Creutzfeldt-Jakob’s disease appears to be caused by slow viruses w/c can be passed onto other humans and animals). Attempts to localize viruses have been unsuccessful.

Pick’s Disease

Rare disorder consisting of atrophy of frontal and temporal lobes from unknown causes

like DAT, it is also a cortical dementia

Symptoms

characterized by symptoms that are virtually indistinguishable clinically from Alz., but at autopsy the disease can be distinguished, b/c atrophy is confined to the frontal and temporal cortex, and the plaques and tangles characteristic of Alz. are not present

Differences between Pick’s and Alzheimer’s Disease

less memory, calculation and visuospatial impairments but
more extravagant personality alterations
both diseases produce aphasia
- but Pick’s have a greater tendency to produce a stereotyped verbal output, repeating the same story or joke again and again
Kluver-Bucy symptoms; hyper oral tendencies are characteristic
Pick’s patients are also likely to demonstrate changes in personality and social conduct (consistent with frontal lobe deficits)
Normal EEG late in course of illness can also help to differentiate from Alz
pathologically- focal atrophy in the frontal and/or anterior temporal lobes
histologically – inflated neurons and neurons containing highly argyrophilic Pick bodies
neuronal loss and a fibrillary gliosis of the subcortical white matter
EEG – normal
On autopsy – neurofibrillary tangles and senile plaques are absent
NO selective involvement of a selective transmitter has been found

Diffuse Lewy Body Dementia

There is some controversy regarding how this dementia may be distinguished from Pick’s and/or Alzheimer’s dementias….

Characterized by

Fluctuating arousal throughout the day which leads to differences in overall cognitive functioning
Visual hallucination
Labile affect
Parkinsonian symptoms but symptoms of dementia more similar to DAT
These patients are NOT responsive to l-dopa, and are overly responsive to DA blocking agents
Early age of onset
Lewy bodies are found in the cortex rather than confined to the basal ganglia as they are in Parkinson’s patients

Creutzfeldt-Jacob’s Disease

caused by a rapidly progressive viral infection of the nervous system w/c usually leads to death w/in 6 months of onset

the virus is an unconventional slow virus w/c differs from conventional viral agents in its failure to stimulate an inflammatory or immune response, its invisibility to electron microscopes and its unusual resistance to traditional physical and chemical disinfection
has been related to sporadic, familial and transmitted causes
leads to generalized cortical atrophy
symptoms may affect fxn of the spinal cord, cerebellum, extrapyramidal system or cortex
as the disease progresses, the virus spreads to involve the nervous system diffusely and the patients eventually die in a vegetative state
myoclonus is a prominent clinical finding but may not appear until late in the course of the disease

Difference between Alzheimer’s and Pick’s

Course is very rapid, leading in just a few months to stupor, coma and death.
memory loss is prominent from the outset, but deterioration can be measured nearly day to day
at autopsy there is a generalized thinning of the cortex and generalized abnormalities in subcortical structures
may affect spinal cord, cerebellum, extrapyramidal system or cortex
rare disorder – occurs in 1/1,000,000
clinical triad – dementia, involuntary movements (especially myoclonus) and periodic EEG

bovine spongioform encephalopathy

considered a new variant of CJD – associated with mad cow disease and has an earlier age of onset

Other Prion Related Dementias

kuru
fatal familial insomnia
bovine spongioform encephalopathy

Other Dementias of the Frontal Lobes

Progressive subcortical gliosis – extensive frontotemporal atrophy (like Pick’s) but no Pick’s cells
Long duration of Creutzfeldt Jacob Disease
On autopsy 10-15% of suspected Alz. Patients end up having another variant of a degenerative dementia with frontal and anterior temporal lobe pathology

Definition of frontal lobe dementia

A degenerative condition characterized by changes in personality, breakdown in social conduct, loss of social awareness and emotional empathy, disinhibition (the major finding), impulsivity, unconcern, changes in eating conduct (hyperphagia) and stereotyped and perseverative behavior.

EXTRAPYRAMIDAL SYNDROMES W/DEMENTIA

e.g.’s Huntington’s, Parkinson’s, Wilson’s disease and progressive supranuclear palsy

Dementia is present in ~ 60% of patients w/ Parkinson’s disease (and approximately 93% have some deficits on npsych testing
Pathologically Parkinson’s disease is characterized by loss of dopamine-containing cells in the substantia nigra

Huntington’s disease

dementia is a uniform part of the disease and may be the initial symptoms preceding the appearance of chorea or other abnormalities

pathologically – cellular loss in the caudate and putamen and some atrophy of the thalamus

Huntington’s Chorea

A degenerative loss of neurons in basal ganglia, frontal cortex and corpus callosum due to a genetic abnormality ~ leads to progressive intellectual deterioration and abnormal movements

autosomal dominant (chromosome 4); rare degenerative disorder – approximately 5/100,000
associated with repeats of the trinucleotide CAG (the more repeats you have, the more severe the disorder)
usually diagnosed in late 30’s or 40’s although has been seen as young as 4 years
patients known to have Huntington’s disease are impaired at a broad range of memory, perceptual, and various frontal lobes tests
presentation can be quite variable – with cognitive or affective symptoms seen first; however, patients with early onset (e.g., childhood) frequently demonstrate parkinsonian symptoms rather than chorea first
people in the at-risk groups appear to perform poorly only on the frontal lobe tests, suggesting that these tests may be useful as predictors

Symptoms

dementia (concentration/attention; executive abilities; memory – storage and retrieval)
- has both cortical and subcortical features, but disorders which do not occur include apraxia, aphasias and agnosias (w/c do result from progressive cortical disorders)
choreiform movements – frequent, discrete, brisk movements; jerks of pelvis, trunk, limbs, accompanied by dystonic posturing of the extremities and trunk; face has intermittent frowns, grimaces and smirks
- first symptom – usually a reduction of activity and restriction of interest
- first movements usually appear w/in a year after onset of psychiatric symptoms. The involuntary movements are initially slight and consist of little more than continuos fidgeting — but increase until incessant
- the movements never involve single muscles but include whole limbs or parts of a limb
- they are also irregular and follow no sense of pattern
- eventually the movements b/c controllable and affect the head, face, trunk, and limbs – impeding all voluntary movements including speech and swallowing
slow voluntary movements
impaired saccades
gait abnormality
psychiatric disturbances (in ~ 50%)
subtle alterations in personality, memory & motor coordination often the first symptoms
oculomotor disturbance
small percentage have parkinsonian features
language affected later in disease, but hard to test b/c of dysarthria in later stages
in absence of positive family history it is important to rule out Wilson’s disease

Anatomy

at autopsy brains are shown to show shrinkage and thinning of the cerebral cortex and the basal ganglia (in particular, the caudate) is grossly atrophied
MRI and CT scan often show caudate atrophy, especially in later stages – atrophy of the caudate frequently correlates with severity of the dementia
theory – neurotransmitters w/c normally inhibit the DA pathways (GABA and NE) die during the course of the disease creating a hyperactive DA system – w/c leads to the chorea

Parkinson’s Disease

due to the degeneration of the substantia nigra and to the loss DA w/c is produced by this nucleus; the substantia nigra is the source of DA for the basal ganglia (Parkinson’s patients show a decrease of brain DA of over 90%)

although it is a subcortical dementia, can see some cortical changes…

Most common extrapyramidal disorder – affects 1/100 over age 65
Does not appear to be inherited
Environmental toxins may play a role

Features

Clinically diagnosable dementia occurs in approximately 20-60%
Bradyphrenia or mental slowing may occur early and in a large percent of clients
Memory problems
Executive problems
Attentional difficulties
Visuospatial deficits
No cortical disturbances like aphasia or apraxia (later stages may show naming problems
Depression relatively common (~30%)
Disorders of movement (see below)

4 Major Symptoms

(resting tremor*, cogwheel rigidity*, bradykinesia*, and disturbances of posture) each of these symptoms can affect different body parts in different combinations.

“classic triad of symptoms” can be divided into:
- positive symptoms – actions w/c are not seen in normals
- negative symptoms – inability to engage in behaviors that normals can

Positive Symptoms include

Tremor at rest – stop during voluntary movements or during sleep; tremors often have a “pill rolling” quality. Are frequently asymmetrical!!
Muscular rigidity – increased muscle tone simultaneously in both extensors and flexors – muscles allow movement for a short distance and then resist movement again (cogwheel effect)
Involuntary movements – may include continual changes in posture, sometimes to relieve tremor or stiffness, but often for no apparent reason – sometimes referred to as akathesia

Negative Symptoms Include

Disorders of posture – inability to maintain or difficulty in maintaining a part of the body in normal position (e.g., head may droop)
Disorders of righting – difficulty in standing from a sitting position
Disorders of locomotion – difficulty initiating stepping and when they do they shuffle; often once they begin to walk they take faster and faster steps and end up running (festinating gait)
Disturbances of Speech – difficulties in the physical production of sound
Akinesia – poverty or slowness of movement; may manifest itself in blankness of facial expression, lack of blinking, etc.
Aphagia – difficulty in chewing and swallowing

Anatomy and Treatment

Neuronal loss in substantia nigra, associated with Lewy bodies leading to decrease in striatal dopamine concentration
Neurochemical deficiencies: dopamine (especially), acetylcholine, serotonin and corticotrophin releasing features
Medications can help with motor symptoms, but do not improve cognitive deficits – in fact, in some patients medications can cause confusion
Similarly, neurosurgery will selectively help only one major physical symptom –
- Pallidotomy can help treat the dyskinesia
- Thallotomy helps with the tremor (“t” helps with “t”)

Other Extrapyramidal Dementias

(i.e., “Parkinson +” or “Multisystem” dementias)

Progressive supranuclear palsy (PSP)

in addition to parkinsonism symptoms, causes swallowing difficulties and supranuclear opthalmoplegia
Also known as Steele-Richardson-Olszewski syndrome
Due to degeneration of multiple structures including the superior colliculus, red nucleus, dentate nucleus, subthalamic nucleus and globus pallidus
Gaze paresis – loss of downward gaze, leads to frequent falls and ‘dirty tie’ sign
Axial rigidity – trunk/neck rigidity producing erect or hypererect rather than stooped posture
Bradykinesia
Pseudobulbar palsy – masked face, increased jaw and facial jerks, exaggerated palatal and pharyngeal reflexes, dysphagia, drooling, emotional lability
Gait disorder, falls and akinesia can also be present
“wide-eyed stare”

Wilson’s disease

Characterized by hepatic and CNS dysfunction due to abnormalities in copper metabolism; peak onset teens-20’s

Neurologic symptoms include Parkinsonian symptoms such as tremor, rigidity, dysarthria, and akinesia, as well as dystonia, “wingbeating tremor,” and ataxia
Psychosis, mood changes and dementia can also occur
Treatable if diagnosed early
Autosomal recessive disorder (chromosome 13)
Kaiser Fleischer rings are present in most cases – while it is pathognomonic it may not be seen in every patient

Hallerverorden-Spatz disease

Rare inherited and progressive illness with late childhood or early adolescent onset, characterized by dementia with spasticity and rigidity, dystonia or chorea. Caused by an accumulation of iron in the brain. There is no current cure.

Syndenham’s Chorea

Affects children between the ages of 5 and 15

Associated with rheumatic fever and Pandas
Also frequently associated with tics, tourette’s, ADHD and dystonia

Subacute Sclerosing Panencephalitis (SSPE)

Develops primarily in children
Poor school work, behavioral disturbance, restlessness, personality change —- dementia
Myoclonus is a characteristic symptom
Rarely develops in adults
Measles may be a cause

Shy Drager Syndrome

Parkinson’s symptoms + autonomic disturbance (impotence, urinary incontinence)

Olivopontocerebellar atrophy

Parkinson’s symptoms + ataxia – but NO rigidity or bradykinesia (DOES have tremor)

Striato-Nigral Degeneration

Patients become stiff and slow develop difficulty with walking and balance
Usually do not have a tremor, but cannot be distinguished from PD patients by a neurological exam alone
Do not respond to L-dopa
Can be distinguished from PD on autopsy because most of the damage is in the striatum rather than the substantia nigra

MULTI-INFARCT DEMENTIA

specific characteristics are variable, but includes psychomotor retardation and emotional lability in most cases

Second most common form of dementia following Alzheimer’s

History

abrupt onset
stepwise deterioration/fluctuating course
previous stroke or transient ischemic attacks
previous hypertension or other cardiovascular disease

Neurological Examination

focal deficits
pseudobulbar palsy (w/ dysarthria)
gait disturbance
psychomotor retardation

Mental Status Exam

dementia (cortical and/or subcortical features)
depression
emotional lability
relative preservation of personality

Laboratory assessment

focal slowing on EEG
infarcts usually visible on CT (but normal scan does not preclude the diagnosis )

Treatment

discovery and treatment of underlying risk factors (e.g., emboli, hypertension, smoking, diabetes)
Dysarthria and aphasia may improve w/ speech and language therapy

Risk Factors

Hypertension, abnormal lipid levels, smoking, diabetes, and obesity
Patients with cerebrovascular disease may have vascular disease AND episodes of coronary insufficiency with associated systemic hypotension leading to more diffuse brain damage

Key factors to differentiate from Alzheimer’s Dementia

Abrupt onset
Stepwise deterioration
Focal neurological symptoms
Risk factors for vascular disease
Tend to have an earlier onset that DAT and are more common in men

Lacunar Strokes – see vascular notes Binswanger’s disease – when strokes are limited to white matter double check – notes have it both for gray and for white matter…

Other Causes of Dementia

Vasculitis Dementia

Caused by inflammation of the cranial arteries
Often associated with systemic illnesses such as giant cell arteritis and lupus

Bacterial Infections Producing Dementia

syphillic general paresis

Probably the best known example. It is currently rare;

typically appears 15 – 30 years after the initial infection and is characterized by progressive intellectual impairment combined in some cases w/ psychosis
manifests as multiple strokes and associated dementia
also accompanied by changes in personality
examination of CSF can lead to definitive dx

Lyme disease

symptoms include facial palsy, headaches, peripheral neuropathy, meningitis, memory difficulties, irritability, depressed mood

African trypanosomiasis

African sleeping sickness transmitted by the tsetse fly

Viral Infections Producing Dementia

Dementia can be caused by acute encephalitis or by affects of neurotransmitter dysfunction, demyelination, etc.

Postinfection encephalomyelitis

May be caused by measles, varicella, rubella and other viral illnesses

HIV Type 1 encephalopathy

(see it’s own section below)

Progressive multifocal leukoencephalopthy

due to an opportunistic infection that occurs in immunologically compromised individuals

Cruetfeldt-Jakob disease

– see own section

Dementia due to HIV Disease

Primarily subcortical dementia but with some cortical changes

diffuse, multifocal destruction of white matter and subcortical structures
characterized by forgetfulness, slowness, poor concentration, and problem solving difficulties
behavioral manifestations include: apathy, social withdrawal
may have visual hallucinations, delusions or delirium
tremors, impaired repetitive movement, imbalance, ataxia, hypertonia
FL signs
Affects 20-60% or AIDS patients and over 90% of patients dying with AIDS show evidence of subacute encephalitis
Micronodules are scattered throughout brain

Chronic Meningitis

may lead to dementia and can be caused by syphilis, tuberculosis, fungi or parasites.
In addition to intellectual deterioration, affected patients manifest cranial nerve palsies, stiff neck and headache
focal neurological deficits may occur and hydrocephalus may be an acute or late complication

Toxic and Metabolic Dementias

Toxic and metabolic disturbances frequently produce intellectual disturbances

when the mental state disturbance has an abrupt onset and a short course, an acute confusional state is diagnosed
if there is a gradual onset and is insidiously progressive, persisting for weeks, months or longer, the disorder is a dementia syndrome
adult onset biochemical disorders
- although rare, adult onset forms of inherited metabolic dementias can occur
characterized into leukoencephalopathies, encephalopathies, etc.
metabolic disorders – can include hypoxia due to cardiopulmonary disease or failure, anemia, etc. and endocrine disease
- most prevalent in elderly populations
- caused by diffuse dysfunction of the brain at the molecular-chemical level
- some can be reversible
- can be caused by neuroleptics, antidepressants, metals, nutritional deficiencies, or over the counter medications

Endocrine Dysfunction

can cause cognitive impairments
treatable with hormone replacement
hyperthyroidism – anxious, restless, tachycardia, palpitations, heat intolerance
hypothyroidism – leads to basal ganglia calcifications…..Parkisonism-like or chorea-like symptoms

Non-Degenerative Dementias

may be due to vascular, viral, or bacterial causes

Dementia Pugilistica

syndrome usually begins with a gait disturbance and slurring dysarthria
gradually progresses into an extrapyramidal Parkinsonlike syndrome with evidence of both pyramidal and cerebellar dysfunction
seizures may occur in some patients
dementia appears later in course, first manifestation is usually disturbance in memory
psychomotor retardation is apparent
may be personality changes and general intellectual decline
psychiatric manifestations include: paranoia, euphoria and depression
CT may demonstrate cerebral atrophy w/ventricular enlargement
Autopsy may also demonstrate thinning of the corpus callosum, depigmentation of the substantia nigra and presence of neurofibrillary tangles

Hepatic dysfunction

Can be associated with mental impairment, probably due to elevated levels of ammonium
~ 5% of patients with cirrhosis may develop encephalopathy
with every episode of liver failure, a static dementia syndrome may result
motor symptoms are frequently associated with the dementia

Other….

Normal pressure hydrocephalus – characterized by dementia, gait disturbance and urinary incontinence, but the clinical presentation is nonspecific (this is discussed in more detail in another section of your study notes)
Head trauma
Neoplasms
Cardiopulmonary dysfunction – multiple episodes of hypoxia may lead to step-wise deterioration

Characteristics of the 3 Stages of DAT and Pick’s Diseases

Stage DAT Pick’s Stage 1

Language Anomia, empty speech Anomia

Memory Defective Relatively spared

Visuospatial Skills Impaired Relatively spared

Calculation Impaired Relatively spared

Personality Indifferent Disinhibited

Motor System Normal Normal

EEG Normal Normal

CT scan Normal Normal

Stage 2

Language Fluent aphasia Aphasia, stereotyped output

Memory Severely impaired Impaired

Visuospatial ability Severely impaired Impaired

Personality Indifferent Disinhibited

Motor system Restlessness Restless stereotyped behavior

CT scan Atrophy frontal &/or temporal atrophy

Stage 3

Intellectual fxn Severely impaired Severely impaired

Language Palilailia echolalia or mutism Echolalia, mutism

Sphincter control Incontinence Incontinence

EEG Diffuse slowing Diffuse fronto- temporal slowing

CT scan Diffuse atrophy same as stage 2

CORTICAL vs. SUBCORTICAL DEMENTIA

subcortical dementia – dementias produced by diseases affecting subcortical structures; cardinal features include psychomotor retardation, poor fluid thinking, memory impairment (difficulty retrieving spontaneously, aided by cues and structure), abnormal cognition, mood disturbances and speech or motor system abnormalities
- e.g.’s Parkinson’s disease, Huntington’s disease, Wilson’s disease, Progressive Supranuclear Palsy
- motor impairments include: stooped/hyperextended posture, slow movements, choreotathetosis, tremor, dystonia, and dysarthria
- causes – extrapyramidal disorders, hydrocephalus, white matter disease, and subcortical vascular disease that affects basal ganglia, thalamus and brainstem
cortical dementia (DAT and Pick’s) – common features include: aphasia, agnosia, apraxia, amnesia, visual-spatial deficits, persevered personality, deficits in judgement, BUT neurological exam is relatively normal as are motor fxn, gait, posture, and tones; speech also has normal volume and articulation
multi-infarct dementia, viral infections, trauma and chronic-toxic metabolic disorders can produce symptoms of both kinds of dementia

Comparison Table

Clinical Characteristics	Cortical Dementia	Subcortical Dementia
Language	Aphasia early	No aphasia (but anomia and comprehension deficit when severe)
Memory	Recall & Recognition Impaired	Recall impaired; recognition normal or better preserved than recall
Visuospatial Skills	Impaired	Impaired
Calculation	Involved early	Preserved until late
Other Intellectual fxns	Acalculia, Apraxia,Agnosia	Poor strategy formulation

Frontal systems	Impaired to a degree consistent with other impairments	Disproportionately affected
Speed of cognition	Normal until late in course	Slowed early
Personality	Unconcerned	Apathetic
Speech	Normal articulation until late	Dysarthric
Posture	Upright	Bowed or extended
Coordination	Normal until late	Impaired
Motor Speed	Normal	Slowed
Motor system	Relatively spared until late	Abnormal (Parkinsonism, chorea,Dystonia, etc.)
Anatomic Involvement	Neocortical association areas and hippocampus	Thalamus, basal ganglia,and brainstem

Classification of Major Causes of Dementias

Cortical Dementias	Combined cortical & subcortical dementias
Alzheimer’s	Multi-infarct dementias
Frontal Lobe Degeneration	Infectious dementias
Subcortical Dementias	Toxic and metabolic encephalopathies
*Extrapyramidal Syndromes*	Endocrine disorders
Parkinson’s disease	Nutritional deficiency states
Huntington’s disease	Drug intoxications
Progressive supranuclear palsy	Miscellaneous dementia syndromes
Wilson’s disease	* posttraumatic
Spinocerebellar degenerations	* postanoxic
Idiopathic basal ganglia calcifications	* neoplasms
Hydrocephalus	xxx
Dementia syndrome of depression	Differentiate from:
White matter disease	* Delirium
* MS	* Depression
* HIV encephalopathy	* Normal Aging
Vascular dementias