This document provides information on dementia, including its causes, symptoms, diagnosis, and treatment. The most common causes of dementia are Alzheimer's disease, vascular dementia, alcoholism, Parkinson's disease, and drug intoxication. Diagnosing dementia involves evaluating memory and cognitive function, determining if the impairment is severe enough to interfere with daily life, and ruling out treatable causes through exams, labs, and imaging. Alzheimer's disease is the most common cause and is characterized by progressive memory loss, cognitive decline, and brain atrophy and plaques seen on pathology. Treatment involves cholinesterase inhibitors or memantine to address symptoms as well as management of behavioral issues.

1. Dementia
 Syndrome characterized by deterioration of
◦ Memory + 2 other cognitive domains:
 Language
 Visuospatial ability
 Calculation
 Judgment
 Problem solving
 Praxis
 Deterioration must be severe enough to interfere with usual social
functioning and activities of daily life
Etiology of Dementia
 Most Common Causes:
◦ Alzheimer's disease
◦ Vascular dementia
 Multi-infarct
 Diffuse white matter disease (Binswanger's)
◦ Alcoholism
◦ Parkinson's disease
◦ Drug/medication intoxication
 Other Causes:
◦ Vitamin deficiencies
 Thiamine (B1): Wernicke's encephalopathy
 B12 (pernicious anemia)
 Nicotinic acid (pellagra)
◦ Endocrine and other organ failure
 Hypothyroidism
 Adrenal insufficiency and Cushing's syndrome
 Hypo- and hyperparathyroidism
 Renal failure
 Liver failure
 Pulmonary failure
◦ Chronic infections
 HIV
 Neurosyphilis
 Papovavirus (progressive multifocal
leukoencephalopathy)
 Prion (Creutzfeldt-Jakob and Gerstmann-Sträussler-
Scheinker diseases)
 Tuberculosis, fungal, and protozoal
 Whipple's disease
◦ Head trauma and diffuse brain damage
 Dementia pugilistica
 Chronic subdural hematoma
 Postanoxia Postencephalitis
 Normal-pressure hydrocephalus
◦ Neoplastic
 Primary brain tumor
 Metastatic brain tumor
 Paraneoplastic limbic encephalitis
◦ Toxic disorders
 Drug, medication, and narcotic poisoning
 Heavy metal intoxication
 Dialysis dementia (aluminum)
 Organic toxins
◦ Psychiatric
 Depression (pseudodementia)
 Schizophrenia
 Conversion reaction
◦ Degenerative disorders
 Huntington's disease
 Pick's disease
 Dementia with Lewy bodies
 Progressive supranuclear palsy (Steel-Richardson
syndrome)
 Hereditary ataxias (some forms)
 Etiology of Dementia
 Motor neuron disease [amyotrophic lateral sclerosis
(ALS); some forms]
 Frontotemporal dementia
 Cortical basal degeneration
 Multiple sclerosis
 Adult Down's syndrome with Alzheimer's
 ALS–Parkinson's–Dementia complex of Guam
◦ Miscellaneous
 Sarcoidosisa Vasculitis
 CADASIL
 Acute intermittent porphyria
 Recurrent nonconvulsive seizures
◦ Additional conditions in children or adolescents
 Hallervorden-Spatz disease
 Subacute sclerosing panencephalitis
 Metabolic disorders (e.g., Wilson's and Leigh's
diseases, leukodystrophies, lipid storage diseases,
mitochondrial mutations)
 Approach to patient with dementia
Important questions to answer:
1. What is the most accurate diagnosis?
2. Is there a treatable or reversible component to the dementia?
 Differential Diagnosis:
Treatable forms of dementia
 Neurosyphilis
 Chronic meningitidis
 Normal Pressure Hydrocephalus
 Chronic Subdural Hematoma
 Nutritional deficiencies
◦ Wernicke-Korsakoff syndrome
◦ Marchiafava-Bignami disease
◦ Pellagra
◦ Vitamin B12 deficiency
 Endocrine-Metabolic Disorders
◦ Myxedema
◦ Hashimoto thyroiditis encephalopathy
◦ Cushing Disease
◦ Chronic Hepatic Encephalopathy
 Frontal and temporal lobe tumors
 Cerebral vasculitis
 Pseudodementia of depression
 History
 Onset, duration, tempo of progression of dementia
◦ Acute or subacute confusion
 Infectious, metabolic derangement
◦ Slowly progressive memory loss in an elderly px
 Alzheimer’s Disease
◦ Stepwise progression of dementia
 Multi-infarct Dementia
 Associated symptoms
◦ Early visual hallucination, parkinsonism, delirium
 Dementia with Lewy Body
◦ History of Hypertension, Atrial Fibrillation, Diabetes
 Multi-infarct Dementia
◦ Rapid progression of the dementia in association with
motor rigidity and myoclonus
 Creutzfeldt-Jakob Disease (CJD)
◦ Change in personality, disinhibition, apathy, progressive
abnormalities in speech, relative sparing of memory
 Frontotemporal Dementia
 History
 Recurrent head trauma
◦ Dementia pugilistica
◦ Chronic subdural hematoma
◦ Normal pressure hydrocephalus
 Seizures
◦ Strokes or Neoplasm
 Gait disturbance

2. ◦ Multi-infarct dementia, Parkinson’s Disease Dementia,
Normal Pressure Hydrocephalus
 Family history of dementia
◦ Huntington Disease
◦ Familial Alzheimer Disease
 Occupation
◦ Working in a battery or chemical factory
 Heavy Metal Intoxication
 Review of medications
◦ Chronic sedative or tranquilizer intoxication
 Recent death of a loved one, depressive signs
◦ Pseudodementia secondary to depression
PE and Neurologic Examination
 Corticobasal degeneration (CBD)
◦ Dystonia, alien hand, and asymmetric extrapyramidal,
pyramidal, or sensory deficits or myoclonus
 Progressive supranuclear palsy (PSP)
◦ Unexplained falls, axial rigidity, dysphagia, and vertical gaze
deficits
 Vitamin B12 deficiency
◦ Dementia with a myelopathy and peripheral neuropathy
 Alzheimer’s Disease (AD)
◦ Earliest deficits involve verbal or visual episodic memory
 FTD
◦ Earliest deficits often involve frontal executive or language
(speech or naming) function
 DLB
◦ More severe deficits in visuospatial function but do better on
episodic memory tasks than patients with AD
 Hearing impairment and visual loss
◦ Produce confusion and disorientation mistaken for dementia
Laboratory Work-up
 Routine
◦ Thyroid Function Test
◦ Vitamin B12 determination
◦ CBC
◦ Electrolytes
◦ Cranial CT or MRI
 Optional
◦ CXR
◦ Lumbar Puncture
◦ Liver Function
◦ Renal Function
◦ Urine Toxin screen
◦ HIV, RPR, VDRL
◦ EEG
◦ Parathyroid Function
◦ Adrenal Function
◦ Angiogram
◦ Brain Biopsy
◦ PET
◦ SPECT
Alzheimer’s Disease
 Most common cause of dementia
Alzheimer’s Disease
 Prevalence
◦ Age: > 60 years
◦ Sex: slightly more in females
 Most important risk factors:
◦ Old age
◦ Positive family history of dementia
Clinical Features
 Gradual development of forgetfulness
◦ Ribot’s Law of memory
 Remote memories are preserved while recent memories
are lost
 Dysnomia
◦ Forgetting of words, especially proper names
◦ Progresses to common names à impaired speech fluency
 Tendency to repeat questions before answering à later progresses to
Echolalia
 Acalculia or dyscalculia
◦ Impaired calculation
 Visuospatial disorientation
◦ e.g. Getting lost in familiar surroundings, right to left confusion,
inability to park car, etc.
 Ideational and ideomotor apraxia
◦ e.g. Forgets how to use common objects
 Paranoia and personality changes
◦ e.g. Conviction that others are stealing from them, imprudent
financial ventures
 Unsteady gait with short steps despite intact motor strength
NINCDS-ADRDA Diagnostic Criteria for Alzheimer Disease
1. Dementia defined by clinical examination, MMSE or Blessed
Dementia Scale
2. Age of patient (> 40 years)
3. Deficits in 2 or more areas of cognition and progressive worsening
of memory and other cognitive functions (language, perception,
motor skills)
4. Absence of disturbed consciousness
5. Exclusion of other brain diseases
Pathology
 Diffuse brain atrophy
◦ < 20% of normal brain weight
◦ Usually involves the frontal, temporal and parietal lobes
 Symmetrical 3rd
and lateral ventricle enlargement
 Extreme atrophy of the hippocampus
 Widespread loss of nerve cells
Pathology
 Neurofibrillary tangles
◦ Composed of hyperphosphory-lated Tau protein
 Neuritic plaques
◦ Protein amyloid core surrounded by degenerating nerve
terminal
Pathology
 Granulovacuolar degeneration of the neuron

3. ◦ Most evident in the pyramidal layer of the hippocampus
Pathogenesis
 Tau
◦ Cytoskeletal protein for the assembly of microtubules
 In Alzheimer Disease, PSP, and Frontotemporal Dementia
◦ Hyperphosphorylation of Tau à aggregates à Neurofibrillary
tangles in the neuronal cytoplasm à Neuronal death
Pathogenesis
Pathogenesis
Pathogenesis
Pathogenesis
 Neurotransmitter abnormalities
◦ Acetylcholine
 Marked decrease in Choline acetyltransferase (ChAT) and
acetylcholine in the hippocampus and neocortex
 Probably due to loss of the cells in the Nucleus basalis of
Meynert
◦ Norepinephrine, GABA, Serotonin, Glutamate, Substance P,
Somatostatin, Cholecystokinin
 Also reduced
 Still not sure if primary or secondary to hetenogeneous
neuronal loss
Genetic aspect of Alzheimer Disease
Diagnostic Studies
 MRI or CT scan of the brain
◦ Most useful but not definitive test
◦ Show disproportionate atrophy of the hippocampi with
enlargement of the temporal horns of the lateral ventricles
◦ Most important for ruling out:
 Brain tumor
 Subdural hematoma
 Cerebral infarction
 Hydrocephalus
 Hippocampal Atrophy
 EEG
◦ Diffuse slowing (late stage)
 Neuropsychologic tests
◦ Deterioration in memory and verbal access skills
 E4 apolipoprotein allele
◦ A biomarker occasionally associated Alzheimer Disease
 Aβ to tau ratio in the CSF
◦ Not yet validated for use
 Amyloid imaging
◦ Still under study
Treatment
1. Anticholinesterases
◦ Donepezil, Rivastigmine, Galantamine
◦ Indicated for the treatment of Alzheimer Disease
2. NMDA antagonist
◦ Memantine
◦ Indicated for severe stage of Alzheimer Disease in conjunction
with anticholinesterases
3. Benzodiazepines
◦ Clonazepam, Lorazepam
◦ In severe sleep disturbances

4. 4. Antipsychotics
◦ Haloperidol, Risperidone, Quetiapine, etc.
◦ To suppress aberrant behaviors and hallucinations