Dementia – Impairment in memory

• Cortical Dementia – primary destruction of cortex. Prototype: Alzheimer’s (focal cortical signs,otherwise normal neuro exam)
• Subcortical Dementia – Secondary destruction of cortex. Prototype: vascular dementia (stroke) which has multiple cortical signs with an abnormal neuro exam.

Alzheimer's Disease – most common cause of dementia, most prevalent CNS degenerative disease

• Pathology: Senile plaques and Neurofibrillary tangles (NFTs). Clinical symptoms are more closely related to distribution of NFTs which extend through: Mesial temporal lobe, Dorsolateral parietal cortex, to ventral frontal lobe (associated with limbic system). These normally regulate behavior and emotion and are prominently affected by AD.
• Dementia of the alzheimer’s type: progressive memory impairment of short term memory at first, progressing to loss of long term memory in later stages (primary feature!!). May involve facial recognition areas of cortex
• 1 or more of the following:
• aphasia (no fluency/can’t find words)
• apraxia
• agnosia
• executive dysfunction (inability to suppress inappropriate responses to envt: socially inappropriate behavior, disinhibition, poor task persistence)
• complex visual function deficit ("Sundowning"=ß visual inputÞ can’t see well at night);gradual onset, continuing decline
• Other Areas Affected: comprehension(Wernicke), repetition(arcuate fasciculus-connects Wernicke to Broca), fluency(Broca)
• Correlates of Neurotransmitter loss in AD – ß Ach, ß NE, ß serotonin, ß Dopa
• (1) Acetylcholine – ACh is important in attention and memory. ACh is produced in deep forebrain nuclei (Nucleus basalis, Broca) and is sent out to rest of cortex via axons (especially to frontal lobes and hippocampal region which is important in memory acquisition). These nuclei get destroyed in AD. Inhibition of ACh breakdown has been shown to Ý cognition, promote maintained function in daily life, and delay nursing home placement.
• (2) Monoamines – Norepinephrine (NE) and Serotonin (5HT) play a role in mood, affect, anxiety, and motivation. Both the Locus Ceruleus (NE) and Raphe Nulcei (5HT) are destroyed in AD Þ depression and apathy in AD patients Most modern antidepressants primarily affect serotonin.
• (3) Dopamine – Dopamine also contributes to motivation. Made in brainstem and regulates frontal lobe. Loss of dopamine-producing neuronsÞ psychosis(25-50% of patients) and Parkinson’s (30% of patients). Most antipsychotics affect dopamine.

• Dementia with Lewy Bodies (DLB): Lewy bodies (intracytoplasmic inclusion), 2^nd most common dementing disease in US (not vascular dementia as previously thought)
• Features: fluctuating alertness and attention, visual hallucinations, parkinsonism (tremor is NOT prominent)
• Supportive features: repeated falls, syncope, episodic unawareness, neuroleptic sensitivity, systematized delusions or hallucinations
• Clincal syndrome: typical onset within 1 year of parkinsomism, executive function disorders, posterior cortical findings: apraxia, visuospatial disorders. AD pathological features are present in a majority of DLB cases.
• Dementia of Frontal Type (Pick’s disease) – Pick body, neuronal loss follows different distribution than AD!
• Frontal lobe is important for regulation of behavior.
• Lesions of: Mesial surface: apathy, aspontaneity; Dorsolateral surface: envt dependence, preservation, motor impersistence; Orbital surface: disinhibition, social impropriety
• Two major syndromes:
• (1) loss of judgment and disinhibition or social misconduct or withdrawal/apathy
• (2) loss of language, ie expression or comprehension or both
• Behavior in frontal dementia: disinhibition and impuslivity, ß personal and social awareness, distractibility and impersistence. (ex: older patient who makes sexual propositions to women in church around his wife)
• Ischemic Vascular Dementia (accociated with strokes)-criteria: cognitive impairments accociated with cerebrovascular disease evident by history, exam, and brain imaging. Also evidence that cognitive impairment and cerebrovascular disease related! (abrupt/stepwise/fluctuating course, imaging findings indicating damage to regions important for cognition, etc).
• Normal Pressure Hydrocephalus – Rare, reversible form of dementia. Clinical Triad: prominent gait disturbance, moderate mental impairment, urinary incontinence. CT features: rounded ventricular frontal horns, moderate to severe ventriculomegaly, no cortical atrophy, no severe white matter disease. Drainage of CSF will likely improve gait.
• Prion disease – Creutzfeldt-Jakob Disease is a rare, rapidly progressive dementia. Clinical: onset usualy age 50-70, rapid courseÞ death in 1-2 years, behavior and cognitive changes: irritability, somatic complaints, complex visual dysfunction. General neurological features: myoclonus (often late), parkinsonism.
• Others: dementia due to: HIV, head trauma, Parkinson’s disease, Huntington’s disease