Dementia

Serious loss of global cognitive ability

• Not normal age-related cognitive declines

• Impaired memory and cognitive function

• MMSE (mini mental status exam) to assess cognitive abilities

A syndrome (group of symptoms), not a specific disorder

Usually progressive- neurodegenerative

Not progressive usually if caused by… TBI or stoke, drug use

Mild Cognitive Impairment (MCI)

• MMSE score 20-26

• Cognitive deficient, but doesn’t interfere with daily living

• Sometimes a precursor to Alzheimer’s disease

Alzheimer’s Disease (AD)

• 80% of all dementias

• Slow progression

• Usually normal motor control

• Mild depression and some social withdrawal

• Early stage- lasts 2-4 years

  • Frequent memory loss of recent memories, but older memories preserved

  • Place objects in odd places

• Second stage- lasts 2-10 years

  • More pervasive memory loss, involving older memories

  • Nonsensical speech

  • Easily get lost

  • Lose inhibitions (say/ do inappropriate things)

• Late stage- lasts 1-3 years

  • Confused, unable to carry out conversations

  • Major mobility difficulties

  • Difficulty swallowing

Frontotemporal Dementia

• Most common dementia in people under 65 years old

• Executive Function

• Apathy and social withdrawal are common

• Lack of inhibition

  • Theft, erratic driving, disinhibited sexual desire

• Compulsive behaviors such as overreacting

• Loss of speech fluency, but no change in language comprehension

Vascular Dementia

• Less memory loss and more loss of cognitive speed and problem solving

• Difficulty with organization

• Difficulty deciding what to do next

• Difficulty in making a plan

• Difficulty following a series of steps (cooking)

• Showed speed of thought

• Problems concentrating

Lewy Body Dementia

• 2nd most common type of dementia

• Confusion, poor attention, visual-spatial problems, memory loss

• Fluctuating cognition

• Early Stage

  • Visual hallucinations

  • Movement disorders that look like parkinsons disease

    • Slowed movement, rigid muscles, tremor, shuffling walks

• Middle Stage

  • REM sleep disorders

• Poor regulation of blood pressure, heart rate, sweating, digestion

Chapter 4 Reading

Alzheimer’s Disease Anatomical Changes

• Shrinkage of cortex

• Shrinkage starts in cortex near hippocampus (memory) & spreads

• Ventricles (hollow pockets in brain that hold CSF) get bigger because brain is getting smaller

• Tangles of neurofibrillary tangles and amyloid plagues

  Frontotemporal Dementia

  • Shrinkage of frontal lobe not of cortex

AD: Amyloid Plaques and Neurofibrillary Tangles

Tau: Holds together microtubules

• During Alzheimers, tau becomes hyperphosphorylated in AD and doesn’t dissolve anymore, no longer binds microtubules together

• These tangles are killing neurons in AD

Tangles

• APP Amyloid precursor protein, sits in cell membranes (don’t know what they do)

Prion= Protein in cell membranes that can become misfolded, and if it interacts with a normal prion it causes them to misfold (mad cow disease)

How does AD Pathology spread across the brain?

• Starts in medial temporal lobe spread to surrounding cortex

• Beta amyloid (AB) plaque formation may spread like prions

  • Misfolded AB might serve as template for misfolding

  • AD as a communicable disease (don’t eat human brains)

Genetics of Alzheimer’s Disease

• 1% of AD cases are inherited autosomal dominant disease

• 99% show genetic predisposition

  • Heritability = 0.6 - 0.8

• APOE

  • Lipid binding protein synthesized in liver, glial cells, and neurons

  • Neurons have receptors for APOE

  • e4 allele (14% of pop) increases AD risk up to 15x

  • e2 allele (7% of pop) reduces AD risk

  • e3 allele (79% of pop) is neutral

• Many other genes that have much smaller effects

Verret el al Paper

• Parvalbumin-positive (PV) inhibitory interneurons, which are essential for regulating neural network activity and cognitive functions.

• Restoring the function of inhibitory interneurons is suggested as a possible therapeutic approach