Confusion/Memory Loss

Alzheimer’s Disease

• Path:
  • 1. extracellular senile plaques (neuritic plaques = Aβ protein) in the grey matter of the brain
    • process of neuritic plaque formation: β-secretase and γ-secretase cleave transmembranous APP -> Aβ peptide aggregation -> formation of insoluble plaques with tau protein and microglial -> neurotoxic effect
  • 2. intracellular neurofibromas tangles
    
    • composed of hyperphosphorylated tau protein (a microtubule-associated protein)
    • process of neurofibrillary tangle formation: hyperphosphorylation of tau protein -> formation of intracellular fibrils -> neurotoxic effect
  • 3. overall reduction of cholinergic function
  • 4. Cerebral Atrophy
    • 1. damage to the hippocampus and parahippocampal cortex
      
    • 2. degeneration of cholinergic neurons in the nucleus básalos of Meynert
      
    • 3. diffuse cortical atrophy occurs as the disease progresses

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  Presentation:
  • – Most common cause of dementia
    
  • – Insidious onset with steady, progressive decline in cognitive function over years
    
  • – Earliest findings are impairment in memory and visio-spatial abilities
    
  • – Clinical Diagnosis
    • 1. cognitive Impairment
      
      • MC sxs:
        • 1. short-term memory impairment
          
          • 1. insidious onset
            
          • 2. slow progress
            
          • 3. episodic memory affected first
        • 2. language impairment
          
        • 3. temporal and spatial disorientation
          
        • 4. impairment of executive functions and judgment
      • Less Common sxs:
        • 1. primary progressive aphasia
          
        • 2. apraxia
          
        • 3. alexia
          
        • 4. agnosia
          
        • 5. acalculia
    • 2. non-cognitive Impairment
      • 1. behavioral changes
        
      • 2. mood disorders e.g., depression
        
      • 3. anxiety and mutism
        
      • 4. hallucinations and paranoia
        
      • 5. hyposmia
        
      • 6. insomnia
        
      • 7. urinary incontinence
        
      • 8. myoclonus
        
      • 9. seizures

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  Risk Factors:
  • 1. genetic factors
    
  • 2. age
    
  • 3. family history
    
  • 4. diabetes, obesity, dyslipidemia
    
  • 5. HTN, peripheral atherosclerosis, CVS disease
    
  • 6. lack of physical activity
    
  • 7. traumatic brain injuries
    
  • 8. sleep deprivation
    
  • 9. environmental factors

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  Work up:
  • CSF:
    • 1. increased phospho-tau protein
      
    • 2. decreased β-amyloid proteins Aβ1-42
  • CT/MRI:
    • 1. generalized/focal cerebral atrophy (e..g, ventriculomegaly, narrowing of gyri, hydrocephalus ex vacuo)
      
    • 2. disproportionate atrophy of the hippocampus and/or medial temporal lobe
    • bilateral brain atrophy with prominent cerebral sulci and an enlarged subarachnoidal space (green overlay); the bilateral, sharply demarcated, hyperintense, circular areas in the white matter (circled in white) are enlarged perivascular spaces – Virchow-Robin spaces
  • EEG:
    • 1. slower basic rhythm
      
    • 2. evoked potentials: long latency
  • PET scan:
    • 1. FDG-PET: temporoparietal hypometabolism
      
    • 2. amyloid PET: increased amyloid uptake signal
  • Earliest Gross Path:
    • damage to the hippocampus and parahippocampal cortex (medial temporal lobe structures) -> atonal degeneration and neuronal loss

Creutzfeldt-Jakob Disease (CJD)

– Dementia, mood, anxiety, movement disorders
– Rapidly progressive dementia; usually sporadic but can be rarely familial. Occurs in 7th decade, fatal in 7 months.
– Caused by prions (small proteinaceous particle’s that cause spongiform changes in the brain)

Delirium

1. Disturbance of CONSCIOUSNESS (can’t focus or shift attention)
2. Change in COGNITION (memory, language)
3. Develops over SHORT period of time and FLUCTUATES
4. Caused by a general MEDICAL condition

Depression with Pseudodementia

– Patient often tends to emphasize disability related to memory loss much more than patients experiencing true dementia
– Appears to have dementia
– Unable to remember correctly,
– Cannot calculate well
– Complains, bitterly, of lost cognitive abilities or skills
– High risk of progressing to dementia
– Depression or mild depressive symptoms can be comorbid

Clues:
– Recent weight loss
– Worsening sleep
– Frequent crying spells
– Self-deprecating comments,
– Recent-onset behavior changes (social withdrawal, psychomotor agitation, extreme negativism)

Hypoglycemia

Hypoglycemia Mnemonic
T – Tachycardia
I – Irritability
R – Restless
E – Excessive Hunger
D – Diaphoresis/Depression

Hypoglycemia Symptoms
– Autonomic: Anxiety, Palpitations, Sweating, Tingling, Trembling
– Neuroglycopenia: Irritability, drowsiness, dizziness, blurred vision, difficulty with speech, confusion, feeling faint

Normal Pressure Hydrocephalus (NPH)

– Adams/Hakim Triad (“wet, wobbly and wacky”):
1. Wet = Incontinence
2. Wobbly = Gait ataxia (Wide-based)
3. Wacky = Dementia

Vascular (multi-infarct) dementia

– Often coexists with Alzheimer’s Disease
– Look at history of atherosclerotic vascular disease (i.e. stroke, MI)
– Classically more step-wise deterioration in vascular dementia compared to steady cognitive decline seen in Alzheimer
– May be earlier loss of executive function and personality changes in vascular dementia