Mixed Dementia

Vascular Cognitive Impairment¶

• Features  Early gait impairment and personality/mood changes  Slowed processing speed
• Imaging  No hippocampal atropy and presence of confluent white matter hyperintensities on MRI of the brain

Vascular Dementia (VaD)¶

• 10% of all dementia, >60 y/o
  • Higher risk in men and more likely to cause motor symptoms
• Primarily Executive/Cognitive Dysfunction
• Symptoms  Stepwise (not gradual) decline w/focal neurological deficits  Early Executive Dysfunction o 2 Main Types:  A) Multi-infarct Dementia • Abrupt onset, stepwise deterioration • Typically have prominent motor, reflex, visual, and gait abnormalities • Do not involve problems naming objects (Alzheimer’s) • More prominent fluctuation of cognition  B) Binswanger Disease (Diffuse White Matter) • Associated with longstanding hypertension and/or atherosclerosis, diabetes • Diffuse subcortical white matter damage and subacute insidious course • Lacunar infarcts can be seen on MRI • Early: confusion, impaired memory, perception, executive functions • Late: difficulty in judgement and orientation • Apathy, anxiety, psychosis, euphoria, depression, aggression • Urinary incontinence and dysarthria with or without dysphagia, emotional lability o Cerebral infarction and/or deep white matter changes on imaging  Multiple small cerebral infarctions from cardiovascular disorders  No ventriculomegaly/generalized atrophy in early disease
• Treatment
  • Antihypertensives, anticoagulants

Creutzfeldt-Jacob Disease (CJD)¶

o Prion Disease  sCJD (Sporadic): 95% of all, 55-65 y/o  fCJD (Familial): 5% of all  iCJD (iatrogenic) and vCJD (Variant), Younger patients • vCJD caused by mad cow disease • iCJD caused by infected human tissues or hormones o Symptoms  Rapid progression of psychiatric symptoms with anxiety, fatigue, ataxia followed by dementia within weeks  Akinetic Mutism  Pyramidal/extrapyramidal dysfunction  Cerebellar dysfunction, hiccups  Hypokinesia, Startle Myoclonus late in disease course  Circadian rhythm interruption  Cerebellar ataxia, decreased tendon reflexes o Diagnosis: Real Time Quaking-Inducted Conversion Assay of CSF • Most sensitive and specific for prion proteins o Uses recombinant prion protein and thioflavin T, fluorescent dye • Elevated CSF of 14-3-3 regulatory proteins, total tau proteins o Not sensitive or specific enough  Confirmatory: Brain Biopsy  Generalized slowing with periodic, bi/tri phasic sharp wave complexes on EEG, “Triphasic Bursts”  T1/T2 MRI: abnormal diffusion in thalmi, basal ganglia, or cortical ribbon • Increased intensity in the diffusion-weighted sequence in the BG and various cortical regions o Prognosis: fatal in <1 year in >90% of patients o Treatment  None • Alcoholic Dementia o Ethanol Induced Dementia  5-6 drinks a day needed over a lifetime • Hypoxic Encephalopathy • AIDS Dementia Complex o 2% of all dementia, mcc in young patients  Affects half of all AIDs patients not on ART o Cortical and subcortical atrophy and ventricular enlargement  Subacute or chronic cognitive defects, depression, impaired psychomotor ability  Irreversible dementia, subcortical symptoms, Basal ganglia or nigrostriatal dysfunction  Slower movement, difficult smooth limb actions  Related to the degree and duration of immunosuppression o HIV-Associated Neurocognitive Disorders (HAND)  Dementia due to subcortical atrophy, inflammation and demyelination • Basal ganglia or nigrostriatal dysfunction • Can be prevented in HIV but not AIDS  RF: Long standing HIV, Age ≥50, CD4 < 200  Severity (increasing as you go down): • Asymptomatic neurocognitive impairment • Mild neurocognitive disorder • HIV-associated Dementia/Encephalopathy  Symptoms • Impaired memory and attention/concentration, anhedonia o Personality and behavior changes • Decreased alertness, confusion, blunted affect, slowed movement, impaired concentration, generalized atrophy • Movement disorders later (tremor and gait) o Slower movements with substantial cognitive impairment late  Prognosis: Quicker progression, months, life expectancy <1 year  Diagnosis: Clinical, neuropsychological testing • MRI: diffuse increase in white matter intensity o Diffuse atrophy later  Treatment • ART with high CNS uptake • Cortico-Basal Syndrome o Asymmetric posterior frontoparietal degeneration

Traumatic Encephalopathy Syndrome (TES)¶

• Progressive neurodegenerative syndrome with repetitive head trauma
• Emotional dysregulation, behavior change, motor disturbance w/parkinsonian features
  • Memory features largely lacking
• Generalized cerebral atrophy, MRI may be normal