BH E3- Neurocognitive disorders

The following DSM-5 criteria is for what condition?

• significant cognitive decline ≥1 cognitive domains

  • complex attention, executive function, learning and memory, language, perceptual motor, social cognition

  • decline based on concern of individual, knowledgeable informant, or clinician and

  • substantial impairment in cognitive performance, documented by testing / clinical assessment

• interferes w/ independence

• deficits do not occur exclusively during a delirium

• not better explained by other disorder

Neurocognitive disorder

What kind of NCD is associated with the following presentation?

• cognitive decline: memory loss early, impairments in language, orientation & social behavior

• psych sx: depression, anxiety, sleep disturbances

• ± behavioral disturbances

• amyloid plaques

NCD due to Alzheimer's

The following DSM-5 criteria is for what condition?

• significant cognitive decline ≥1 cognitive domains

  • complex attention, executive function, learning and memory, language, perceptual motor, social cognition

  • decline based on concern of individual, knowledgeable informant, or clinician and

  • substantial impairment in cognitive performance, documented by testing / clinical assessment

• interferes w/ independence

• deficits do not occur exclusively during a delirium

• not better explained by other disorder

Neurocognitive disorder

What kind of NCD is associated with the following presentation?

• cognitive decline: memory loss early, impairments in language, orientation & social behavior

• psych sx: depression, anxiety, sleep disturbances

• ± behavioral disturbances

• amyloid plaques

NCD due to Alzheimer's

How does NCD due to Alzheimer’s disorder onset & progress?

Insidious onset & gradual progression in ≥2 domains

*course 1-20 yrs, avg 10yrs from dx to death

The following RF are for what condition?

• risk doubles every 5 years after age 65

• Fhx- inc risk 2-3x

• lower education/ low cognitive reserve

• head trauma, vascular events

• chemical exposure- heavy metals, toxins

• APOE allele e4 - inc risk ~2.5x

  • e2 is protective, e3 is neutral

NCD due to Alzheimer’s

What genetic mutations & biomarkers may be present in NCD due to Alzheimer’s?

Presenilin 1 (chrom 14) & presenilin 2 (chrom 1) are proteases that misprocess APP (chrom 21)

Biomarkers: hyperphaosphorylated tau, neurofilament light chain, GFAP

What medications slow progression in NCD due to Alzheimer’s?

Cholinesterase inhibitors: Donepezil, galantamine, rivastigmine

NMDA antagonist: Memantine

Monoclonal ab: Aduhelm, leqembi, possibly donanemab

*preferred combo → cholinesterase + memantine

What are medication considerations for treatment of Alzheimer’s?

Try non-pharm mgmt first, start meds early in disease course & continue long term (don’t interrupt), modest benefits- may not see cognitive gains but behavioral sx improve

What are alternative approaches to treatment of Alzheimer’s?

*less evidence based

Axona, ginko biloba, NSAIDs, statins, vit E, antioxidants

What causes neuronal damage and death seen in Alzheimer’s?

Excess glutamate overstimulates NMDA receptors → excess Ca influx

What is the MOA of memantine in the treatment of alzheimers?

Block NMDA receptor over activation → reduce exictotoxicity & slow cognitive decline

What is the MOA of cholinesterase inhibitors (donepezil) in the treatment of Alzheimer’s?

Inhibit breakdown of ACh → inc availability in synaptic cleft → improve attention & cognitive function by enhancing cholinergic transmission

What is the MOA of rivastigmine in the treatment of Alzheimer’s?

Inhibits both ACH & BChE

*also approved for treatment of parkinson’s disease dementia

What was the first approved cholinesterase inhibitor that was withdrawn due to hepatotoxicity?

Tacrine (Cognex)

How are amyloid protein plaques evaluated in NCD due to Alzheimer’s?

PET can w/ radioactive tracers

*also CT, MRI, fMRI, SPECT

What are the core features of NCD due to Lewy body & Parkinson’s disease?

Fluctuating cognition- episodes of confusion / unresponsiveness lasting hrs-days, Visual hallucinations, Parkinsonian motor sx, REM sleep behavior disorder, Marked sensitivity to antipsychotics (neuroleptics)

NCD due to Lewy Body dementia or Parkinson’s disease?

• Parkinsonism and cognitive symptoms occur w/in 12 mos of each other

Lewy body dementia

NCD due to Lewy Body dementia or Parkinson’s disease?

• Parkinsonian symptoms precede dementia by > 12 mos

Parkinson’s disease

What are abnormal protein aggregates (ubiquitin, neurofilaments, synuclein) found in nerve cells?

Lewy bodies

Lewy body dementia progresses ________ than alzheimer’s/

Faster

What is the treatment for NCD due to Lewy body dementia or parkinson’s disease?

Preferred: Cholinesterase inhibtors → Rivastigmine patch

*use parkinson’s meds cautiously

What should be avoided in Lewy body dementia & parkinsons?

Anticholinergics (worsen cognition) & antipsychotics (inc sensitivity & worsen sx)

What kind of NCD has the following presentation?

• Step wise pattern of memory / functional decline

• Focal neurological signs

• Comorbid problems: HLD, homocysteine, smoking, AF, DM, etc

• Multiple infarcts on CT

NCD due to vascular disorders

What condition associated with alcohol use encompasses ophthalmoplegia, ataxia, & mental confusion?

Wernicke’s encephalopathy

What condition associated with alcohol use encompasses severe difficulty to learn new information, difficulty to recall remote memory, & confabulations?

Korsakoff’s syndrome

What kind of NCD?

• Vitamin B1 deficiency

• atrophy of maxillary bodies & dorsal medial nucleus of thalamus

• wernicke’s encephalopathy or karsakoff’s syndrome

NCD due to alcohol use

What is the treatment for NCD due to alcohol use?

Thiamine

*give before dextrose to avoid central pontine hemorrhages

What type of NCD has the following presentation?

• Language & personality changes before memory problems

• impulsive, silly, inappropriate behaviors, behavioral disinhibition

• apathy, inertia, hyperoralities

• changes in executive functions but preservation in behavior & speech

• rapid course

• pick bodies (previously Pick’s disease)

NCD due to frontal-temporal disorder

What are large Tau protein accumulations?

Pick bodies

Alzheimer's or FTD?

• Memory (temporal lobe) → language (frontal lobe) → orientation (parietal lobe)

Alzheimer’s

Alzheimer’s or FTD?

• Language (frontal lobe) → memory (temporal lobe) → orientation (parietal lobe)

FTD

What is the triad of symptoms for NCD due to NPH?

Dementia, gait disturbances, incontinence

What is the treatment for NCD due to NPH?

VP shunt

What kind of NCD?

• autosomal dominant → presents earlier & more aggressive with each generation

• chrom 4 - longer CAG tripepetide (glutamate AA) tail → more severe symptoms (normal 7-35 repeats)

• SX: involuntary chorea movements, cognitive impairments, psychiatric problems

• *genetic counseling & symptomatic tx

NCD due to Huntington disease

What kind of NCD?

• Prion disease → usually fatal

• rapid onset

• EEG → fast polyphasic waves

• confirm with CSF

• variants: bovine spongiform encephalopathy

NCD due to Creutzfeld-Jakob disease

Delirium or dementia?

• Acute, fluctuating course

• Impaired attentiveness

• Hallucinations & delusions

• Changes over course of a day

• identify and treat underlying cause

Delirium

Delirium or Dementia?

• Insidious onset, stable & slow progression

• Clear sensorium

• Primarily memory issues

• Identify and tx underlying cause

Dementia

What are possible causes of delirium?

Anticholinergics, intoxications, withdrawals, hypoxia, head trauma, hyponatremia, sensory deprivation, UTI, uremia, PNA, hip fx, post surgical in elderly, etc

Dementia or pseudodementia?

• makes attempts to answer / do

• may not change with medication

• memory problems first

• may not complain about memory problems

Dementia

Dementia or pseudodementia?

• does not make attempt - “don’t know, I can’t”

• improves with antidepressants

• depression sx first

• excessive concern or exaggerates memory problems

Pseudodementia

What screening tools are available for NCD?

MMSE (not diagnostic but tracks progression)

Clock drawing (increases sensitivity of MMSE)

MoCA (screening)

What should be avoided in geriatric patients with dementia and agitation due to increased risk for falls & respiratory / urinary infx?

Antipsychotics

How should dementia and agitation be handled?

Speak clear, slow & loud, use on instruction at a time, use bigger fonts if reading, pet therapy, reminiscent therapy, music therapy

*think of treating elderly as small child w/ behavioral issues (dont use haldol)

What should be done for caregivers to NCD patients?

Inquire into their stress & what help they need, respite care (relief), support groups, adult day programs, evaluate mood disorders, recommend 36 hour day (book resource)