NCDs + Delirium

Key differences/prominent sxs of all the NCDs

Cortical:

Alzheimer’s: learning/memory

Frontotemporal: behavioral (social/EF + 3 personality) or language/aphasia variant (primary progressive aphasia)

Cortico-subcortical:

Lewy bodies: complex attention/EF + visuospatial (visual hallucinations); any motor sxs (parkinsonism) come after/coincide with cognitive; suggestive (REM sleep bx disorder, NMS)

Prion disease/CJ disease: highly contagious, very rapid progression (e.g., 6 months), Prion = motor disease

Subcortical: sloooowing down of motor + thought + feeling

Parkinsons’s: motor sxs first

Huntington’s

HIV infection

Vascular NCD

Best neuroimaging technique for distinguishing NCD d/t Alzheimer’s vs. other NCDs

FDG-PET (glucose metabolism in brain)

Delirium dx

-Sudden onset (few hrs/days) disturbance in attention and awareness, that comes and goes during the day

-AND 1+ cognitive disturbance (e.g., memory, language)

*cannot be d/t NCD, or occur during coma/severe underarousal

*must be a direct consequence of medical issue (e.g., TBI, drugs, withdrawal, fever, medical condition)

Delirium is most common in…

-hospitalized older adults

Causes of delirium

-high fever, nutritional deficiency, electrolyte disturbance

-head injury

-certain drugs

• alcohol, sedatives, anticholinergic drugs

• lithium

-kidney (renal) or liver (hepatic) failure

Treatment of delirium

1.) Address medical condition leading to delirium

2.) Change environment to reduce disorientation (light therapy, reduce noise, fewer people)

3.) If agitation, or psychotic sxs → haloperidol or other antipsychotic

What is NCD?

-Acquired dysfunction in 1+ cognitive area (not neurodevelopmental)

e.g., memory, social cognition

Mild vs. Major NCD

Major = significant decline in 1+ cognitive area that interferes with daily independence

Mild = modest decline, does NOT interfere with daily independence (w/ effort, compensatory strategies)

*NCD ≠ delirium, cognitive decline isn’t only d/t delirium

Cortical NCDs (damage where, names)

Damage in cerebral cortex

-NCD d/t Alzheimer’s

-Frontotemporal NCD

Initial sxs of cortical NCDs

-most often = memory loss

-aphasia, agnosia (language centers)

-impaired insight, judgment (PFC)

-apraxia (motor cortex)

Subcortical NCD (damage where, names)

Damage in basal ganglia, thalamus, and brainstem

-NCD d/t Huntington’s, Parkinson’s

-NCD d/t HIV infection

-some vascular NCDs

Primary sxs of Subcortical NCDs

(Slooowing down of motor, thought, and feeling)

-psychomotor retardation – e.g., impaired gait, dysarthric speech (speech affected d/t motor impairments)

-slowed cognitive processes (areas that filter – BG and thalamus)

-apathy, depression

Cortico-subcortical NCDs

Damage in connections btwn cortical + subcortical areas

-NCD w/ Lewy bodies

-Prion/Creutzfeldt-Jakob disease (a type of NCD due to prion disease)

-Some vascular NCDs

Sxs depend on areas damaged

Alzheimer’s demographics (age of onset, gender, race)

-Avg sx onset: 70s-80s, prognosis = 8-10yrs (from sx onset to death)

-Early-onset = 50s (linked to chromosomal mutations)

-More common in women (but could be bc W outlive M)

-Race: in adults 65+, most common in Black people, then Hispanic

Alzheimer’s diagnosis

-only definitive with brain biopsy (but rarely done bc risky and uncomfortable)

-Probable = genetic mutation confirmation

-Possible major NCD d/t A = learning/memory + 1 cognitive domain impacted (but not progressive/gradual or mixed etiology)

-Possible minor NCD d/t A = full Alzheimer’s pattern (memory/learning decline + decline is progressive/gradual + no mixed etiology–e.g., stroke)

One of the genetic variants that increase risk for Alzheimer’s

ApoE4 variant on chromosome 19

Neurotransmitters involved in Alzheimer’s

-low ACh, high glutamate (gluatamate excitotoxicity)

^both ACh and glutamate are involved in learning/memory

Hallmark brain abnormalities of Alzheimer’s

(AP + NT + LC)

1.) Extracellular Amyloid plaques – clumps of beta-amyloid protein in btwn neurons (formed from APP/amyloid precursor protein)

2.) Intracellular Neurofibrillary tangles – accumulated tau protein that forms threads, then tangles inside neurons

APs + NTs disrupt neuronal communication

3.) Locus coeruleus – part of the pons

Brain areas first impacted by AP + NT buildup

1.) Locus coeruleus – neuronal loss; waaaay before sxs appear

2.) Medial temporal lobe (entorhinal cortex, hippocampus, amygdala)

Then spreads to frontal/parietal lobes

Loss of sense of smell is…

-Strong indicator of later Alzheimer’s or Mild Cognitive Impairment

-greater impairment → greater cognitive impairment

(Medial temporal lobe is involved in olfactory processing)

Neuronal loss in the locus coeruleus is linked to → (disorders)

Alzheimer’s

Parkinson’s

NCD with Lewy bodies

Risk factors for Alzheimer’s (other disorder, personality traits, sensory loss)

-Down Syndrome (Standard trisomy 21) = extra chromosome 21 → extra APP gene (amyloid precursor protein)

-high neuroticism + low conscientiousness ←→ more amyloid and tau deposits

-low educational attainment

-hearing loss

Early stage of Alzheimer’s

(2-4 yrs)

-ST memory loss (usually 1st sx)

-anomia – difficulty recalling names of familiar people/objects

-personality change (apathy, loss of spontaneity)

-impaired attention and concentration, poor judgment

-time/space disorientation

-anxiety, depression

Middle stage of Alzheimer’s

(2-10 yrs)

-increasing ST memory loss + LT memory loss

-mood more labile, disorientation increased

-delusions + hallucinations, wandering + pacing

-perseveration

-sundowning (increased confusion, agitation, restlessness with sunset)

-ADL difficulties

Late stage Alzheimer’s

(1-3 yrs)

-loss of basic motor skills

-loss of ADLs (all or most)

-seizures, abnormal reflexes

-urinary/fecal incontinence

Alzheimer’s Tx

-no cure (increase ACh, reduce glutamate; reduce APs)

1.) Cholinesterase inhibitors (increase ACh)

• Donepezil – only med approved for severe Alzheimer’s

• Rivastigmine, Galantamine

2.) Memantine – NMDA receptor antagonist (decrease glutamate)

3.) Donanemab – recently FDA-approved monthly IV infusions that reduces amyloid plaques

Standard therapeutic txs for Alzheimer’s

CBT – to improve cognitive fx, reduce problem bxs

Antidepressants, anxiolytics, antipsychotics – for depression/anxiety/mania/psychosis

Caregiver support and skills training

Pseudodementia (vs. Alzheimer’s)

-depression with prominent cognitive sxs

-responds well to tx

-abrupt onset (not insidious)

-often respond to assessment Qs with IDK (vs. answering incorrectly)

-overestimate/exaggerate cognitive difficulties (vs. denied/minimized in Alzheimer’s _

Frontotemporal NCD (prominent sxs)

-Behavioral variant:

• social cognition (socially inappropriate bx) OR EF (ADHD-like sxs)

• 3+ personality changes (socially disinhibted bx; loss of empathy/sympathy; hyperorality or hyperphagia, perseverative/stereotyped/compulsive bx)

-Language variant (primary progressive aphasia)

Semantic, Agrammatic/nonfluent, and Logopenic Frontotemporal NCD

Semantic – (meaning) comprehension impaired

Agrammatic/nonfluent – grammar, hesitant effortful speech

Logopenic – (alogia, loss of speech) word finding, sentence repetition impaired

NCD with Lewy bodies (what is it + diagnosed when?)

-build of abnormal protein clumps (Lewy bodies) in brain

-minor/major NCD present

-Probable (2 core features) or Possible (1-2 core/suggestive features) form

-insidious onset + gradual progression

NCD with Lewy Bodies (3 core features)

Early prominent cognitive sxs:

1.) Visuospatial (visual hallucinations)

2.) Complex attention + EFs (fluctuating cognitions, with variable attention and alertness)

Motor/parkinsonism sxs often come after cognitive:

3.) Parkinsonism sx (TRAP)

NCD with Lewy Bodies (Suggestive features)

1.) REM sleep behavior disorder sxs

2.) severe Neuroleptic (antipsychotic) sensitivity

Difference btwn NCD d/t Alzheimer’s vs. NCD d/t Lewy bodies

Alzheimer’s: prominent early cognitive sxs = learning/memory

Lewy bodies: prominent early cognitive sxs = EF/complex attention + visuospatial

NCD d/t Prion disease (prominent sxs, most common type)

Prion = CJD = mad cow (motor sxs, cerebellum/ataxia)

-insidious onset, highly contagious, very rapid progression

Creutzfeldt-Jakob disease sxs: (THINK MAD COW)

-motor: ataxia, myoclonus, chorea

-cognitive sxs: confusion/disorientation

-mood: apathy, anxiety, mood swings

Sporadic, Familial, and Acquired Creutzfeldt-Jakob disease

Sporadic CJD – unknown etiology, most common type of CJD

Familial CJD – inherited

Acquired CJD:

• variant CJD – mad cow disease, acquired through eating infected meat

• iatrogenic CJD – blood transfusion, contaminated medical equipment

NCD d/t HIV infection (most prominent sxs)

Subcortical NCD (slooowing down of motor, thought, feeling)

-motor: psychomotor retardation clumsiness, tremors

-thought: cognitive slowing, forgetfulness, impaired attention and concentration

-feeling: apathy, social withdrawal

Vascular NCD

-when major/mild NCD + hx of cerebrovascular disease (stroke, untreated hypertension)

-impacts complex attention/EF (←→ cerebrovascular issues)

Vascular NCD Tx

-focuses on targeting etiology and reducing risk (hypertension, heart disease, diabetes, obesity, high cholesterol, smoking)

NCD d/t another medical condition

-NCD progression ←→ medical condition progression

-NCD may be reversible if medical condition treated (hypoxia, infections, endocrine disorders, poisoning, nutritional deficiencies)

-but some are ireversible