neurocognitive disorders

myths about late life

Aging involves inescapable cognitive decline o Severe cognitive problems do not occur for most • Older adults are unhappy o More skilled at emotion regulation o Attend more to positive o Display less psychophysiological response to negative emotion • Late life is a lonely time o Social selectivity. • Interests shift away from seeking new social interactions to cultivating a few close friendships

polypharmacy

40% of elderly people are prescribed with 5+ medications

• increases risks of various drug reactions (research of drugs is done on young people)

the silver/dementia tsunami

A huge increase in the aging population, meaning that theres an increasing risk of mental disorders which can increase

• Healthcare demand

• Dementia and chronic illness

• Social services and caregiving needs

dementia

umbrella term for disorders in change of in brain functioning that interfere with daily functioning

mixed dementia

abnormalities characteristic of more than one type of dementia occur simultaneously.

most common dementia symptom and secondary psychiatric symptoms

most commonly:

diminished memory (usually recent memories)

secondary:

• sleep disturbances

• depression

• delusions and hallucinations

• difficulty with impulse control

what is young onset dementia

dementia patients before the age of 65

most often FTD

lack of specific care as facilities are focused on elderly

Leading theory for development of AD

amyloid cascade theory:

abnormal accumulation of amyloid beta protein in the brain triggers a chain of events that leads to alzheimers disease

1. usually amyolid beta proteins are cleared from the brain

2. in AD these proteins misfold and accumulate, forming plaques, happing outside the neurons

3. these plaques disrupt neuron to neuron communication, which causes the formation of neurofibrillary tangles (clumps of tau proteins inside of the neuron)

4. this causes neuron dysfunction, and eventualy leads to neurodegeneration

5. leads to atrophy in the hippocampus and cortex

Markers of AD pathology

• shrinking of gyri (curves outwards) and widening of sulci (curves inwards)due to neurons dying

• widening of fluid-filled ventricles

• Hippocampus atrophy (cells shrink)

healthy vs AD brain weight

healthy:1400g

AD:900g

disease stages of alzheimers disease

• Pre-pathology: No brain changes yet.

• Asymptomatic: Brain changes start (plaques/tangles), but the person functions normally.

• Subjective complaint: Person notices cognitive changes, but testing shows no deficits.

• Mild cognitive impairment (MCI): Objective impairment in one domain (like memory), but daily functioning is still preserved.

• Dementia: Multiple domains impaired and daily life is affected

Normal → SCI → MCI → Dementia

• SCI (Subjective Cognitive Impairment):

  • The person complains of memory/thinking issues.

  • No objective evidence of impairment on tests.

• MCI (Mild Cognitive Impairment):

  • Clear impairment in one cognitive domain (e.g., memory or language).

  • Daily activities are still mostly intact.

• Dementia:

  • Impairment in multiple domains.

  • Interferes significantly with independent living.

neuropsychological assessment

tests for:

• global cognition

• attention- focus and shifting tasks

• memory- leaning and recall

• executive functioning- problem solving, planning

• language-naming, understanding

• visuocontruction

global cognition

mini-mental state examintation (MMSE):
- 30 point test

• test memory, attention, language at a basic level

attention testing

A trail making test to see attention and shifting skills

numbers: 1, 2, 3 ,4, 5, etc…

mixed: 1, A ,2, B 3, C

memory testing

auditory verbal learning test

repeated word lest are read outloud, and memory is tested

executive function

Stroop test

naming the color of ink a word is printed in, not reading the word

tests inhibition and cognitive control

visuocontruction

clock drawing

amyloid pet imaging

detects the amount of amyloid beta plaque in the brain, which is a marker for alzheimers

CSF biomarkers

low amyloid beta: means there more in the brain

high tau proteins: signify neuronal damage

MRI biomarkers

detects brain shrinkage, especially in hipppocampus

is a marker for neurodegeneration

biomarker timeline (Jack model)

• Amyloid-β (Aβ): Abnormal first—starts in Subjective cognitive impairment stage.

• Tau/neuronal injury: Next—starts in late SCI or early Mild Cognitive Impairment.

• Brain structure (atrophy): Detected with MRI during MCI.

• Memory & function: Clinically noticeable during MCI/Dementia.

current treatment for dementia

acetylcholinesterase inhibitors:

• IN AD, neurons produce less acetlychonie, which has a role in memory and leaning

• these drugs will block the breakdown of acetlycholine, to boost its levels

NMDA receptor agonists:

• AD leads to excess glutamate, causing too much calcium to enter neurons, which speeds up damage

• this drug recudes the calcium overload

important: these are treatments not cures!

critique of amyloid cascade hypothesis

• amyloid beta plaques are seen in older people without dementia

• Plaque burden doesn’t correlate well with symptom severity

• drugs that target amylod plaques have had disappointing results

Lecanemab Drug Trial

tried a drug againt amyloid plaques

• there was a asignificant drop in plaques vs placebo

• there was a slower cognitive decline, but still declining

Sperling prevention framework

primary prevention: shop the amyloid plauques from forming

secondary prevention: reduce AB burden before symptoms arise

tertiary prevention: Slow down cognitive decline via neuroprotection and neurotransmitter support