Cognitive Issues in Older Adult- part 1

sensory memory

• Input from the 5 senses; can be ignored or perceived and transferred to short memory in <1 sec

• Stable except for sensory impairment that may occur with age
  (eg, visual loss)

• Initial input to sensory areas of the brain and then processed by hippocampus

short term memory

• Limited capacity, Temporary recall, Processed in 10– 15 seconds long- term storage or decay

• Stable, but may require more effort to encode before decay.

• Prefrontal cortex
  

implicit (procedural)

• Subconscious influence of previously encountered information on
  subsequent performance, Automatic, rote

• Stable (e.g., remains intact until late in a cognitive disease state)

• Cerebellum, putamen, caudate nucleus, and motor cortex

explicit (declarative) semantic

• structured facts, meanings, concepts, and knowledge

• gradual and linear decline acorss lifespan, primarily associated with encoding and retrieval

• prefrontal and temporal cortex

explicit (declarative) episodic

• autobiographical events, contextual knowledge, associated emotions

• gradual and linear decline across lifespan primarily associated with encoding and retrieval

• hippocampus connects various sensory areas of brain to create episode that is consolidated to one event

types of delirium

hyperactive, hypoactive, mixed

• Associated with increased LOS, prolonged recovery times, institutionalized care
• Increased morbidity and mortality rates

delirium patho

• brain structural changes (cortical atrophy, white matter lesions, etc)
• neurotransmitter disturbance in central cholinergic and adrenergic
pathways
• elevated inflammatory cytokines (IL-6, IL-8)
• multifactorial in older adults

what drugs are linked to delirium?

psychoactive agents, anticholinergics, narcotics

what commonly occurs with alzheimers?

depression

pseudodementia

apparent intellectual decline that stems from lack of energy or effort
• Forgetful, move slowly, low motivation, mental slowing
• Responds well to depression treatments

distinguished from dementia:

• More rapid decline in mental function than AD or other type of dementia
• Usually not disoriented
• Difficulty with concentrating but less difficulty with STM
• Writing, speaking, and motor skills usually are not affected
• More likely to comment on memory problems

when is depression more common in dementia?

early to moderate stages

increased severity dementia = decreased prevelance of major depression

theory that depression is risk factor for dementia

damage to hippocampus from hypercortisolemia

what may contribute to cognitive impairment?

Tricyclic antidepressants, diagnosis of cognitive impairment

dementia

• A clinical syndrome of cognitive and functional decline, usually of a chronic or progressive nature

• Cognitive deficits that cause significant impairment in occupational or social functioning that is a decline from previously higher-level
  functioning

what is dementia diagnosed through?

semi structured interview, detailed medical and neurologic exam, neurocognitive testing

what does dementia impact?

• intellectual functioning

• memory

• abstract thinking, judgment & language, ID of people & objects, personality changes, ability to use object appropriately

aging brain - dementia

• Notable decline in memory for recent events, decline in ability to converse
• Gets lost in familiar territory while walking or driving, may take hours to eventually remember

• Becomes unable to operate common appliances, unable to learn to operate even simple appliances
• Abnormal performance on mental status exams not accounted for by education or cultural differences

vascular dementia key features

• Associated with Cerebrovascular disease
• More often abrupt onset, but can be gradual with small vessel disease
• Memory loss usually less severe than AD
• Mood changes and apathy common
• Can occur in conjunction with AD = mixed dementia

what is a subset form of vascular dementia?

multi infarct

what are the affected brain areas with vascular dementia?

• medial temporal atrophy

• cortical and subcortical lesions

clinical symptoms of vascular dementia

• Impaired attention, planning
• Difficulties with complex activities
• Disorganized thought

lewy bodies dementia key features

• Complex visual hallucinations
• Parkinsonism
• Sleep disturbances
• Autonomic symptoms (i.e., hypotension)
• Fluctuating cognition

what can occur in conjunction with PD?

dementia with lewy bodies

what brain areas are affected with lewy bodies?

• Less severe medial temporal lobe atrophy than AD
• FDG-PET shows occipital hypoperfusion and hypometabolism
• Loss of dopaminergic neurons in substantia nigra
• Limbic
• Brainstem
• Neocortex

frontotemporal dementia key features

• More common in younger groups (50-60 yr old)
• Memory often intact in early stage
• Significant changes in behavior and personality
• Disinhibition and impulsiveness are common

what types of frontotemporal dementia are there?

• picks disease

• progressive supranuclear palsy

• corticobasal degeneration

what brain areas are affected with FTD?

• frontal and temporal lobes

• specific areas of atrophy dependent on type of variant

alzheimers key features

• Gradual loss of memory and function leading to total dependence on caregivers
• Eventual inability to recognize family/friends/self

what brain areas are affected with alzheimers?

• Entorhinal area
• Hippocampus
• Amygdala
• Regions of neocortex

neurobiological changes of cognitive dysfunction

• Asymptomatic to mild cognitive impairment stages: amyloid markers are most prominent change; shifts to more prominent structural changes once MCI stage begins
• The degree of atrophy of medial temporal structures → potential diagnostic marker for mild cognitive impairment stage of AD

what areas of the brain are most affected by dementia, specifically AD?

memory and language

healthy brain vs. AD

• Communication signals between brain cells diminish
• Metabolism impaired with development of neurofibrillary tangles
• Repair disabled by amyloid plaques
• Plaques and tangles produce mistakes throughout the brain resulting in cell death

what are the 3 stages AD progresses on?

• preclinical

• MCI

• alzheimer’s dementia

amyloid hypothesis

• Aggregation of amyloid beta → Tau-tangle formation → Inflammation
→ Synapse dysfunction and cell death → Dementia

is amyloid beta good or bad?

can play a beneficial role but excess amounts impact brain function

apoE function in liver

transport lipids and maintain cholesterol homeostasis

apoE function in brain

• Level of Aβ
• Brain lipid transport
• Glucose metabolism
• Neuronal signalling
• Neuroinflammation
• Mitochondrial function

apoE 4 carriers

• promote aggregation and stabilizes AB oligomers (promotes AB buildup) → further degradation of AD

what does apoE 4 affect?

gamma secretase → AB production enhancement

• impairs lysosomal degradation of AB, less able to transport AB across BBB

tests to detect level of amyloid beta

• PET scans - amyvid, vizamyl, neurasaq

• 23andMe at home test - ID apoE variant

acetylcholine

dramatic reduction from neuron degeneration

loss of 60-90% of ach activity = memory impairment

symptomatic tx

◦ Blocking acetylcholinesterase
◦ Medications targeting NMDA pathway

medications - mild

cholinestersae inhibitor

medication - moderate

• cholinesterase inhibitor + memantine more likely to delay progression

• address behavioral and psychological symptoms

medication - severe

◦ Consider if medication will provide a benefit, possibly due a med-free trial
◦ May continue cholinesterase inhibitor approved for late-stage disease or memantine

cholinergic AE

GI issues (NVD)

what can memantine cause?

dizziness - watch for falls

lecanemab (Leqembi)

blocks formation of β-amyloid plaques from the brain
• IV infusion over 1 hour every 2 weeks
• $26,500/year
• Does not factor in costs for healthcare providers, infusion center, MRIs
• Medicare will reimburse for patients diagnosed with MCI or mild AD

lecanemab AE

• ARIA-edema, headaches, ARIA-microhemorrhage, ARIA-H superficial siderosis, diarrhea,confusion/delirium, and falling
• ARIA: amyloid-related imaging abnormalities seen on MRI
• Patients who have 2 APE 4 alleles have higher incidence of ARIA