Dementia Non-Pharmacological Strategies

Non-Pharmacological Strategies for Dementia Patients

• Cognitive stimulation therapy enhances cognitive functions.
• Social interaction and activities improve well-being.
• Environmental modifications reduce confusion and improve safety.

Amyloid + Tau Cascade

• Amyloid-beta accumulation: Misfolded amyloid-beta proteins form plaques in the brain, triggering neuroinflammation and oxidative stress.
• Tau hyperphosphorylation: In response to amyloid-beta, tau proteins become hyperphosphorylated, leading to the formation of neurofibrillary tangles inside neurons.
• Neuronal dysfunction: The combined effect of amyloid plaques and tau tangles causes synaptic dysfunction, neuronal death, and progressive brain atrophy.

Symptoms from Brain Damage

• Lateral and posterior areas: (Specific symptom information unavailable)
• Anterior areas: (Specific symptom information unavailable)
• Medial temporal areas: (Specific symptom information unavailable)

Attention in Cognitive Function

• Attention is the cognitive process that selectively focuses on specific stimuli or information. It enhances sensory processing by prioritizing important stimuli and filtering out irrelevant information.
• It operates under both voluntary (top-down) and involuntary (bottom-up) control.

Primary Types of Attention

• Selective attention: Focusing on one stimulus while ignoring others (e.g., listening to one person in a noisy room).
• Divided attention: Processing multiple stimuli or tasks simultaneously.
• Sustained attention: Maintaining focus over a prolonged period (vigilance).
• Alternating attention: Switching focus between tasks or stimuli.

Prefrontal Cortex's Role in Attention

• The prefrontal cortex (PFC), especially the dorsolateral PFC, is responsible for executive control over attention.
• It helps in voluntary focus (top-down control), enabling goal-directed behavior.
• The PFC integrates sensory inputs and helps prioritize relevant stimuli for processing.

Parietal Lobe's Role in Attention

• The parietal lobe, particularly the posterior parietal cortex (PPC), is critical for spatial attention.
• It directs attention to specific locations in space and enhances the processing of stimuli in those areas.
• Damage to the parietal lobe can result in hemispatial neglect, where individuals fail to attend to one side of their environment.

Reticular Activating System (RAS) in Attention

• The reticular activating system (RAS), located in the brainstem, regulates arousal and alertness, essential for attention.
• It prepares the brain to respond to stimuli by maintaining a state of wakefulness and alertness.
• The RAS is crucial for transitioning between sleep, wakefulness, and focused attention.

Neural Networks Involved in Attention

• Dorsal attention network (DAN): Engages the superior parietal lobule and frontal eye fields for goal-directed attention.
• Ventral attention network (VAN): Includes the temporoparietal junction and ventral frontal cortex, responsible for detecting novel stimuli and reorienting attention.
• These networks coordinate to maintain and shift attention based on internal goals and external stimuli.

Treisman's Attenuation Theory

• Treisman's Attenuation Theory suggests that unattended information is not entirely blocked but is attenuated (weakened).
• Information passes through a filter that reduces its strength rather than completely blocking it.
• Attenuated stimuli can still be processed if they are relevant or important (e.g., hearing your name in a background conversation).

Attention Modulating Sensory Processing

• Attention enhances sensory processing by prioritizing relevant stimuli and filtering out irrelevant ones, amplifying neural responses.

Amyloid Cascade Detailed Explanation

• Amyloid Precursor Protein (APP) Cleavage: APP, a transmembrane protein, is cleaved by two enzyme pathways:
  • Non-amyloidogenic pathway: Alpha-secretase cleaves APP, producing non-toxic fragments.
  • Amyloidogenic pathway: Beta-secretase (BACE1) and gamma-secretase cleave APP, producing Aβ peptides (mainly Aβ40 and Aβ42). Aβ42 is more hydrophobic and prone to aggregation than Aβ40.
• Aβ42 Aggregation: Aβ42 monomers aggregate into oligomers, then protofibrils, and eventually form amyloid plaques.
• Plaque Formation: Extracellular deposition of amyloid plaques occurs, primarily in the hippocampus and cortex. These plaques disrupt neuronal communication and trigger neuroinflammatory responses.
• Toxic Effects of Aβ:
  • Synaptic Dysfunction: Aβ oligomers impair synaptic plasticity, inhibiting long-term potentiation (LTP).
  • Neuroinflammation: Activation of microglia and astrocytes causes the release of pro-inflammatory cytokines.
  • Oxidative Stress: Aβ generates reactive oxygen species (ROS), causing neuronal damage.
  • Calcium Dysregulation: Aβ disrupts calcium homeostasis, leading to excitotoxicity.
• Downstream Effects: Aβ deposition promotes hyperphosphorylation of tau, linking the amyloid and tau cascades.

Tau Cascade Detailed Explanation

• Normal Tau Function: Tau is a microtubule-associated protein that stabilizes microtubules in axons, essential for intracellular transport.
• Hyperphosphorylation of Tau: Abnormal activation of kinases (e.g., GSK-3β, CDK5) leads to hyperphosphorylation of tau.
• Hyperphosphorylated Tau Detachment: Hyperphosphorylated tau detaches from microtubules, causing their destabilization.
• Tau Oligomerization and Aggregation: Detached tau proteins aggregate into oligomers, which further polymerize into paired helical filaments (PHFs). PHFs aggregate to form neurofibrillary tangles (NFTs) within neurons.
• Toxic Effects of NFTs:
  • Axonal Transport Disruption: Loss of microtubule stability impairs intracellular transport, affecting synaptic function.
  • Synaptic Loss: Neurons lose their ability to communicate effectively.
  • Neuronal Death: Accumulation of NFTs and related toxic effects lead to apoptosis.
• Propagation of Tau Pathology: Hyperphosphorylated tau spreads trans-synaptically from one neuron to another, propagating tau pathology.

Interaction Between Amyloid and Tau Cascades

• Amyloid Precedes Tau Pathology: Aβ accumulation triggers tau hyperphosphorylation and NFT formation. Aβ toxicity promotes kinase activation, contributing to tau dysfunction.
• Combined Neurotoxicity: Aβ and tau together amplify synaptic dysfunction, neuroinflammation, and oxidative stress. This synergy accelerates neuronal death and cognitive decline.