Does Alzheimer's disease progression damage brain regions responsible for emotional regulation, decision-making, impulse control, and social behavior?

From the Guidelines

Alzheimer's disease progressively damages brain regions responsible for emotional regulation, decision-making, impulse control, and social behavior, leading to significant morbidity and decreased quality of life. As the disease advances, it causes significant neurodegeneration in key areas including the prefrontal cortex, which manages executive functions and decision-making; the amygdala, which processes emotions; and the hippocampus, which affects memory and emotional responses. These changes explain why patients often experience personality changes, emotional dysregulation, impaired judgment, and inappropriate social behaviors as the disease progresses, as noted in guidelines for managing Alzheimer's disease 1. The damage occurs through accumulation of amyloid plaques and tau tangles that disrupt neural connections, leading to cell death in these critical regions. Neuroimaging studies have demonstrated reduced volume and activity in these brain areas correlating with behavioral symptoms. Additionally, disruption of neurotransmitter systems, particularly acetylcholine, serotonin, and dopamine, further impacts emotional and behavioral regulation. These physiological changes explain why many Alzheimer's patients develop symptoms like apathy, agitation, depression, anxiety, and loss of social awareness as the disease advances beyond its initial memory impairments. Some key points to consider in managing these patients include:

• Assessing patients periodically for agitation, depression, and psychotic symptoms, because behavioral problems become common as the disease progresses 1
• Evaluating patients for drug toxicity and medical, psychiatric, psychosocial, or environmental problems that may underlie behavioral changes 1
• Including potentially useful nonpharmacologic interventions in the care plan, as well as adequate precautions to reduce the risk of harm to the patient and others 1
• Managing behavioral symptoms, such as agitation and wandering, which become common as Alzheimer’s disease progresses 1
• Assessing daily function, cognition, comorbid medical conditions, disorders of mood and emotion, and caregiver status in patients with Alzheimer’s disease 1

From the Research

Alzheimer's Disease Progression and Brain Region Damage

• As Alzheimer's disease progresses, it damages brain regions responsible for managing emotions, decision-making, impulse control, and social behaviour 2.
• The cerebral cortex, a vulnerable brain region, is implicated in memory, emotion, cognition, and decision-making behavior, and is damaged in Alzheimer's disease 2.
• The disease is characterized by progressive neuronal loss, with apoptosis and necroptosis activated at different stages of the disease 2.

Cognitive and Functional Symptoms

• Alzheimer's disease affects cognitive function, leading to memory loss and impairment in activities of daily living 3.
• The disease also affects functional symptoms, with treatments available to manage symptoms, including pharmacologic management and nonpharmacologic interventions 3.
• Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, are able to stabilize or slow decline in cognition, function, behavior, and global change 4.

Neurodegenerative Benefits of Acetylcholinesterase Inhibitors

• Acetylcholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, have anti-neurodegenerative benefits in Alzheimer's disease, with the potential to slow disease progression 5.
• These inhibitors enhance acetylcholine-dependent release and uptake of nerve growth factor, sustaining cholinergic neuronal viability and delaying dementia progression 5.
• Irreversible acetylcholinesterase inhibitors may produce higher levels of CNS inhibition, leading to greater therapeutic benefits 5.