Introduction

Alzheimer’s Disease (AD) is a rather common, progressive neurodegenerative condition that damages the brain, causing memory loss and a decline in cognitive function, resulting in abnormal understanding and behaviour. It can be inherited genetically and is caused by the buildup of faulty amyloid beta fragments in the brain, which leads to plaque formation, the breakdown of normal cellular processes and cell death in the affected areas, often parts of the brain associated with memory^.1

Klüver-Bucy Syndrome (KBS), on the other hand, is a rare brain disorder, not caused by plaques, that presents similar symptoms such as memory loss, as well as emotional and behavioural problems. This is caused by damage to the temporal lobes, in particular the hippocampus and amygdala, which are important in forming new memories and controlling emotion and behaviour, often by stroke or a traumatic brain injury^.2

The brain’s vast array of functions is localised to specific areas. Several processes that affect the hippocampus cause AD and KBS. Since the hippocampus is a vital key in storing memories and forming new ones, both conditions present symptoms of memory loss.^{1, 2}

This article discusses the neurological signs and features of these two conditions that overlap and the similar symptoms they share related to neurodegeneration and behaviour. Understanding the differences between the two conditions is crucial for explaining what causes the symptoms in both, as well as new diagnostics and creating targeted treatment strategies in similar neurodegenerative disorders.

Pathophysiology of alzheimer’s disease

AD is a progressive neurodegenerative disorder that is the most common form of dementia and makes up more than two-thirds of dementia cases in those over 65 years old. AD currently affects approximately 55 million people worldwide and is predicted to rise to over 150 million people by 2050. It is also the cause of death for more than one-fifth of Americans over the age of 65.³ This is mainly a genetic condition that you are likely to inherit from your parents have the APOEε4 gene.¹

This brain condition is caused by two normally harmless proteins in the brain: the amyloid beta protein and tau proteins, which become harmful when there are too many of them.

Abnormally high levels of the sticky amyloid beta fragment clump together and become plaques, which build up between nerve cells. They block the communication between cells, triggering neuroinflammation that damages the neuron. When tau protein levels are high, they become tangled together inside nerve cells, blocking signals and cellular transport, removing debris and allowing nutrients to pass through over time, which leads to cell death.¹

The first areas of the brain to be affected by AD are the hippocampus and entorhinal cortex, and other areas of the limbic system, which are involved in memory formation. As AD progresses, it spreads to areas such as the cerebral cortex, which is significant for language, reasoning, and decision-making.⁴ This leads to symptoms forming, such as¹:

• Gradual memory loss
• Decline of thinking and reasoning
• Decline in speaking
• Behaviour and personality/emotional issues such as depression, irritability, and becoming withdrawn
• Reduced functional abilities, such as coordination, spatial understanding, and performing everyday tasks, affect the quality of life for patients.

Pathophysiology of klüver-bucy syndrome

KBS is a rare brain disorder caused by lesions (damage) to your temporal lobes, including the hippocampus and amygdala, which are key in controlling memory, emotion, and behaviour.² The condition is so rare that it is unknown exactly how many people have this condition, with only a handful of people diagnosed with it. Only 26 cases in children have been reported, and it is likely to affect fewer than 1 in 100,000 people⁵.

Damage to these brain areas in KBS is often caused by stroke or a traumatic injury to the brain (TBI). It can also be a result of AD or other serious viral infections such as herpes simplex virus (HSV) or tuberculosis, and causes symptoms such as memory loss and uncontrollable emotional and behavioural problems that include:²

• Memory problems, including dementia and amnesia
• Emotional and behavioural issues, such as getting distracted and not feeling angry or fearful
• Inability to recognise familiar people or objects (visual agnosia)
• Compulsive eating (hyperphagia) and eating disorders
• Compulsive smoking or drinking alcohol
• Putting objects in the mouth and excessively licking things (hyperorality)
• Eating inedible objects (pica)
• Extreme sex drive (hypersexuality)
• Seizures

Links between symptom overlap and neurodegeneration

AD and KBS  are very different conditions, as one is due to neurodegeneration and the other is associated with physical injury, which affects the same brain areas, so some symptoms overlap between the conditions. This damage mainly happens in the hippocampus and amygdala, and is why people with Alzheimer’s can sometimes develop behaviours that look like those exhibited in KBS and vice versa. This can be dangerous if conditions are misdiagnosed.^{1, 2}

The hippocampus is crucial in learning, memory, and helping us navigate our surroundings. When neurodegeneration in the case of AD or damage in the case of KBS happens here, people can forget recent events and become disoriented in normally familiar places. The amygdala, on the other hand, is crucial in processing emotions and survival instincts that detect danger, strengthening the connections between our emotions and behaviours for example, remembering that touching something hot hurts so as not to do it again.^{1, 2}

When these brain regions break down, the people who suffer from both these conditions may lose their emotional responses or behave in socially inappropriate ways because they no longer remember the fear, embarrassment, or empathy they once knew. Damage to these regions in AD can mimic or produce some KBS-like symptoms, such as excessive eating or other compulsive behaviours, such as hoarding and damage to these regions can cause overlapping symptoms of memory loss and confusion in KBS that are seen in AD.^{1, 2}

Cases of KBS are rare and have not been studied much; however, research has found cases where patients diagnosed with AD also had progressive behavioural symptoms of hyperorality, hypersexuality, and visual agnosia, which are all seen in KBS cases. Researchers also found that out of 178 patients with AD, about 30% exhibited at least 1 key symptom of KBS, suggesting that this might be a result of a form of KBS that is present in those with dementia exhibiting these types of symptoms.⁶

Neuroimaging and neuropathology evidence

Brain scans such as CT,  MRI, and PET scans have shown that both AD and KBS exhibit shrinkage of and damage to the temporal lobes of the brain, especially the hippocampus and the amygdala. Research studies measuring the size of these regions in people with Alzheimer’s found that greater shrinkage is often linked to greater memory loss and more severe emotional and behavioural symptoms.⁷ Doctors also found that there was a correlation between lesions found in the temporal lobes and behaviours such as hyperorality and hypersexuality.⁸ Post-mortem studies of KBS show extensive degeneration to the temporal lobe, in particular the hippocampus and entorhinal cortex, supporting this crossover in symptoms of Alzheimer’s.⁹

Diagnostic considerations and future research

Because KBS affects similar brain regions as AD, especially the amygdala and hippocampus, comparing the two conditions can help us better understand how different types of brain damage can lead to overlapping symptoms. Recognising Klüver-Bucy Syndrome-like symptoms in AD can be challenging, especially since similar behavioural changes such as memory problems, emotional flatness, and compulsion also occur in advanced Alzheimer’s. As well as there being so little research on KBS, these overlaps can make diagnosis for this syndrome tricky, which is why it's important for doctors to carefully examine which brain areas are affected and how the symptoms progress.

Accurately identifying KBS-like features could help predict how a patient’s condition will develop and enable more targeted treatment programs. Both AD and KBS do not have a cure, and cannot be prevented. Treatment options are limited for AD and KBS, and available options aim to improve memory, not emotional and behavioural symptoms.

This has a scope for future research to develop treatments aiming at preserving emotional control by targeting the amygdala and hippocampus.

Summary

AD and KBS are two different types of brain disorders based on causes; however, both are damaged in the same areas of the brain, viz., the hippocampus and amygdala. Therefore, they share similarities in symptoms such as memory loss and emotional and behavioural problems. This overlap in brain areas explains why people with advanced Alzheimer’s can also show KBS-like symptoms such as compulsive behaviours and emotional flatness. While KBS is rare, studying the behavioural symptoms seen in both KBS and AD and understanding their shared features is important to help doctors better understand how symptoms progress and develop new treatments targeting these brain areas.