Introduction to Mixed Dementia

Definition: What is mixed dementia?

Dementia is a debilitating condition that leads to a decline in cognitive abilities, memory loss and behavioural changes. About 1 in 10 patients with dementia are diagnosed with mixed dementia. This is when a patient is affected with more than one type of dementia; the most common types are Alzheimer’s disease and vascular dementia, or Lewy body disease. Symptoms are usually more varied and complex as they depend on the relative contributions of each dementia type. Hence, many mixed dementia cases remain undiagnosed.¹

Causes

The exact or definite causes of mixed dementia are relatively hard to underpin as there are overlapping factors that lead to changes in brain function and structure. In the case of Alzheimer’s disease, the condition can be caused by multiple gene variants. It is a polygenic trait. The most common would be a mutation in the apolipoprotein E (APOE) gene responsible for producing a protein that acts as a cholesterol or fat carrier in the blood. People who inherit the ε4 allele are at a higher risk of developing early-onset Alzheimer’s disease as it affects various physiological pathways.² The ε4 allele drives a higher accumulation of amyloid-B (Aβ) plaques in the grey matter of the brain. The protein encoded by this allele differs in 2 amino acids compared to the proteins coded for by the ε2 and ε3 alleles. The ε4 allele also increases the symptom severity of Parkinson’s disease.³ Besides genetic variation, environmental factors and ageing are major risk factors for Alzheimer’s disease development. Smoking, alcohol abuse and underlying health conditions like high blood pressure and depression can contribute to the shrinking of the brain regions and inflammation.² On the other hand, vascular dementia is caused by reduced blood flow to the brain due to stroke or blood vessel blockage. This leads to brain cell death and eventual shrinking of the brain.⁴ Lewy body dementia occurs due to the accumulation of protein clumps in brain cells, interfering with cell signalling. The exact cause of this protein build-up is still unknown.⁵

Common Symptoms of Mixed Dementia

Cognitive Symptoms

Cognitive decline is a major symptom of mixed dementia. The severity will depend on which region of the brain is affected. Mild loss of cognitive function includes memory loss and impaired speech, whereas severe symptoms include inability to move and reliance on others to perform daily tasks.⁶ For instance, as brain cells do not receive sufficient nutrients and oxygen in vascular dementia, patients take a longer time to think and process large amounts of information. Problem-solving may become a challenge for them too.¹ As Alzheimer’s disease progresses, patients will not only have learning difficulties, but they may also become confused about time and place.⁷

Physical Symptoms

In Alzheimer’s disease, plaques may accumulate in regions of the brain that control movement. Those affected may experience poor body coordination. It is harder for them to walk, eat and maintain their balance. Physical problems can occur before or after one has memory loss.⁸ Patients may also have trouble with speech or understanding language as their motor function is impaired. This is seen in Alzheimer’s, Lewy body dementia and vascular dementia.⁹

Emotional and Behavioral Changes

People with mixed dementia can also experience emotional and behavioural changes. For example, patients with Lewy body dementia not only experience visual hallucinations but also mood fluctuations. They may often feel disoriented and confused. Over time, depression or anxiety may become a significant symptom.¹ Patients with mixed dementia, particularly those with vascular dementia, may undergo a personality change. They can be more aggressive or even lose interest in activities they were once passionate about.⁹

Diagnosis of Mixed Dementia

• Initial Assessment:
  • Cognitive tests (e.g., MMSE)
  • Medical history 

To diagnose mixed dementia, cognitive tests like the Mini-Mental State Examination (MMSE) can be conducted to measure cognitive impairment. It contains a series of questions to assess different aspects of cognitive impairment like orientation, language, memory, verbal memory registration, visuospatial abilities and short delayed recall.¹⁰ Mixed dementia can also be diagnosed with one’s medical history. There are 100 risk genes associated with Alzheimer’s disease. For example, those who inherit one copy of the ε4 allele from one or both of their parents are at a higher risk of early-onset Alzheimer’s disease.¹¹ Furthermore, this neurodegenerative condition can also be inherited in an autosomal-dominant pattern, as seen in familial and early-onset Alzheimer’s disease. This is useful in predicting the risk of one inheriting this condition in the future. ¹²

• Imaging and Tests:
  • MRI or CT scans to detect brain changes

Imaging is a conventional method used to diagnose brain conditions, including mixed dementia. In mixed dementia, CT scans (images taken from different angles) should show brain shrinkage, accumulation of brain tumours, or changes in blood vessels. This is an effective way to rule out other conditions that cause similar symptoms to those in dementia. MRI scans are an alternative for diagnosis purposes. For Alzheimer’s disease, clinicians will look out for a shrunken hippocampus as this region is often affected first. Another option is to study a 3D image of the brain by using single-photon emission computerised tomography (SPECT). This is then used to study blood flow patterns which differ in different dementia types.¹³

• Challenges in Diagnosis:

Due to overlapping symptoms of mixed dementia, it can be challenging to diagnose patients. It is difficult to distinguish between different dementia types and to measure changes in brain structure caused by each condition respectively. Nevertheless, the diagnosis of each dementia type is sufficient to administer the appropriate treatment.¹⁴

Treatment and Management Strategies

Medication Management

In Alzheimer’s disease, the accumulation of amyloid-B (Aβ) plaques leads to the death of neurons that use acetylcholine (ACh) as a neurotransmitter. Many medications act as inhibitors of acetylcholinesterase enzyme to increase the concentration of ACh in the synapse and improve nerve cell communication.  Common drugs taken for mild to severe mixed dementia include rivastigmine and Donepezil.¹⁵ Memantine is another common medication that reduces the neurotoxicity in Alzheimer’s; it is an antagonist of the NMDA glutamate receptor. Glutamate is a major excitatory neurotransmitter in the brain. However, excessive levels are found in Alzheimer’s due to the build-up of toxic amyloid-B (Aβ) proteins. This can cause neuronal damage.¹⁶ For vascular dementia, medications usually aim to reduce blood pressure and other underlying conditions like cholesterol and diabetes. Certain medications like low-dose aspirin are taken to reduce the risks of blood clots associated with the health problems mentioned previously.¹⁷

Symptom-Specific Interventions

Symptom-specific interventions are often administered to patients with mixed dementia. Their objective is to alleviate specific symptoms that the patient is experiencing like mood and behavioural changes. For example, antipsychotics or antidepressants like risperidone are taken short-term by patients who are showing continuous aggression, anxiety or distress. Haloperidol is another antidepressant, but there are more severe side effects associated with its intake. Hence, it is often used as a last resort.¹⁸ For patients with mobility issues, physical therapies will be recommended by clinicians. The intensiveness of the activities will depend on the severity of mixed dementia and one’s fitness levels. Lighter exercises include walking up and down the stairs and taking frequent walks. More intense exercises include riding a bike and jogging.¹⁹

Cognitive Support

Clinicians may recommend receiving occupational therapy. Occupational therapy aims to help patients continue their daily tasks by adapting new techniques or utilising equipment. An example would be using memory aids like calendars and labels to manage short-term memory loss.²⁰ Patients are also encouraged to engage in daily activities and games that stimulate cognitive function. This helps patients improve their memory, critical thinking, problem-solving and even language. This slows down the progression of dementia symptoms. Over time, patients’ quality of life can be improved. This also reduces their reliance on their caregivers.⁶

Lifestyle Modifications

To manage mixed dementia symptoms and to reduce the risks of developing dementia, patients are encouraged to live a healthier lifestyle. One should engage in regular physical exercise to improve cardiac health and blood circulation.²¹ Besides, having a healthy diet is essential for maintaining healthy brain function. Mediterranean or DASH diet is recommended as they are high in antioxidants that protect brain cells from damage. This is because they neutralise free radicals that cause oxidative stress to neurons and other brain cells.²²

Caregiver Support and Education

• Role of Caregivers:
  • Daily care and emotional support
  • Monitoring changes in symptoms

Caregivers should be made aware of mixed dementia symptoms to allow detection at an early stage so intervention can be given as early as possible. It should be easier for close family members and friends to identify changes in one’s behaviour, mood and memory abilities. Furthermore, maintaining good relationships with someone with dementia is vital in ensuring their well-being. People with dementia often lose their memories of a person or place and may even feel disoriented at times. Caregivers must offer emotional support to those affected by being understanding of their struggles and encouraging them to join social groups and community activities.²³

• Support Resources:

Providing caregivers with the necessary support resources is equally important. Today, there are various dementia support groups and education programmes for caregivers to learn more about dementia and effective strategies to care for and stay connected with their loved ones who are affected by dementia. There are programmes for effective communication strategies using sign language and financial planning. It is important to raise awareness of dementia and make information as accessible as possible to the public.²⁴

Summary

In summary, mixed dementia patients experience a range of physical, emotional and behavioural symptoms that are often overlapping with different types of dementia. Diagnosing and treating mixed dementia has its challenges. Effective symptom management that focuses on a combination of medication, therapy and lifestyle modifications must be carried out as early as possible. Caregiver support also plays an equally significant role. Overall, a more personalised, integrated and tailored care plan should be given to patients with varying symptoms to ensure an improvement in their quality of life.