3.5.1 Dementia

Summary of Dementia’s

Disorder	Prevalence/Incidence	Clinical Features	Differential Diagnosis
Alzheimer’s disease	50-75% of dementia cases	Memory loss, cognitive impairment, language difficulties, behavioural changes	Vascular dementia, dementia with Lewy bodies, frontotemporal dementia
Vascular dementia	10-20% of dementia cases	Cognitive impairment, gait abnormalities, motor dysfunction	Alzheimer’s disease, dementia with Lewy bodies
Dementia with Lewy bodies	10-25% of dementia cases	Cognitive impairment, parkinsonism, visual hallucinations	Alzheimer’s disease, Parkinson’s disease dementia
Parkinson’s disease dementia	30-40% of patients with Parkinson’s disease	Cognitive impairment in association with motor symptoms	Alzheimer’s disease, vascular dementia, dementia with Lewy bodies
Frontotemporal dementia	5-10% of dementia cases	Changes in behaviour, personality, language	Alzheimer’s disease, vascular dementia, dementia with Lewy bodies

Disorder	Aetiology	Management	Prognosis
Alzheimer’s disease	Abnormal protein deposits, genetic factors, lifestyle factors	Cholinesterase inhibitors, memantine, non-pharmacological interventions	Progressive decline, typically fatal within 8-10 years
Vascular dementia	Stroke, hypertension, atherosclerosis	Control of vascular risk factors, medications to manage symptoms	Progression varies depending on underlying vascular disease
Dementia with Lewy bodies	Accumulation of Lewy bodies in the brain	Cholinesterase inhibitors, dopaminergic agents, non-pharmacological interventions	Progression varies, and may be shorter than Alzheimer’s disease
Parkinson’s disease dementia	Accumulation of Lewy bodies in the brain	Cholinesterase inhibitors, dopaminergic agents, non-pharmacological interventions	Progression varies and may be shorter than Alzheimer’s disease
Frontotemporal dementia	Degeneration of nerve cells in frontal and temporal lobes	Antidepressants, antipsychotics, non-pharmacological interventions	Progression varies depending on the type of frontotemporal dementia

Alzheimer’s Disease

Prevalence/Incidence:

Alzheimer’s disease is the most common cause of dementia, accounting for approximately 60-80% of cases. The prevalence of Alzheimer’s disease increases with age, and it is estimated that 5-8% of people over the age of 65 have Alzheimer’s disease.

Clinical Features:

Alzheimer’s disease is characterized by progressive cognitive decline, including memory loss, impaired judgement and reasoning, and difficulty with language and visual-spatial skills. Patients may also experience behavioural and psychological symptoms, such as agitation, depression, and psychosis.

Differential Diagnosis:

Other causes of dementia, such as vascular dementia, frontotemporal dementia, and dementia with Lewy bodies, must be ruled out. Other medical conditions, such as depression and delirium, can also cause cognitive impairment and must be considered.

Aetiology:

Alzheimer’s disease (AD) is a multifaceted and complex neurodegenerative disorder. While the precise etiology is not completely understood, a combination of genetic, environmental, and lifestyle factors are believed to influence its onset and progression. Here’s an overview:

1. Genetic Factors:
   • Familial Alzheimer’s Disease (FAD): This is a rare form of AD that accounts for less than 1% of cases. It has an early onset, typically affecting individuals before the age of 65. FAD is associated with mutations in specific genes: APP (amyloid precursor protein), PSEN1 (presenilin-1), and PSEN2 (presenilin-2).
   • Late-Onset Alzheimer’s Disease (LOAD): The most common form of AD. One significant genetic risk factor for LOAD is the ε4 allele of the apolipoprotein E (APOE) gene, although having this allele does not mean one will certainly develop AD, nor does its absence guarantee immunity.
2. Biochemical and Pathological Factors:
   • Beta-Amyloid Plaques: One of the hallmark features of AD. These are sticky clumps of protein fragments that accumulate outside neurons, likely disrupting communication between these cells and initiating an inflammatory response leading to widespread neuronal death.
   • Tau Tangles: Inside neurons, tau proteins malfunction and form tangles, which prevent nutrients from traveling within the cells, leading to cell death.
3. Environmental Factors: Some studies suggest that exposure to certain environmental factors, like toxins or viral infections, might be linked to AD. However, more research is needed to elucidate these potential relationships.
4. Lifestyle Factors: There is growing evidence suggesting that factors which increase the risk of cardiovascular disease (like smoking, obesity, diabetes, and hypertension) may also increase the risk of developing AD and other dementias. Additionally, factors like a lack of physical activity, low educational and cognitive engagement, and poor social engagement might also play a role.
5. Vascular Factors: Conditions that damage the heart or blood vessels, including high blood pressure, heart disease, stroke, and diabetes, have been linked to a higher risk of developing AD.
6. Traumatic Brain Injury: There’s a correlation between experiencing a traumatic brain injury and a higher risk of Alzheimer’s later in life.
7. Other Factors: There’s ongoing research exploring the relationship between AD and factors such as chronic inflammation, insulin resistance, and the role of the microbiome in our gut.

It’s important to note that Alzheimer’s disease is a result of a combination of these factors rather than any single cause. Current research in the field of AD is geared towards better understanding these factors, their interplay, and potential interventions to prevent or delay the onset of the disease.

Management:

There is currently no cure for Alzheimer’s disease, and treatment focuses on managing symptoms and improving quality of life. Non-pharmacological interventions, such as cognitive stimulation therapy and physical exercise, may also be beneficial.

The pharmacological management of Alzheimer’s disease primarily involves the use of cholinesterase inhibitors and NMDA receptor antagonists. Cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, work by increasing the levels of acetylcholine in the brain, which is important for cognitive function. Donepezil is typically prescribed at an initial dose of 5 mg once daily, which may be increased to a maintenance dose of 10 mg daily after 4-6 weeks. Rivastigmine is available in oral and transdermal patch forms, with a starting dose of 1.5 mg orally twice daily or a 4.6 mg/24-hour patch, gradually titrating to a maximum of 6 mg twice daily or a 9.5 mg/24-hour patch. Galantamine is started at 4 mg twice daily, with the dose increased every four weeks to a maximum of 12 mg twice daily. For patients with moderate to severe Alzheimer’s disease, the NMDA receptor antagonist memantine may be used. Memantine works by blocking the action of glutamate, a neurotransmitter involved in learning and memory, thus reducing neuronal damage. The initial dose of memantine is 5 mg once daily, gradually titrating to a maximum dose of 20 mg daily over a four-week period. It is important to note that these medications do not cure Alzheimer’s disease but may help slow down the progression of symptoms and improve the quality of life for patients and their caregivers.

Prognosis:

Alzheimer’s disease is a progressive disease, and the prognosis is poor. The average survival time from diagnosis is 4-8 years, although some patients may live for up to 20 years.

Vascular Dementia

Prevalence/Incidence:

Vascular dementia is the second most common cause of dementia, accounting for approximately 10-20% of cases. The prevalence of vascular dementia increases with age, and it is estimated that 1-4% of people over the age of 65 have vascular dementia.

Clinical Features: Vascular dementia is characterized by cognitive impairment that is caused by cerebrovascular diseases, such as stroke or small vessel disease. The clinical features of vascular dementia vary depending on the location and severity of the cerebrovascular disease but typically include memory loss, executive dysfunction, and problems with attention and concentration.

Differential Diagnosis: Other causes of dementia, such as Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies, must be ruled out. Other medical conditions, such as depression and delirium, can also cause cognitive impairment and must be considered.

Aetiology:

Vascular dementia is caused by cerebrovascular diseases, such as stroke or small vessel disease.

Management:

Treatment of vascular dementia focuses on managing underlying cerebrovascular disease and preventing further strokes. Medications such as antiplatelet agents and anticoagulants may be prescribed. Non-pharmacological interventions, such as physical exercise and cognitive stimulation therapy, may also be beneficial.

Prognosis:

The prognosis of vascular dementia varies depending on the location and severity of the cerebrovascular disease, but it is generally poor.

Dementia with Lewy Bodies

Prevalence/Incidence:

Dementia with Lewy bodies accounts for approximately 10-15% of cases of dementia.

Clinical Features:

Dementia with Lewy bodies is characterized by cognitive impairment, parkinsonism, and visual hallucinations. Patients may also experience fluctuations in cognition and mood, as well as sleep disorders and autonomic dysfunction.

Differential Diagnosis:

Other causes of dementia, such as Alzheimer’s disease, vascular dementia, and frontotemporal dementia, must be ruled out. Parkinson’s disease and other parkinsonian disorders must also be considered.

Aetiology:

Dementia with Lewy Bodies (DLB) is the third most common cause of dementia after Alzheimer’s disease and vascular dementia. The etiology of DLB is multifactorial and not completely understood. However, several key elements have been identified:

1. Lewy Bodies:
   • The hallmark feature of DLB is the presence of Lewy bodies, which are abnormal aggregates of the protein alpha-synuclein. These aggregates are found in the brain’s cortex and can interfere with neurotransmitter function.
   • Alpha-synuclein is also involved in Parkinson’s disease, which is why there are overlaps in symptoms and pathology between the two conditions.
2. Neurotransmitter Imbalance:
   • DLB is characterized by reductions in acetylcholine and dopamine, two crucial neurotransmitters. Reduced acetylcholine levels are associated with cognitive decline, while diminished dopamine is linked to the parkinsonian symptoms seen in DLB.
3. Genetic Factors:
   • While most cases of DLB appear sporadic, some familial cases suggest a genetic predisposition. Mutations or variants in certain genes, such as SNCA (which encodes alpha-synuclein) and the glucocerebrosidase (GBA) gene, have been associated with a higher risk of DLB. However, these are not common and do not account for the majority of cases.
4. Overlap with Alzheimer’s and Parkinson’s Pathology:
   • Besides Lewy bodies, individuals with DLB often exhibit some degree of the same pathological changes seen in Alzheimer’s disease, such as beta-amyloid plaques.
   • Additionally, the presence of Lewy bodies, especially in the substantia nigra region of the brain, is a commonality with Parkinson’s disease. This shared pathology helps explain the clinical overlaps between DLB, Alzheimer’s, and Parkinson’s disease.
5. Other Factors:
   • Age: Being over the age of 60 is a significant risk factor for DLB.
   • Gender: Men are more likely than women to develop DLB.
   • Environmental Factors: While not well-established, some suggest that environmental factors, including exposure to certain toxins, might play a role in DLB.
6. Neuroinflammation:
   • Emerging research suggests that neuroinflammation, involving activation of the brain’s immune cells (like microglia), could contribute to the development or progression of DLB.

It’s essential to understand that the aetiology of DLB is complex, with a combination of genetic, biochemical, and possibly environmental factors at play. Many research efforts are underway to better grasp the disease’s mechanisms, which will be pivotal in developing more effective treatments and interventions.

Management:

Treatment of dementia with Lewy bodies focuses on managing symptoms, including cognitive impairment, parkinsonism, and hallucinations. Medications such as cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine) and dopaminergic agents may be prescribed. Non-pharmacological interventions, such as physical exercise and occupational therapy, may also be beneficial.

In addition to cholinesterase inhibitors, the management of DLB may also involve the use of other medications to address specific symptoms. For example, levodopa can be prescribed for Parkinsonism symptoms, such as rigidity and bradykinesia, starting at a dose of 100-200 mg levodopa with a dopa-decarboxylase inhibitor (e.g., 25 mg carbidopa) per day, titrating as needed based on clinical response and tolerability. However, it is crucial to monitor patients for worsening neuropsychiatric symptoms, as levodopa may exacerbate hallucinations or delusions in some individuals.

The use of antipsychotic medications in DLB should be approached with caution, as individuals with DLB can be particularly sensitive to these medications, leading to severe side effects, including worsening of motor symptoms or even neuroleptic malignant syndrome. If antipsychotics are necessary to manage severe neuropsychiatric symptoms, atypical antipsychotics, such as quetiapine, may be used at low doses, starting at 12.5-25 mg per day and increasing cautiously based on clinical response and tolerability. It is essential to work closely with healthcare professionals to develop an individualized treatment plan that addresses the unique needs and symptoms of each patient with dementia with Lewy bodies.

Prognosis:

The prognosis of dementia with Lewy bodies varies depending on the severity of symptoms and response to treatment.

Parkinson’s Disease Dementia

Prevalence/Incidence:

Parkinson’s disease dementia occurs in approximately 30-40% of patients with Parkinson’s disease.

Clinical Features:

Parkinson’s disease dementia is characterized by cognitive impairment that occurs in association with motor symptoms of Parkinson’s disease, such as tremors and rigidity. Patients may also experience visual hallucinations and sleep disturbances.

Differential Diagnosis:

Other causes of dementia, such as Alzheimer’s disease, vascular dementia, and dementia with Lewy bodies, must be ruled out.

Aetiology:

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that primarily affects movement. The exact cause remains elusive, but a combination of genetic, environmental, and molecular factors are believed to contribute to its aetiology. Here’s an overview:

1. Neuropathology:
   • The hallmark feature of PD is the degeneration of dopamine-producing neurons in a region of the brain called the substantia nigra. As these neurons die, dopamine levels in the brain decrease, leading to the movement abnormalities seen in PD.
   • Another distinguishing feature of PD is the presence of Lewy bodies, which are abnormal protein aggregates primarily composed of the protein alpha-synuclein.
2. Genetic Factors:
   • Familial Parkinson’s (which is hereditary and seen in multiple family members) makes up a small percentage of cases. Several genes, including SNCA (which codes for alpha-synuclein), LRRK2, PRKN, PINK1, and DJ-1, have been identified in these families.
   • Sporadic Parkinson’s, which is far more common, isn’t directly inherited, but certain genetic variants can increase the risk. For instance, mutations or variants in the LRRK2 gene are particularly common among certain populations like Ashkenazi Jews and North African Berbers.

Management:

Treatment of Parkinson’s disease dementia focuses on managing both cognitive impairment and motor symptoms. Medications such as cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine) and dopaminergic agents may be prescribed. Non-pharmacological interventions, such as physical exercise and occupational therapy, may also be beneficial.

Prognosis:

The prognosis of Parkinson’s disease dementia varies depending on the severity of symptoms and response to treatment.

Frontotemporal Dementia

Prevalence/Incidence: Frontotemporal dementia accounts for approximately 5-10% of cases of dementia.

Clinical Features:

Frontotemporal dementia is characterized by changes in behaviour, personality, and language. Patients may exhibit disinhibition, apathy, and loss of empathy. Language difficulties may include difficulty with word finding and grammar, as well as a loss of language comprehension.

Differential Diagnosis:

Other causes of dementia, such as Alzheimer’s disease, vascular dementia, and dementia with Lewy bodies, must be ruled out.

Aetiology:

Frontotemporal dementia, is a group of disorders caused by progressive nerve cell loss in the brain’s frontal and temporal lobes. The aetiology of Frontotemporal dementia is complex and multifaceted, involving genetic, molecular, and potentially environmental factors. Here’s an overview:

1. Genetic Factors:
   • Around 30 to 50% of people with Frontotemporal dementia have a family history of the disease, suggesting a strong genetic component.
2. Brain Changes:
   • Over time, the frontal and temporal lobes in Frontotemporal dementia patients visibly atrophy or shrink. This is often detectable through imaging studies, even in the disease’s early stages.
   • The degree and pattern of atrophy can vary based on the Frontotemporal dementia subtype and the underlying genetic or molecular pathology.
3. Other Factors:
   • Age: The onset of Frontotemporal dementia typically occurs between the ages of 40 and 65, but it can start earlier or later. It’s one of the most common causes of dementia in younger adults.
   • Gender: Some studies suggest that men might be slightly more at risk than women, but this is not universally agreed upon.

Management:

Treatment of frontotemporal dementia focuses on managing symptoms, including behaviour and language difficulties. Medications such as antidepressants and antipsychotics may be prescribed but more as symptom management. Non-pharmacological interventions, such as occupational therapy and speech therapy, may also be beneficial.

Prognosis:

The prognosis of frontotemporal dementia varies depending on the severity of symptoms and response to treatment.

Reference:

1. Alzheimer’s Association. (2022). What is Alzheimer’s? Retrieved from https://www.alz.org/alzheimers-dementia/what-is-alzheimers
2. American Heart Association. (2021). Vascular Dementia. Retrieved from https://www.heart.org/en/health-topics/dementia/vascular-dementia
3. Dementia Australia. (2022). Dementia with Lewy bodies. Retrieved from https://www.dementia.org.au/about-dementia/types-of-dementia/dementia-with-lewy-bodies
4. Parkinson Parkinson’s Foundation. (n.d.). Parkinson’s Disease Dementia. Retrieved from https://www.parkinson.org/Understanding-Parkinsons/Parkinsons-Disease-Dementia
5. Mayo Clinic. (2021). Frontotemporal dementia. Retrieved from https://www.mayoclinic.org/diseases-conditions/frontotemporal-dementia/symptoms-causes/syc-20354737
6. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, DC: Author.