The Key Difference Between FTD and LBD
Lewy Body Dementia is characterized by the accumulation of Lewy bodies and alpha-synuclein in multiple brain regions.
FTD is marked by the degeneration of the frontal and temporal cortices.
Symptoms: Frontotemporal Dementia vs Lewy Body Dementia
To understand the differences between FTD and LBD, let us begin by looking at the symptoms that these diseases cause. As we mentioned previously, LBD causes a range of cognitive and non-cognitive symptoms, while FTD, especially in the early stages, causes symptoms related to behaviour and language.
Cognitive and Non-Cognitive Symptoms: LBD
LBD starts with a range of symptoms that onset slowly and worsen over time, causing detriment to daily activities. The most common symptom of LBD is dementia - an umbrella term refering to a loss of cognitive function. A common symptom of dementia is memory loss, the most frequent initial symptom reported in 53.9% of patients [1], but other symptoms are present.
Reductions in concentration, attention, alertness, and wakefulness are also common in LBD, although this varies from patient to patient. Seeing things that are not there, known as visual hallucinations, is another symptom of LBD, which can be very troubling for individuals.
Problems with movement and posture, including slow movement, difficulty walking, and muscle stiffness, are common motor symptoms in LBD. They are collectively referred to as Parkinsonian motor symptoms.
Cognitive and non-cognitive symptoms progress slowly, so at first, they will not cause any disability. As the disease progresses, patients will have increasing difficulties with movement and thinking, with later stages being characterized by profound disability and inability to care for themselves [2].
Behavioral and Language-Related Symptoms: FTD
FTD is a neurodegenerative disorder that starts with degeneration in the frontal and temporal lobes of the brain. In contrast to LBD, symptoms of FTD can be broadly categorized into two groups: behavioural and language-related symptoms, also known as aphasias.
Behavioural symptoms of FTD include inappropriate actions, apathy, lack of restraint, neglect of personal hygiene and care, compulsive behaviour, and changes in eating habits. These can be difficult to discriminate from psychiatric illnesses and present clinical challenges [3, 4].
Language-related symptoms include difficulty speaking or understanding speech, language recall problems, and loss of reading and writing skills. These language difficulties may consequently result in problems with social interactions [4].
In the beginning of the disease, the affected individual is simply behaving a little unusually. For example, they talk less and seem disinterested in the people around them, and they may occasionally do something "surprising" or inappropriate. However, the symptoms of FTD worsen as the disease progresses, and become more severe in later stages.
It's important to note that the symptoms can vary greatly between patients, depending on the affected areas of the brain.
Prevalence: Frontotemporal Dementia vs Lewy Body Dementia
Prevalence of Lewy Body Dementia
LBD is one of the most common forms of dementia in older populations. The prevalence of LBD varies depending on the population and the diagnostic criteria. In population-based studies, LBD accounted for 3.2-7.1% of all dementia cases, with a higher prevalence of LBD in secondary care settings – settings where patients are in care or nursing homes [5].
In individuals over 70 years of age, the prevalence of LBD is generally higher. In this group, the prevalence in the general population is 5%, whereas in secondary care, the prevalence of LBD symptoms is between 16-20% [6, 7].
However, it's important to note that the actual prevalence of LBD may be higher due to under-diagnosis and misdiagnosis of the condition, as indicated by its overlap with psychiatric symptoms [3, 8, 9].
Prevalence of Frontotemporal Dementia
In contrast to LBD, FTD is a neurodegenerative disorder that is the most common cause of dementia in people under 60 years old [4]. Similarly to LBD, FTD prevalence depends on the population examined. A recent meta-analysis found that the prevalence of FTD among dementia patients over 65 was 2.7%, whereas 12% in dementia patients under 65 years old. The review also identified significant disparities in methodology and diagnostic criteria, where the prevalence in the general population likely ranges from 0.1 to 4.6 cases per 100,000 individuals [10].
Causes: Frontotemporal Dementia vs Lewy Body Dementia
Lewy Body Dementia
LBD is considered a complex condition, most likely caused by the build-up of abnormal deposits of a protein called alpha-synuclein in the temporal lobe and midbrain [1]. These deposits, known as Lewy bodies, disrupt the communication between neurons and neurotransmission using dopamine and acetylcholine. The precise reason why these deposits form is still unknown, although genetics of the alpha-synuclein protein is a prominent risk factor. For example, some people with Parkinson's disease (PD), a condition closely related to LBD, have mutations in the gene that encodes alpha-synuclein, called SNCA. At least 30 mutations associated with PD have been found in the SNCA gene, leading to changes in the structure of alpha-synuclein or excess protein production within cells [11].
Despite this, most instances of PD and, by extension, LBD cannot be traced to a single mutation or genetic profile. This suggests that other factors, such as yet-undiscovered genetic and environmental factors, likely cause LBD [11].
Interestingly and frustratingly, the presence of Lewy bodies alone does not fully explain the cause of LBD. For instance, Lewy bodies are often found in people with Alzheimer's disease and Parkinson's disease, but not everyone with these conditions develops LBD [12].
Frontotemporal Dementia
FTD is also a complex condition with various potential causes which are not fully understood. The causes are genetic factors influencing the structure and function of proteins.
One of the fundamental changes associated with FTD is the loss of nerve cells in the frontal and temporal lobes of the brain. This is often accompanied by an accumulation of atypical forms of two proteins, tau and TDP-43. These proteins occur naturally in the brain, but when they don't work and look as expected, they can damage nerve cells [13].
Recent discoveries have highlighted the role of genetics in causing tau abnormalities, identifying several additional gene changes associated with the condition. In fact, between 20 and 50% of FTD cases are familial, meaning they occur in families with a history of the disease [14]. Of the genes identified, 10 are considered causative, which means they are highly likely to account for protein changes seen in FTD.
However, it's important to note that not all cases of FTD are linked to these known genetic factors. Some cases are sporadic, meaning they occur in individuals without a known family history of the disease.
Pathology: Frontotemporal Dementia vs Lewy Body Dementia
Pathological Characteristics
The pathology of LBD is characterized by Lewy bodies and abnormal aggregates of a protein called alpha-synuclein in multiple brain regions. They can be found in both the brainstem and the cortex. Their presence is essential for a pathological diagnosis of LBD [15]. The formation of Lewy bodies is primarily due to differences in the alpha-synuclein protein's chemical and physical properties, which changes how it interacts with other proteins and makes it prone to accumulation. The accumulation forms the typical fibrils, interfering with axonal transport and synaptic transmission between neurons [16].
FTD pathology, in contrast, is marked by the selective degeneration of the frontal and temporal cortices. The pathology of FTD is termed frontotemporal lobar degeneration (FTLD). It is characterized by a different molecular class of aggregated proteins, the most common being TAR DNA-binding protein-43 (TDP-43), tau, and fused in sarcoma (FUS) [17].
Progression and Distribution
The degeneration of nerve fibre in LBD follows a progressive pattern. Post-mortem studies indicate profound changes to the temporal lobe and midbrain, including regions like the locus coeruleus and hippocampus, the limbic cortex, and the frontal lobe, the brain area responsible for executive function [18].
The presence of Lewy bodies is not the only pathological feature of LBD. Concurrently, many patients also have Alzheimer-type pathology, which includes neurofibrillary tangles and amyloid deposits. Patients would receive a diagnosis of LBD if LBDs are present, although a post-mortem autopsy would be required.
In constrast, FTD begins by damage to the frontal lobe. In particular, the disease often starts with severe scarring of the frontal and temporal cortices and neuronal loss in the upper cortical layers of the frontal lobe. The scarring is caused by astrocytes - glial helper cells in the nervous system. In late disease stages, neuronal loss is evident in deeper layers of the frontal and temporal cortices, as well as the CA1 sector of the hippocampus, corresponding to memory loss [19]. The pathology can extend beyond the frontal and temporal lobes into the hind parts of the brain, which will result in additional symptoms.
