Frontotemporal Dementia And Depression: Understanding The Relationship Between Ftd And Depression

  • Deepti BhardwajM.tech, Industrial Biotechnology, Delhi Technological University (Formerly DCE)

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Introduction

Definition of frontotemporal dementia (FTD)

Frontotemporal dementia (FTD), also known as frontotemporal disorders is an umbrella term that refers to a group of brain diseases. FTD is the result of damage to neurons of the brain located in the frontal and temporal lobes.

The symptoms related to this include emotional and language problems as well as unusual behaviour and personality. FTD is rare and often occurs at a younger age than other forms of dementia. Around 60% of people affected with FTD are between 45 to 64 years.1

Overview of depression

Depression, a common mood disorder also called clinical depression, major depression or major depressive disorder. It is a serious disorder that causes persistent feelings of sadness and loss of interest and impacts a person's feelings, thoughts and daily activities like eating, working and sleeping. It can influence people of every age, gender, race and ethnicity. Women are more prone to be diagnosed with depression than men, but men also get affected by depression.2

Importance of understanding the relationship

In older age, severe depressive symptoms may contribute to the development of neurodegeneration before the manifestation of frontotemporal dementia symptoms. Psychotic depression can be a predictor of FTD.3 The symptoms of FTD like lack of interest, feeling demotivated, lack of energy and low concentration are often misunderstood with depression during early stages resulting in a challenging diagnosis.

It is important to understand that people with these disorders cannot control their behaviours and lack of awareness of their illness increases the rate of misdiagnosis and poor outcomes. Here, we will discuss the types of FTD and its relation to depression.

Frontotemporal dementia (FTD)

FTD reflects progressive symptoms that get worse over time. In its early stages, a person may have one or two symptoms. But as the disease progresses, FTD impacts other parts of the brain and more symptoms start to appear. It is not easy to speculate how long patients with FTD can live. Some patients may live over 10 years after diagnosis, while others may live not more than two years after being diagnosed.

In the early stages, symptoms and order of appearance vary from one person to another resulting in problems to determine the type of FTD a person has. Also, different disorders can show the same symptoms and differ from one stage to another of the disease due to the impact on different parts of the brain. FTD can be categorised as behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and movement disorders.3,4

The types of FTD are discussed below:

Behavioural variant FTD (bvFTD)

It is the most common FTD, which involves changes in behaviour, personality and judgement. Patients affected with this disorder may have difficulty with cognition, but their memory may remain relatively unharmed. The symptoms include:

  • Difficulty in prioritising tasks or activities
  • Problems in planning and management such as the inability to think which steps come first, second or later
  • Repetition of the same activity (tapping feet) or using the same word again and again
  • Impulsively acting/saying/doing unacceptable things without keeping in mind how others recognize the behaviour
  • Loss of filter for what to say, lack of respect, impulsive behaviour or action
  • Showing less interest in family or activities they are interested in or used to care about, lack of motivation and social isolation

Primary progressive aphasia (PPA)

PPA includes changes in the communication ability involving the problem of using language to read, write, speak and understand while having conversation with others. As a result of this, patients may have difficulty related to:

  1. Problem in using or understanding words (aphasia) and difficulty in speaking appropriately (slurred speech)
  2. Patients with PPA may also become mute or unable to speak while reflecting other symptoms
  3. Many people affected with PPA experience symptoms of dementia
  4. Problems related to memory, reasoning, and judgement develop over time
  5. Significant behavioural changes with progress in the disease, similar to those found in bvFTD

PPA, is further categorised based on the type of language problems that appear first. Researchers are unable to fully understand the biological reason for various types of PPA. But they are hopeful to find the link between specific language problems and changes in the brain portion responsible for them.

Movement disorders

When parts of the brain that help to control movement are affected, corticobasal syndrome and progressive supranuclear palsy develop as neurological movement disorders associated with FTD. These disorders may also impact thinking and language abilities of a patient, are mentioned as:

  • Corticobasal syndrome: It is a gradual loss of nerve cells or shrinking in certain parts of the brain and its symptoms begin around age 60. The symptoms include progressive loss of ability to control movement and the prominent symptom can be apraxia, the inability to use the hands to perform a movement like difficulty in closing buttons or operating small appliances despite normal strength
  • Progressive supranuclear palsy: Problems with balance and walking are faced by the patients such as moving slowly, unexplained falls, loss of facial expression, and body stiffness, particularly in the neck and upper body resembling those of Parkinson’s disease. A significant feature of this disorder is problems with eye movements (looking down)

Causes of FTD

The biological and genetic factors are responsible for changes in the brain cells associated with FTD. Scientists describe changes in the pattern of the brain causing FTD by investigating the autopsy after death. Such changes in the brain involve the loss of neurons and abnormal amounts, or forms of proteins called tau and TDP-43.

These proteins are naturally present in the body and aid in the proper cell functioning. But when these proteins work improperly for unknown reasons (reasons not yet fully understood by scientists), neurons of the specific brain part are affected or damaged.

In most of the cases, the causes of an FTD are unknown. Individuals having a family history of FTD are more prone to get affected by such a disorder. Around 10 to 30% of bvFTD is caused by genetics. FTD detected in a family is commonly linked to permanent changes or variations in certain genes.

Genes are the basic unit of heredity which transfers information to the cells about the formation of proteins for the proper functioning of the body's needs. Small changes or alterations in a gene may lead to producing an abnormal protein, which may cause malfunctioning in the brain or disease.1

Several genes are discovered, when mutated can result in FTD:

  • Tau gene (also known as MAPT gene): A small change in this gene leads to malfunctioning in a protein called tau. It forms tangles inside neurons and ultimately causes the deformity of brain cells. Inheritance of a variant in this gene indicates the development of a frontotemporal disorder in such a person, while the exact age of beginning and symptoms cannot be estimated
  • GRN gene: Changes in this gene result in lower production of the protein progranulin, which is essential for the survival of neurons. The disorder in the GRN gene may result in symptoms variations in different family members and the disease can begin at different ages
  • C9ORF72 gene: An unusual change in the gene emerges as the most common genetic deformity in familial frontotemporal disorders

Several other genetic changes leading to rare familial types of FTD have been discovered in recent years. They account for not more than 5% of all cases of FTD. However, families affected by inherited and familial forms of FTD can contribute to advanced research by participating in clinical trials or studies. 

Overview of depression in the context of FTD

Depression can be perceived differently in men and women. While people of all genders may feel depressed and the way to express such symptoms and behaviours used to cope with them may differ. Men are at risk of depression symptoms either undiagnosed or undertreated because they are less likely to realise, discuss and seek help for their emotional problems.2 If someone experiencing some of the following symptoms, nearly every day or for at least 2 weeks, may have depression:

  • Persistent sad or anxious mood
  • Feel hopeless or pessimistic
  • Feeling irritated, frustrated, or restless
  • Feel of helplessness, guilt and worthlessness
  • Lack of interest in hobbies or activities, fatigue and lack of energy
  • Difficulty in concentrating, remembering, or decision-making
  • Difficulty in sleeping or oversleeping and waking up too early in the morning
  • Change in appetite or unplanned changes in weight
  • aches or pains in the body, headaches and digestive problems without a significant cause that is not affected by treatment
  • Thoughts related to death or suicide or suicide attempts

Not every depressed person experiences all such symptoms. Some people may experience only a few symptoms and others may experience many. The associated symptoms of depression overlap with symptoms of FTD like apathy, social isolation, lack of motivation and mood changes that may coexist with depression. The link between the two should be recognised to treat and manage the disorder appropriately.

Relationship between FTD and depression

A clinical study of 72 patients hospitalised in the Medical University of Lodz with final diagnosis, FTD was analysed from 2010-2020. In around 69% of patients concomitant mental disorders were reported, made prior to diagnosis of FTD. Among these patients, 71% disclose depression detection of moderate levels.

The patients diagnosed with psychotic depression first, revealed the longest interval between the emergence of the first psychopathological symptoms (symptoms related to mental illness) and the diagnosis of FTD compared to those with another psychiatric diagnosis (mental disorders).3

Depression as a symptom of FTD: The occurrence of depressive symptoms in patients with FTD is significant. A comparatively high rate of major depression was diagnosed prior to diagnosis of dementia. However, around 50% of patients with bvFTD are misdiagnosed with primary psychiatric disorder due to resemblance with symptoms of depression.

In another analysis of 27 studies, about 33% of patients with FTD (including all subtypes) were found with depressive symptoms. However, the predominance of depressed mood was similar among patients having FTD and other dementias.4

Co-occurrence of FTD and depression: Depression may develop as a psychological response to the diagnosis of FTD. Data analysis of 27 studies indicated that barely 31% of participants had FTD primarily, while 69% had a concomitant diagnosis of a mental disorder. 

Challenges in differentiating FTD from depression

  • In the patients with preexisting depressive symptoms not depending on severity, the diagnosis of FTD took longer time than other patients with various psychiatric illnesses for diagnosis
  • The duration between the appearance of psychopathological symptoms of FTD initially and its diagnosis was longest in patients who were first diagnosed with psychotic depression, compared to those with other psychiatric diagnoses
  • The similarity in behavioural symptoms (lack of interest, feeling demotivated, lack of energy and low concentration) of FTD with depression during early stages results in a challenging diagnosis5
  • Educating patients, families, and healthcare providers about the distinct and overlapping symptoms.
  • Signs or symptoms of depression interrupt day-to-day activities and cause distress to the person encountering them
  • Individuals affected with FTD are relatively young at the onset of the disease which may lower the diagnostic alertness of doctors
  • Planning for the progression of FTD and the potential worsening of depressive symptoms
  • Sustained depressive mood has not been a peculiar trait in patients affected with FTD, but apathy and sometimes mood changes are mostly reported6

In the patients affected with the most severe depression, a steep decline was analysed in their motivation, interpersonal functioning and empathy deficits or apathy. Such depressive symptoms can misinterpret the diagnosis of the degenerative process and may also decrease family awareness about the diagnosis which will be discussed now. 

Diagnostic considerations

Some frontotemporal disorders revealed speech or movement are the primary symptoms, rather than other dementia symptoms. Initially, the type of FTD is diagnosed by physicians and psychologists based on the symptoms as well as the brain scans/imaging and genetic tests of a patient. FTD can be difficult to diagnose due to the similarity of symptoms with other conditions.

For instance, bvFTD is sometimes confused with mood disorders like depression and gets misdiagnosed when a patient has FTD with other types of dementia (Alzheimer's disease). Since these disorders are rare, physicians may become perplexed due to unfamiliarity with the signs or symptoms.1,7

Diagnosis of frontotemporal dementia may require:

  • Examination of symptoms
  • Personal and family medical history
  • Laboratory tests to rule out other conditions
  • Order genetic tests in familial cases
  • Imaging studies of the brain: MRI and PET scans to identify brain atrophy and functional abnormalities specific to FTD
  • Psychiatric evaluation: It examines memory, thinking, physical functioning and language skills and helps to determine whether depression or any other mental health condition is causing FTD
  • Brain autopsy after the death of a person can confirm a diagnosis of FTD
  • Neuropsychological tests to assess cognitive function

Researchers are scrutinising ways for early and accurate diagnosis of FTD to differentiate it from other types of dementia. In an area of research, biomarkers such as proteins or other materials in the blood or cerebrospinal fluid are used to measure the progression of disease and the impacts of treatment.

New methods for further improvement are introduced from time to time for improved brain imaging and neuropsychological testing for better treatment and management of FTD which will be mentioned now.

Treatment and management

Currently, there is no cure for FTD, and no available treatments can slow or stop the disease progression, but there are ways to help manage the symptoms. A team of specialists including doctors, nurses and therapists for speech, physical, and occupational symptoms related with these disorders can help for guiding treatment.1,6

Pharmacological interventions

Medications are available for the treatment of certain behavioural symptoms. Antidepressants (selective serotonin reuptake inhibitors) are frequently prescribed for the treatment. People with symptoms like aggression or delusions may be prescribed low doses of antipsychotic medications by the doctors. 

Psychotherapy and counselling

Lifestyle and supportive interventions

Management of behavioural symptoms involve several approaches and some strategies to consider are:

  • Accept those with behavioural symptoms rather than challenge. Arguing or reasoning with them will not help, as their unusual behaviour or upsetting to others is out of their control. Instead, become sensitive, understand the illness and talk about it
  • When frustrated, take some deep breaths or step out for a few minutes
  • Having open-ended questions becomes difficult to answer like “Where do you want to go today?” rather use specific ones like “Do you want to go to the park or for a walk?”. This is due to the fact that it is easy to choose one out of two
  • Maintain a daily schedule, minimise distractions and redesign the environment to have less confusion and improve sleep of FTD patients
  • In the issue of compulsive eating, one may consider supervising eating or limiting food choices, locking the refrigerator, cabinets and distracting the person with other activities
  • Caregivers may ensure the safety of a patient and family by accepting new responsibilities or arranging care not needed earlier

Behaviour changes associated with FTD can upset, irritate and frustrate family members as well as other caregivers. Understanding of changes in personality, behaviour and knowledge of how to respond minimise frustration and helps to provide the best care to a patient with FTD.

Summary

In FTD, damage to neurons or brain cells is caused by biological and genetic factors. It affects the behavioural, communication and movement of a person, while depression is a common mood disorder.

The distinction between depressive symptoms that are a relatively initial sign of FTD and those not linked to neurodegenerative diseases needs to be understood. The biological pathways and mechanisms linked between frontotemporal dementia and depression are not clearly understood.

The first depressive symptoms occur with significant severity after 60 years of age. The family members of such patients should be aware of the specific behavioural and emotional impacts of FTD. It becomes essential to identify the risk factors for preventing the late diagnosis and effective cure of the disease. 

References

  1. National Institute on Aging [Internet]. 2021 [cited 2024 Aug 25]. What are frontotemporal disorders? Causes, symptoms, and treatment. Available from: https://www.nia.nih.gov/health/frontotemporal-disorders/what-are-frontotemporal-disorders-causes-symptoms-and-treatment
  2. Depression - national institute of mental health(Nimh) [Internet]. [cited 2024 Aug 25]. Available from: https://www.nimh.nih.gov/health/topics/depression
  3. Urban-Kowalczyk M, Kasjaniuk M, Śmigielski J, Kotlicka-Antczak M. Major depression and onset of frontotemporal dementia. Neuropsychiatr Dis Treat [Internet]. 2022 Nov 29 [cited 2024 Aug 25];18:2807–12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719411/
  4. Chakrabarty T, Sepehry AA, Jacova C, Hsiung GYR. The prevalence of depressive symptoms in frontotemporal dementia: a meta-analysis. Dement Geriatr Cogn Disord. 2015;39(5–6):257–71.
  5. Zapata-Restrepo L, Rivas J, Miranda C, Miller BL, Ibanez A, Allen IE, et al. The psychiatric misdiagnosis of behavioural variant frontotemporal dementia in a colombian sample. Front Neurol. 2021;12:729381.
  6. nhs.uk [Internet]. 2017 [cited 2024 Aug 25]. Frontotemporal dementia. Available from: https://www.nhs.uk/conditions/frontotemporal-dementia/
  7. Bott NT, Radke A, Stephens ML, Kramer JH. Frontotemporal dementia: diagnosis, deficits and management. Neurodegener Dis Manag [Internet]. 2014 [cited 2024 Aug 25];4(6):439–54. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824317/

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Deepti Bhardwaj

M.tech, Industrial Biotechnology, Delhi Technological University (Formerly DCE)

I am a healthcare professional, proficient in medical writing and editing with experience in creating and refining high-quality scientific and health-related content. I joined Klarity Health as a healthcare article writer and produced well-researched, detailed, and engaging patient-focused medical articles based on clinical data and scientific literature. My work was focused on ensuring accuracy, clarity, and adherence to ethical and scientific standards, while consistently meeting tight deadlines.

As an editor, I curate and review medical content to uphold the highest standards of quality and consistency. This helps me to enhance the readability of the writer’s work and make an impact on their work, ensuring alignment with editorial guidelines. With a strong academic background in biomedical and biotechnology with a proven track record of managing complex projects, I bring a meticulous approach to my work. My skills in content creation, critical analysis, and quality assurance shaped me to become a valuable contributor to advancing accessible and trustworthy health information. Through my efforts, I continue to bridge the gap between complex medical information and reader-friendly communication.

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