Frontotemporal dementia in the context of "Bruce Willis"

Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia is a life-limiting condition, having a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process.

Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most common cause is Alzheimer's disease, a neurodegenerative disorder. Dementia is a neurocognitive disorder with varying degrees of severity (mild to major) and many forms or subtypes. Dementia is an acquired brain syndrome, marked by a decline in cognitive function, and is contrasted with neurodevelopmental disorders. It has also been described as a spectrum of disorders with subtypes of dementia based on which known disorder caused its development, such as Parkinson's disease for Parkinson's disease dementia, Huntington's disease for Huntington's disease dementia, vascular disease for vascular dementia, HIV infection causing HIV dementia, frontotemporal lobar degeneration for frontotemporal dementia, Lewy body disease for dementia with Lewy bodies, and prion diseases. Subtypes of neurodegenerative dementias may also be based on the underlying pathology of misfolded proteins, such as synucleinopathies and tauopathies. The coexistence of more than one type of dementia is known as mixed dementia.

Compulsive buying disorder (CBD) is characterized by an obsession with shopping and buying behavior that causes adverse consequences. It "is experienced as a recurring, compelling and irresistible–uncontrollable urge, in acquiring goods that lack practical utility and very low cost resulting in excessive, expensive and time-consuming retail activity [that is] typically prompted by negative affectivity" and results in "gross social, personal and/or financial difficulties". Most people with CBD meet the criteria for a personality disorder. Compulsive buying can also be found among people with Parkinson's disease or frontotemporal dementia.

Compulsive buying-shopping disorder is classified by the ICD-11 among "other specified impulse control disorders". Several authors have considered compulsive shopping rather as a variety of dependence disorder. The DSM-5 did not include compulsive buying disorder in its chapter concerning substance-related and addictive disorders, since there is "still debate on whether other less recognized forms of impulsive behaviors, such as compulsive buying [...] can be conceptualized as addictions."

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States and Canada—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the broader group of motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and breathe without mechanical support are lost. While only 15% of people with ALS also develop full-blown frontotemporal dementia, an estimated 50% face at least minor changes in thinking and behavior, and a loss of energy, possibly secondary to metabolic dysfunction, is thought to drive a characteristic loss of empathy. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking and/or swallowing). Respiratory onset occurs in approximately 1%–3% of cases.

Most cases of ALS (about 90–95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5–10% of cases have a genetic cause, often linked to a family history of the disease, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.

Tauopathies are a class of heterogeneous neurodegenerative diseases characterized by the neuronal and glial aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. Recent literature has shown that tauopathies can have different clinical and pathological presentations depending on the individual. This rejects the previously held idea that individual tauopathies could be linked to specific diseases.

Lewy bodies are inclusion bodies – abnormal aggregations of protein – that develop inside neurons affected by Parkinson's disease, the Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), and in several other disorders such as multiple system atrophy. The defining proteinaceous component of Lewy bodies is alpha-synuclein (α-synuclein), which aggregates to form Lewy bodies within neuronal cell bodies, and Lewy neurites in neuronal processes (axons or dendrites). In some disorders, alpha-synuclein also forms aggregates in glial cells that are referred to as 'glial cytoplasmic inclusions'; together, diseases involving Lewy bodies, Lewy neurites and glial cytoplasmic inclusions are called 'synucleinopathies'.

Lewy bodies appear as spherical masses in the neuronal cytoplasm that can displace other cellular components such as the nucleus and neuromelanin. A given neuron may contain one or more Lewy bodies. There are two main kinds of Lewy bodies – classical (brainstem-type) and cortical-type. Classical Lewy bodies occur most commonly in pigmented neurons of the brainstem, such as the substantia nigra and locus coeruleus, although they are not restricted to pigmented neurons. They are strongly eosinophilic structures ranging from 8-30 microns in diameter, and when viewed with a light microscope they are seen to consist of a dense core that is often surrounded by a pale shell. Electron microscopic analyses found that the core consists of a compact mass of haphazard filaments and various particles surrounded by a diffuse corona of radiating filaments. In contrast, cortical-type Lewy bodies are smaller, only faintly eosinophilic, and devoid of a surrounding halo with radial filaments. Cortical-type Lewy bodies occur in multiple regions of the cortex and in the amygdala. Cortical Lewy bodies are a distinguishing feature of dementia with Lewy bodies, but they may occasionally be seen in ballooned neurons characteristic of behavioural variant frontotemporal dementia and corticobasal degeneration, as well as in patients with other tauopathies.

Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.

Common proteinopathies that are found in FTLD include the accumulation of tau proteins and TAR DNA-binding protein 43 (TDP-43). Mutations in the C9orf72 gene have been established as a major genetic contribution of FTLD, although defects in the granulin (GRN) and microtubule-associated proteins (MAPs) are also associated with it.