Frontotemporal Dementia/Degeneration (FTD)

Frontotemporal degeneration (FTD), also known as frontotemporal dementia, frontotemporal lobar degeneration, originally called “Pick’s disease”, is a rarer form of dementia that may affect between 50,000 and 60,000 people in the United States. There are some differing characteristics of FTD from other forms of dementia. For instance, memory is not usually affected, while FTD does affect behavior, personality, language, and mental and physical functions. Because the average diagnosis age is at approximately 60 years old, it is considered a younger person’s disease rather than an older person’s disease. While this set of disorders is less common than Alzheimer’s in people over the age of 65 years, it is nearly as common as younger-onset Alzheimer’s in people between 45-65 years of age. In about a third of cases, FTD may be an inherited condition. There are no other known risk factors beyond family history and presence of similar disorders.

This type of dementia is associated with a number of different diseases causing degeneration in the frontotemporal regions. Abnormal amounts, or formation of the tau and TDP-43 proteins, cause nerve cell damage in the frontotemporal regions of the brain (the areas behind the forehead and ears). Three subtypes characterize this type of dementia, including behavior variant FTD (bvFTD), primary progressive aphasia (PPA), and disturbances in motor function with or without bvFTD and/or PPA.

bvFTD leads to significant changes in personality and behavior with nerve loss in areas that control conduct, judgment, empathy, foresight, and other capabilities. bvFTD may occur mostly in people 50 to 60 years old. However, this type may develop as early as 20 years of age and later in the 80s.

PPA is divided into two types and with onset typically before the age of 65 years. Semantic variant PPA includes the loss of the ability to understand or formulate words into a sentence. The nonfluent or agrammatic variant of PPA is characterized by hesitant, labored, or ungrammatical speaking.

Treatment is limited to improvement of quality of life as FTD inevitably worsens over time. Medications that reduce agitation, irritability, and depression are typically used to improve quality of life. General accommodation for muscle weakness and coordination issues may include care for wheelchair or bedbound patients in later stages. Muscle weakness can lead to problems in eating, such as chewing and swallowing as well as loss of control over bladder and bowel functions. Typical causes of death in this population are physical changes that cause skin, urinary tract, and/or lung infections.

Limbic-Predominant Age-Related Encephalopathy (LATE)

Researchers have characterized an additional type of non-Alzheimer’s and non-FTD dementia dubbed “LATE” or the limbic-predominant age-related TDP-43 encephalopathy.

This type of dementia is associated with genetic risk factors. At least five genes have been identified that increase risk for this type and other types of dementia. LATE has its own characteristics and may progress more slowly than Alzheimer’s, mostly affecting people over 80 years old. It was estimated that between 15%-20% of patients that have been clinically diagnosed with Alzheimer’s above the age of 80 years may actually be attributable to LATE, possibly making it more prevalent than FTD.

Changes in the brain include brain atrophy and thinning in regions responsible for memory formation. A build-up of the TDP-43 protein in regions that support memory, emotion, behavior and mood lead to related changes. Atherosclerosis is also common in people with LATE. Changes associated with LATE are really only seen on autopsy, so diagnosis is presumptive and usually based on clinical history, MRI or PET findings, and ruling out other causes for dementia. The distinction between types of dementia and possible overlap can complicate efforts to treat people living with dementia.

Additional Causes of Dementia

There are several diseases and conditions that can lead to forms of dementia.

Creutzfeldt-Jakob disease is a group of rare, fatal brain disorders characterized by prion proteins folding into abnormal 3-dimensional shapes, triggering additional folding of prion proteins in the brain. This type of dementia has a rapid onset and destroys brain cells leading to rapid impairment of thinking and reasoning, involuntary muscle movements, and other changes associated with dementia. It significantly shortens life with an estimated death rate of 90% within one year of diagnosis.

Huntington’s disease is a progressive brain disorder with a defective gene component affecting the central area of the brain, causing movement, mood, and thinking skills disorders. Genetic testing can identify the defective gene. Treatment focuses on managing symptoms of involuntary movement, irritability, and obsessive-compulsive thoughts and actions.

Parkinson’s disease dementia is associated with microscopic deposits of the protein alpha-synucelin into Lewy bodies, which are found in dementia with Lewy bodies or DLB. As this protein is lost to the nuclei of brain cells, its function to repair and prevent brain cell death may be reduced, leading to the widespread death of neurons and the resultant dementia changes. Pharmacologic treatment focuses on improving symptoms.

Head trauma that is repeated (chronic) or a concussion from a fall or accident may lead to brain dysfunction. Heavy alcohol use over a long period of time and emotional problems such as stress, anxiety, and depression increase the risk for developing dementia. The cross-over of HIV-infection to the brain can lead to dementia. Delirium, which is a sudden state of confusion and disorientation, may be a symptom of dementia.

Normal pressure hydroencephalus is characterized by excess accumulation of cerebrospinal fluid in the brain’s ventricles can enlarge, and cause damage to nearby brain tissue. This often results in difficulty walking, thinking and reasoning problems, and loss of bladder control. Treatment can sometimes include drainage of excess fluid, which may not correct problems in thinking and loss of bladder control. It is estimated that less than 20% of people with normal pressure hydrocephalus are properly diagnosed and often even misdiagnosed with Alzheimer’s or Parkinson’s disease. Brain imaging can reveal enlarged ventricles without the brain shrinkage that is more common in other forms of dementia.

Other medical conditions, such as tumors, vitamin deficiencies, medication side effects, and problems with thyroid, kidney, or liver can lead to memory problems that may resemble dementia. Long-term alcohol use can lead to dementia symptoms, such as Korsakoff syndrome – a deficiency of the vitamin thiamine, direct toxic effects of alcohol on brain cells, alcohol-related cerebrovascular disease, and biological stress of repeated intoxication and withdrawal. In many of these cases, treatment may halt or resolve dementia symptoms.

There are a number of medications that carry a risk for development of dementia symptoms. These may include anti-depressants, anti-parkinsons, anti-psychotics, medications for overactive bladder, and anti-epileptics.