“The Big Four” dementias – AD, LBD, FTD, and Vascular

There’s a wonderful article in the November/December 2009 issue of Neurology Now magazine.  It features Jerome and Renata Rafferty; Jerome had Lewy Body Dementia and Renata was his caregiver.

The “Other” Dementias (featuring Lewy Body Dementia story)

A companion article is titled “The Big Four.”  It gives short descriptions of four types of dementia – Alzheimer’s, Lewy Body Dementia, Frontotemporal Dementia, and Vascular Dementia.  The article notes that there are over 100 types of dementia.

Below the full text of the article, and a link to it online. You can also download the PDF of the article.


journals.lww.com/neurologynow/Fulltext/2009/05060/The__Other__Dementias.14.aspx –> HTML version

The Big Four
Neurology Now
November/December 2009 – Volume 5 – Issue 6 – p 26-27,31-34

More than 100 types of dementia have been found, but four of them account for nearly 98 percent of all cases of dementia in the United States.


DESCRIPTION: People with AD develop memory problems, often followed by confusion, apathy, depression, emotional volatility, and other problems.

CAUSE: People with AD develop two types of dysfunctional protein in the hippocampus, the part of the brain essential for creating new memories. Tau protein accumulates within neurons in that region, while clumps of amyloid protein develop between neurons in that region. Some researchers, however, suspect that the toxic proteins may be the result of the disease rather than the cause.

TYPICAL CASE: The first symptom of AD almost always involves memory problems, such as forgetting familiar names and misplacing items. As the disease progresses people may have trouble finding their way home or keeping up with routine obligations such as doctor appointments, paying bills, and preparing meals. Later stages may affect the frontal lobes, resulting in erratic emotions, loss of normal inhibition, and hallucinations.

TREATMENT: Since AD results in decreased levels of acetylcholine, a neurotransmitter essential for memory and learning, drugs that boost acetylcholine, such as donepezil and memantine, often help, at least for a while. Other treatments are available for specific symptoms such as depression, hallucinations, and movement disorders, but nothing seems to slow development of the disease.

ON THE HORIZON: Several drugs and vaccines designed to inhibit the production of toxic tau and amyloid protein, or remove it once it appears, are in development. However, people who have tried the drug experimentally failed to improve significantly, even though protein levels declined, sometimes dramatically.


DESCRIPTION: Like Alzheimer’s, LBD produces cognitive decline, but with three additional traits. Instead of declining continuously, people with LBD tend to fluctuate in terms of attention, alertness, ability to speak coherently, and other symptoms. They also tend to have visual hallucinations, often benign. Finally, they tend to develop symptoms of Parkinson’s disease, including rigidity, tremor, and slowness of movement.

CAUSE: A type of protein known as alpha-synuclein clumps into Lewy bodies, which appear inside of cells, or neurons. Lewy bodies may result from the inability of the cell to break down and recycle alpha-synuclein efficiently. As the protein accumulates, it sticks together, as though the cell is trying to gather its own debris to keep it out of the way.

TYPICAL CASE: People with LBD often act out violent dreams that involve being pursued or attacked. They may develop benign hallucinations involving, for example, children or animals running around the house. Attention and concentration may fluctuate, and patients may start to have trouble with visual-spatial abilities-they may misjudge the height of a step or miss a cup when they reach for it. Some people with LBD experience an overwhelming urge to sleep during the day. Their movements also may become rigid and slow, like the symptoms of Parkinson’s disease, and they may develop problems with memory, judgment, and mood, like the symptoms of AD.

TREATMENT: No treatment specifically for LBD exists. However, since LBD affects nearly every neurochemical system in the brain, specific aspects of the disease can be treated. Memory problems can be treated with donepezil and other drugs for AD. Movement disorders may respond to L-dopa and other medications for Parkinson’s disease. Modafinil may alleviate daytime sleepiness.

ON THE HORIZON: No drug yet exists that affects the synuclein protein, although some drugs exist for daytime sleepiness, and another, which resembles methylfenidate, is in development.


DESCRIPTION: FTD includes several disorders that cause the frontal lobes behind the forehead, and the temporal lobes at the sides of the brain, to atrophy and shrink. Patients either develop speech difficulties, known as aphasia, or they display inappropriate social behavior. Aphasia may involve halting, effortful speech with the patient struggling to produce the right word. Behavioral changes may involve indifference to the concerns of others. Some patients developing FTD may start shoplifting or become attracted to shiny objects or fire.

CAUSE: In FTD, a protein known as TDP-43 accumulates within cells at the front of the brain. In one form of FTD known as Pick’s disease, tau protein, found in the hippocampus of people with AD, accumulates within cells in the frontal lobes.

TYPICAL CASE: A person developing FTD generally exhibits personality or mood changes. An outgoing person may become withdrawn and depressed, while an introverted person may become loud and outgoing. Socially inappropriate behavior may also become more common. Later, FTD patients may develop speech difficulties as they lose the ability to recall the meaning of words, or they may start to speak with great fluency while making no sense.

TREATMENT: Only symptomatic treatments are available with medications developed for other disorders, such as psychiatric medications for behavioral problems or mood disorders. There are no treatments for language problems.

ON THE HORIZON: Methylene blue, a drug in development for AD, inhibits the aggregation of tau protein, so it may help patients with Pick’s disease. Another tau aggregation inhibitor known as AL-108, or davunetide, is in clinical trials, and may soon become the first tau-active drug available in the U.S. TDP-43, the offending protein in other forms of FTD, was discovered only three years ago, leaving little time for the development of effective treatments.


DESCRIPTION: Since this dementia results from several small strokes, and strokes can affect any part of the brain, the symptoms of vascular can vary widely. However, they usually include declines in problem-solving ability, memory, and socially appropriate behavior.

CAUSE: Vascular dementia is believed to result from damage to brain cells caused by lack of oxygen when the blood supply is cut during a series of mild strokes. However, one study of 1,000 brains from demented patients who had died found only six that had pure vascular dementia, with the slow progression typical of the disorder. The rest also had another form of dementia.

TYPICAL CASE: To be diagnosed with vascular dementia, a patient must show evidence of a stroke in a location that could affect cognition, and cognitive problems must develop within three to six months of the stroke. A patient who meets these criteria may develop memory problems and have trouble speaking coherently or understanding the speech of others. They may also develop motor difficulties that prevent them from dressing themselves.

TREATMENT: The first goal is to reduce stroke risk by improving cardiovascular health. Statins may be prescribed to lower cholesterol, anti-hypertensives to lower blood pressure, and omega-3 pills to improve triglyceride levels. Low-dose aspirin may be prescribed to inhibit the clotting of the blood, and patients may be urged to give up smoking and drinking and reduce stress.

ON THE HORIZON: Damage from strokes cannot be reversed, but the brain can compensate for some deficits. Physical therapy designed to stimulate brain plasticity may provide some help.

Copyright © 2009, AAN Enterprises, Inc.