The Dementias

It’s Not Always Alzheimer’s Disease
Frank LaFerla, Ph.D. and Cordula Dick-Muehlke, Ph.D.

“My mother doesn’t have Alzheimer’s. She just has dementia.” This is often heard when a family member is talking about a loved one who is experiencing memory loss. It may be comforting to use the seemingly safer sounding word, dementia, instead of the dreaded word, Alzheimer’s, to describe troubling behaviors, but it is no longer wise to hide behind words that may hamper appropriate treatment and a proper diagnosis.

Moreover, it may not always be Alzheimer’s disease. There are a number of different disorders that fall under the umbrella term, dementia, just as various cancers (e.g., breast, lung, and colon) fall under the general category of cancer.

Dementia refers to a syndrome that includes memory loss and decline in mental ability severe enough to interfere with activities of daily living. Dementia can result from a variety of irreversible and potentially reversible causes. Reversible causes (5-15%) include depression, vitamin B12 deficiency, hypothyroidism, medication side effects, and infections. It is obviously important determine if one of these reversible and treatable causes is the source of memory and thinking difficulties.

In nearly all cases (85-95%) dementia is due to an irreversible cause. It is important to determine which disorder may be causing a person’s cognitive difficulties, particularly for treatment purposes. Just as cancer medications don’t work for all different forms of cancer, treatments for the different forms of dementia are not effective across the board. For example, medications used to treat Alzheimer’s disease may be ineffective in or actually worsen another type of dementia.

One in 8 individuals over 65 is expected to develop dementia. Currently over 70% of people with dementia never receive a clear diagnosis identifying the cause (e.g., Alzheimer’s disease) of the cognitive impairment. Most older adults receive medical care from primary care and other community physicians who often lack the knowledge necessary to accurately determine the type of dementia affecting an individual.

The most common form of irreversible dementia among the elderly is Alzheimer’s disease, which accounts for approximately 60% of all cases. More than 35 million people in the world have Alzheimer’s disease, including 5.4 million Americans. Alzheimer’s disease adversely impacts California as 600,000 residents are affected, including over 60,000 individuals in Orange County.

In the remaining 40% of cases, dementia is caused by one or a combination of several different disorders. These include Lewy body dementia, frontotemporal dementia, vascular dementia, Parkinson’s disease dementia, Huntington’s disease dementia, Creutzfeldt-Jacob dementia and a number of other very rare disorders.

Mild Cognitive Impairment (MCI) and Alzheimer’s Disease

Senile plaques and neurofibrillary tangles characteristic of Alzheimer’s disease

If you have memory or thinking difficulties that are of concern to you or disrupt your everyday life, it is important that you get an evaluation as soon as possible. Studies show physicians fail to detect cognitive impairment in up to 91% of their patients with mild symptoms and 76% of those with moderate to severe difficulties. Families struggle to get an accurate diagnosis, spending more than two years and seeing more than two doctors in the process. Families often battle over what is “normal” with misinterpretations leading to stress and conflict. The actual diagnosis provides relief for many. An early diagnosis gives families time to plan, to maximize safety, to participate in clinical trials and to experience benefits of the medications that are available today and most effective when started early.

Certain cognitive changes can be expected as part of the normal aging process. For example, new information takes longer to learn, organize, and store. Additionally, we become more susceptible to distraction as we age, and it can take longer to recall information, such as names or words, however the ability to retrieve the information remains intact. Finally, it also becomes harder to quickly switch mental gears between several tasks, that is, “multi-task.”

Cognitive difficulties emerge subtly, such that an individual may notice changes before a physician does. In what is called the “preclinical” stage of Alzheimer’s disease, neuropathological changes (i.e., amyloid plaques and neurofibrillary tangles ) are building up in the brain and the individual may experience symptoms that are concerning. When tested in a doctor’s office using standard cognitive tests, however, the individual still scores in the normal range. Dr. Barry Reisberg referred to this as the stage at which “the patient knows but the doctor doesn’t.”

If cognitive changes progress, the individual may be diagnosed with mild cognitive impairment (MCI). In MCI, the cognitive decline becomes noticeable to others and the affected individual has (1) a measurable impairment in one or more cognitive areas compared to others of the same age, and (2) preserved activities of daily living. While MCI may last for many years and never progress to Alzheimer’s disease, or in some cases revert to normal, multiple studies have shown MCI dramatically increases risk for developing dementia. Notably, 8-15% of people with MCI develop Alzheimer’s disease each year, compared to only 1-2% of cognitively healthy older adults. When MCI progresses to Alzheimer’s disease, the cognitive impairment becomes severe enough to interfere with work, social and everyday functioning.

Individuals with MCI may also experience behavioral and psychological symptoms, such as depression, anxiety, and apathy; these may stem from an awareness of and frustration with the cognitive impairment and/or actual brain changes. Engagement in meaningful activities along with, as necessary, anti-depressants or other medications can help alleviate these symptoms.

Finally, the current FDA-approved medications for Alzheimer’s disease (i.e., Aricept, Razadyne, Exelon, and Namenda) may boost up the individual’s cognitive and everyday functioning but do not ultimately halt progression of the disease.

Lewy Body Dementia

Lewy bodies found in both Dementia with Lewy Bodies and Parkinson’s Disease Dementia

Following Alzheimer’s disease, Lewy Body dementia is the second most common cause of progressive irreversible cognitive impairment. Lewy Body dementia is characterized by abnormal protein deposits called Lewy bodies which appear in nerve cells in the brain stem . These deposits disrupt the brain’s normal functioning, impairing cognition, behavior and motor function, with symptoms such as rigidity and Parkinson’s like tremors. Most cases of Lewy body dementia occur in adults older than 60 and the disorder appears to be more common in men. If you have a family member with Lewy body dementia, you may be at increased risk. Common symptoms include visual hallucinations, fluctuating levels of attention (clear vs. confused days), cognitive and motor dysfunction, sleep behavior disorder and severe sensitivity to antipsychotic drugs.

Symptoms can closely resemble and overlap those of Alzheimer’s and Parkinson’s making Dementia with Lewy Bodies widely under-diagnosed. In fact, some individuals start out with a movement disorder, leading to an initial misdiagnosis of Parkinson’s, then develop dementia and other symptoms of Lewy body dementia. Others present with cognitive dysfunction that may look like Alzheimer’s initially, but with time, hallucinations, motor impairments and fluctuating attention appear. A third smaller group of patients present first with neuropsychiatric symptoms such as hallucinations, behavioral problems or difficulty with complex mental activities and later develop other symptoms.

Drugs that are effective for Lewy body dementia include cholinesterase inhibitors (i.e., Aricept, Razaydne, and Exelon), which increase the level acetylcholine, a chemical messenger important for memory, thought and judgment, and may help with hallucinations. Individuals with Lewy body dementia treated with Parkinson’s disease medications to address motor problems typically become worse, that is, experience increased confusions and hallucinations. Great caution must be taken to ensure that individuals with Lewy body dementia are not given antipsychotic medications, as one third of patients exhibit dangerous sensitivity to neuroleptics.

Frontotemporal Dementia

Pick’s bodies characteristic of frontotemporal dementia

Frontotemporal dementia, which accounts for 6-12% of all cases, causes damage to brain cells in the frontal and temporal lobes. Frontotemporal dementia is the third most common cause of dementia overall, and the second most common cause in persons under age 65. Average age of onset is between 52 and 56, but frontotemporal dementia has been known to start as young as age 22. Frontotemporal dementia has a unique neuropathology, involving the development of Pick’s bodies , rounded, microscopic structures, within neurons in the frontal and anterior temporal lobes.

There are two major variants of frontotemporal dementia: the most common behavioral variant and the less frequent language variant. Within the language variant, changes are characterized as fluent (i.e., semantic dementia) and non-fluent (i.e., progressive non-fluent aphasia). Semantic dementia is characterized by the early loss of knowledge about words, objects, people or facts. While speech is fluent, the content may be rather empty and the individual experiences difficulty with comprehension. In comparison, progressive non-fluent aphasia word meaning and comprehension remain relatively intact, but speech is non-fluent and effortful, with a stuttering quality, frequent omission of words, and mispronunciations.

In the most common behavior form of frontotemporal dementia, memory and spatial abilities are relatively preserved early on, but the individual experiences a host of personality and behavior changes. Common features of frontotemporal dementia include loss of insight and judgment, (e.g., impulsive decisions, poor financial judgments), disinhibition (e.g., socially inappropriate behavior), dietary hyperactivity (e.g., eating more, searching for food, preference for sweets), changes in sexual behavior (e.g., inappropriate advances), stereotyped behaviors (e.g., repetitive speech, movements, or expressions), aspontaneity (e.g., withdrawal, apathy), emotional changes (e.g., emotional bluntness, indifference, excessive emotional reactions), restlessness (e.g., aimless wandering), and speech disturbances (e.g., involuntary automatic repetition of words or phrases said by others).

Antipsychotics and cholinesterase inhibitors are not appropriate for treatment of frontotemporal dementia, although antidepressants such as SSRIs and the medication memantine may be helpful.

Parkinson’s Disease Dementia
Parkinson’s disease is a chronic, progressive neurological condition, and in its advanced stages, the disease can affect cognitive functioning. Over time, many, but not all, people with Parkinson’s disease will develop dementia.

Average age of onset for Parkinson’s is 60, although the disease can first emerge as early as age 26 or as late as age 90. Parkinson’s symptoms include tremors, rigidity, akinsesia (immobility) and postural instability, muscle stiffness and reduced muscular power. While symptoms of Parkinson’s disease dementia are similar to those of Alzheimer’s disease, they occur in a different order. Mental slowing and inflexibility occur early in Parkinson’s disease dementia. People with Parkinson’s disease dementia typically have more difficulty with visual-spatial functioning than those with Alzheimer’s disease. Hallucinations, while common in both disorders, occur early in Parkinson’s disease dementia and late in Alzheimer’s disease.

In the early stages of a dementia, people with Parkinson’s disease can benefit from cues or hints to remember information. Cognitive fluctuations are common, such that the individual may be highly attentive and alert one day but not the next. Episodes of starring, requiring the caregiver to touch or shake the person to “snap out of it,” and daytime sleepiness are common signs of cognitive fluctuations.

Treatment of the Parkinson’s disease itself typically involves use of medications that can increase the level of dopamine, a chemical messenger or neurotransmitter in the brain that is depleted in this disorder. The dementia of Parkinson’s disease can respond well to treatment with the cholinesterase inhibitors (i.e., Aricept, Razadyne, Exelon) used in Alzheimer’s disease. Additionally, as with all dementias, mental, social, and physical stimulation are critical to maintaining the person’s well-being and overall quality of life.

Vascular Dementia
Vascular dementia is caused by poor blood flow to the brain, which deprives brain cells of the nutrients and oxygen they need to function normally. Vascular dementia can result from any number of conditions which narrow the blood vessels, including stroke, diabetes and hypertension. Post-stroke dementia has a sudden onset and a stepwise progression and the cognitive profile is highly variable, depending on the location of the stroke. After a stroke the risk of dementia doubles. Medications for conditions (e.g., hypertension, hyperlipidemia, heart disease, diabetes) that can lead to vascular dementia are vitally important.

Huntington’s Disease
Huntington’s disease is an inherited progressive dementia that affects the individual’s cognition, behavior and movement. Huntington’s disease does not skip generations. Each child of a parent with Huntington’s has a 50/50 chance of inheriting the defective gene. If a child does not inherit the gene, he or she cannot pass it on. If the child does inherit the gene, he or she can pass it on to the next generation.

The cognitive and behavioral symptoms of dementia due to Huntington’s include memory problems, impaired judgment, problems with short-term memory, organizing, coping, concentrating, mood swings, depression and speech problems (especially slurred speech). Delusions and hallucinations may occur. In addition, the individual may experience fidgety behavior, lack of coordination, difficulty ambulating, and uncontrollable jerking movements of the face and body. Symptoms that may also occur include irritability, anxiety, aggressive outbursts and social withdrawal.

The average lifespan after onset is 10-25 years and the younger the age of onset, the more rapid the progression of the disease. Symptoms generally appear between the ages of 30 and 50, but can strike children and young adults.

Discovery of the Huntington’s gene has made possible a predictive test for the disease from a blood sample, allowing those at risk to find out whether or not they will develop this debilitating disorder. Pre-and post-test counseling is critical.

Creutzfeldt-Jacob Disease
Creutzfeldt-Jacob disease is a degenerative neurological disorder also known as “mad cow disease.” Incidence is very low, affecting about one in one million people, or 200 Americans per year. Typical age of onset is 60 and nearly 90% of affected individuals die within year. Incurable, Creutzfeldt-Jacob disease, which results in dementia, is caused by viruses that interfere with the brain’s normal functioning. Dementia due to Creutzfeldt-Jacob disease progresses rapidly and is characterized by memory loss, speech impairment, confusion, muscle stiffness and twitching, and general lack of coordination, making the individual susceptible to falls. Occasionally, blurred vision and hallucinations also occur.

Normal Pressure Hydrocephalus
Normal pressure hydrocephalus involves an accumulation of cerebrospinal fluid in the brain’s cavities. Impaired drainage of this fluid leads to its build-up and results in added pressure on the brain, interfering with the brain’s ability to function normally. Individuals with dementia caused by normal pressure hydrocephalus often experience problems with ambulation, and balance and bladder control, in addition to cognitive impairments involving speech, problem-solving abilities and memory.

Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff syndrome is caused by a deficiency in thiamine (Vitamin B1) and often occurs in alcoholics, although it can also result from malnutrition, cancer which has spread in the body, abnormally high thyroid hormone levels, long-term dialysis and long-term diuretic therapy (used to treat congestive heart failure). Symptoms of dementia caused by Wernicke-Korsakoff syndrome include confusion, permanent gaps in memory, and impaired short-term memory. Hallucinations may also occur.