Differentiating the Irreversible Dementias

Transcription

1 C o n t i n u i n g E d u c a t i o n Differentiating the Irreversible Dementias 1.5 Contact Hour February 2013 CE Expires February 28, 2015 Internal Use Only SouthernCare is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.

2 Introduction Traditionally, dementia has been viewed as a singular, global decline of mental functions. However it is increasingly clear that this is not the case. Different disease processes affect specific parts of the brain, resulting in diverse patterns of mental decline. The location of the disease determines the symptoms that occur. (1) Because Alzheimer's disease (AD) is the most common and most studied cause of dementia, it is often used mistakenly as an umbrella term covering all forms of dementias. In truth, more than 50 conditions can mimic the symptoms of dementia, so it is of utmost importance to get an accurate diagnosis as early as possible. While Alzheimer's disease is, by definition, a type of dementia, a diagnosis of dementia does not always mean that the person with that diagnosis has Alzheimer's disease. Neurons and Neurotransmission Neurons, which are electrically excitable cells in the brain, receive and transmit messages through biochemicals called neurotransmitters. Neurons perform the processing and storage of information involved in brain functioning and facilitate communication between nerve cells. Neurotransmitters (the messengers) cross gaps or synapses, between neurons, and attach to receptors, completing the communication. The synapse is a small gap that physically separates neurons and is the site where neurons communicate with each other. Axon terminals of a neuron sending a message (the pre-synaptic neuron), release neurotransmitters into the synapse. The neurotransmitters diffuse to the other side (the post-synaptic side) where they bind to receptors on the postsynaptic neurons, thereby relaying the message. The Role of Neurotransmitters Substances that act as neurotransmitters can be roughly categorized into three major groups: Amino Acids, Peptides, and Monoamines (norepinephrine, dopamine, Serotonin, acetylcholine). 2

3 The major "workhorse" neurotransmitters of the brain are glutamic acid (glutamate) and GABA. Over half of all brain synapses release glutamate, and 30-40% of all brain synapses release GABA. Since GABA is inhibitory and glutamate is excitatory, both neurotransmitters work together to control many processes, including the brain's overall level of excitation. GABA and glutamate regulate action potential traffic. GABA, an inhibitory neurotransmitter, stops action potentials. Glutamate, an excitatory neurotransmitter, starts action potentials or keeps them going. These signals are relayed to the areas of the brain that control everything from our memories and emotions to our ability to talk, walk, eat, and sleep. Memory is the first to go with AD. The chemicals are responsible for the functions. Neurotransmitter Acetylcholine Dopamine GABA (gammaamino butyric acid) Glutamate Glycine Norepinephrine Serotonin Acetylcholine Role in the Body Used by spinal cord motor neurons to cause muscle contraction and by many neurons in the brain to regulate memory. In most instances, acetylcholine is excitatory. Voluntary movement and emotional arousal. Produces feelings of pleasure when released by the brain reward system. Dopamine has multiple functions depending on where in the brain it acts. It is usually inhibitory. Motor behavior. The major inhibitory neurotransmitter in the brain. It is important in producing sleep, reducing anxiety, and forming memories. The most common excitatory neurotransmitter in the brain. It is important in learning and memory. Used mainly by neurons in the spinal cord. It probably always acts as an inhibitory neurotransmitter. Wakefulness or arousal. Acts as a neurotransmitter and a hormone. In the peripheral nervous system, it is part of the fight-or-flight response. In the brain, it acts as a neurotransmitter regulating blood pressure and calmness. Norepinephrine is usually excitatory, but it is inhibitory in a few brain areas. Memory, emotions, wakefulness, sleep, and temperature regulation. Involved in many functions including mood, appetite, and sensory perception. In the spinal cord, serotonin is inhibitory in pain pathways. Voluntary movement of the muscles, memory 3

4 In the cases of both Alzheimer's and vascular dementia, the neurotransmitters serotonin, norepinephrine and acetylcholine in particular, are dangerously reduced. In the brains of Alzheimer's victims, a number of different kinds of damage can occur within brain cells. Neurofibrillary tangles are bits of protein clogging neurons. Neuritic or senile plaques are debris from dying neurons surrounding protein. As the number of nerve cells and neurotransmitters are reduced, cell communication becomes more and more limited. Vascular dementia can be caused by a number of small strokes, or by blockage in the flow of blood to the brain. (2) Memory Memory can be defined as the registration, retention, and recollection of experiences, thoughts, feelings, sensations, ideas, and knowledge. (3) Memory problems can affect some or all of these processes. Some memory problems develop slowly, while others occur suddenly. Some types of memory problems are reversible, and others result in a gradual, permanent decline in memory. Types of Memory Problems Mild cognitive impairment (MCI) involves memory loss that is more severe than what is considered normal for the aging process. In MCI, there is measurable memory loss, but that loss does not interfere with a patient's everyday life and is not severe enough to be diagnosed as dementia. In many cases, memory loss in people with MCI does worsen, however, and studies suggest that approximately 12 15% of people with MCI eventually develop Alzheimer's disease. Mild cognitive impairment can also affect a person's language ability, judgment, and reasoning. Dementia is a condition that causes memory loss that interferes with a person s ability to perform everyday tasks. In dementia, memory becomes impaired, along with other cognitive skills, such as language use, judgment, and awareness. The most common type of dementia is Alzheimer's disease. Other forms include frontotemporal dementia (sometimes called Pick's disease), Lewy Body dementia, vascular dementia, and mixed dementia. The Dementias Dementia is a clinical state characterized by loss of function in multiple cognitive domains. The most commonly used criteria for diagnoses of dementia is the DSM-IV (Diagnostic and Statistical Manual for Mental Disorders, American Psychiatric Association). Diagnostic features includes: memory impairment and at least one of the following: aphasia, apraxia, agnosia, disturbances in executive functioning. In addition, the cognitive impairments must be severe enough to cause impairment in social and occupational functioning. Importantly, the decline must represent a decline from a previously higher level of functioning. Finally, the diagnosis of dementia should NOT be made if the cognitive deficits occur exclusively during the course of a delirium. 4

5 To be classified as a type of dementia, a disorder must meet the following two criteria: Criteria 1: it must cause decline in at least two of the following four essential cognitive functions: Memory Ability to generate coherent speech or understand spoken or written language Capacity to plan, make sound judgments, and carry out complex tasks Ability to process and interpret visual information Criteria 2: the decline must be severe enough to interfere with day-to-day life. Different Types of Dementia Dementias are historically associated with distinct symptom patterns and distinguishing microscopic brain abnormalities. Increasing evidence from long-term epidemiological observation and autopsy studies suggests these distinctions are somewhat artificial and lead researchers to believe that symptoms and pathologies frequently overlap and can be further complicated by co-existing health conditions. The irreversible types of dementia include: Vascular Dementia Mixed Dementia Lewy Body Dementia Parkinson s Disease Dementia Frontotemporal Dementia A Snapshot Comparison to Alzheimer s Disease (4) Vascular dementia/vascular cognitive impairment Dementia with Lewy bodies and Parkinson s disease with dementia Frontal variant of fronto-temporal lobar degeneration (fronto-temporal dementia) For temporal variants of frontotemporal lobar degenerations, Characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Defective processing of visual information, better performance on executively supported verbal learning tasks, greater attention variability, poorer qualitative executive functioning, and presence of moodcongruent visual hallucinations Better retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. Progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic 5

6 Vascular (Multi-Infarct) Dementia Vascular dementia is the second most common cause of dementia, after Alzheimer's disease. It accounts for up to 20 % of all dementias and is caused by brain damage from cerebrovascular or cardiovascular problems - usually strokes. It also may result from genetic diseases, endocarditis (infection of a heart valve), or amyloid angiopathy (a process in which amyloid protein builds up in the brain's blood vessels, sometimes causing hemorrhagic or "bleeding" strokes). In many cases, it may coexist with Alzheimer's disease. Unlike people with Alzheimer's disease, people with vascular dementia often maintain their personality and normal levels of emotional responsiveness until the later stages of the disease. People with vascular dementia frequently wander at night and often have other problems commonly found in people who have had a stroke, including depression and incontinence. While Alzheimer's is a very slow gradual process over time, usually manifesting as deficits in short-term memory and executive function, vascular dementia is usually a step-wise decline involving various areas of the brain unequally. Many cases can be mixed, having both elements of cerebrovascular disease and the plaque/tangle pathology of Alzheimer's. In vascular dementia, changes in thinking skills sometimes occur suddenly following strokes that block major brain blood vessels. Thinking problems also may begin as mild changes that worsen gradually as a result of multiple minor strokes or other conditions that affect smaller blood vessels, leading to cumulative damage. A growing number of experts prefer the term "vascular cognitive impairment (VCI)" to "vascular dementia" because they feel it better expresses the concept that vascular thinking changes can range from mild to severe. (5) On the other hand, Alzheimer's is progressive, starting in the hippocampus and progressing to other areas of the brain ultimately impairing respiratory and cardiac functions. Short term memory goes first, followed by language functions, long term memory, executive functions, etc. Vascular cognitive impairment is not a single disease but rather it is a group of syndromes relating to different vascular mechanisms. Vascular dementia is preventable thereby making early detection and an accurate diagnosis important. People who develop vascular dementia may have a history of heart attacks. High blood pressure, high cholesterol, diabetes, or other risk factors for heart disease are often present. Patients who have had a stroke are at increased risk for vascular dementia. Recently, vascular lesions have been thought to play a role in AD. Sub-Types Many subtypes of vascular dementia have been described. The spectrum includes ranges from mild vascular cognitive impairment to mixed dementia (combination of AD and vascular dementia). Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. Mild vascular cognitive impairment can occur in elderly persons. It is associated with cognitive decline that is worse than expected for age and educational level, but the effects do not meet the criteria for dementia and are not associated with vascular risk factors or evidence of silent strokes or extensive white matter infarcts on CT scanning. These people have subjective and objective evidence of memory problems, but their daily functional living skills are within normal limits. 6

7 Symptoms Vascular dementia is a progressive disease, worsening over time. Symptoms can vary widely, depending on the severity of the blood vessel damage and the part of the brain affected. Memory loss may or may not be a significant symptom depending on the specific brain areas where blood flow is reduced. Vascular dementia symptoms may be most obvious when they happen soon after a major stroke. Symptoms of vascular dementia may appear suddenly and then remain stable. Sudden post-stroke changes in thinking and perception may include: Confusion Disorientation Trouble speaking or understanding speech Vision loss These changes may happen at the same time as more familiar physical stroke symptoms, such as a sudden headache, difficulty walking, or numbness or paralysis on one side of the face or the body. Other vascular dementia symptoms include: Trouble paying attention and concentrating Reduced ability to organize thoughts or actions Decline in ability to analyze a situation, develop an effective plan, and communicate plan to others Difficulty deciding what to do next Problems with memory (Forgetfulness may or may not be present) Restlessness and agitation Unsteady gait Sudden or frequent urge to urinate, or inability to control passing urine Wandering at night Depression Common early signs of widespread small vessel disease include impaired planning and judgment; uncontrolled laughing and crying; declining ability to pay attention; impaired function in social situations; and difficulty finding the right words. Diagnosis Because vascular cognitive impairment may often go unrecognized, many experts recommend professional screening with brief tests to assess memory, thinking and reasoning for everyone considered to be at high risk for this disorder. Individuals at highest risk include those who have had a stroke or a transient ischemic attack (TIA, also known as a "ministroke"). Additional high-risk groups include those with high blood pressure, high cholesterol, or other risk factors for heart or blood vessel disease. (5) Professional screening for depression is also recommended for high-risk groups. Depression commonly coexists with brain vascular disease and can contribute to cognitive symptoms. If brief screening tests suggest changes in thinking or reasoning, a more detailed assessment is needed. Core elements of a workup for vascular dementia typically include: 7

8 A thorough medical history, including family history of dementia Evaluation of independent function and daily activities Input from a family member or trusted friend In-office neurological examination assessing function of nerves and reflexes, movement, coordination, balance and senses Laboratory tests including blood tests and brain imaging (5) According to a 2011 scientific statement issued by the American Heart Association (AHA) and the American Stroke Association (ASA), also endorsed by the Alzheimer's Association and American Academy of Neurology (AAN), the following three criteria suggest the greatest likelihood that mild cognitive impairment (MCI) or dementia is caused by vascular changes: 1. The diagnosis of dementia or mild cognitive impairment is confirmed by neuro-cognitive testing, which involves several hours of written or computerized tests that provide detailed evaluation of specific thinking skills such as judgment, planning, problem-solving, reasoning and memory. 2. There is brain imaging evidence, usually with magnetic resonance imaging (MRI), showing evidence of either: A. A recent stroke, or B. Other brain blood vessel changes whose severity and pattern of affected tissue are consistent with the types of impairment documented in neuro-cognitive testing. There is no evidence that factors other than vascular changes are contributing to cognitive decline. (5) Causes and Risks As with Alzheimer's disease, advancing age is a major risk factor for vascular cognitive impairment or dementia. Additional risk factors are the same ones that raise risk for heart problems, stroke, and other diseases that affect blood vessels. Many of these vascular factors also raise risk for Alzheimer's. (5) Mixed Dementia Mixed dementia is a condition in which abnormalities characteristic of more than one type of dementia occur simultaneously. In the most common form of mixed dementia, the abnormal protein deposits associated with Alzheimer's disease coexist with blood vessel problems linked to vascular dementia. Alzheimer's brain changes also often coexist with Lewy bodies. In some cases, a person may have brain changes linked to all three conditions: Alzheimer s Disease, vascular dementia, and dementia with Lewy bodies. (6) Some experts recommend suspecting mixed dementia whenever a person has both the hallmark abnormalities of Alzheimer s and another type of dementia, most commonly vascular dementia. Symptoms Mixed dementia symptoms may vary, depending on the types of brain changes involved and the brain regions affected. In many cases, symptoms may be similar to or even indistinguishable from those of Alzheimer's or another type of dementia. In other cases, a person's symptoms may suggest that more than one type of dementia is present. (6) 8

9 Lewy Body Dementia Dementia with Lewy bodies (DLB) is a type of progressive dementia that leads to a decline in thinking, reasoning and independent function because of abnormal microscopic deposits that damage brain cells over time. Lewy bodies are found throughout the outer layer of the brain (the cerebral cortex) and deep inside the midbrain and brainstem. Most experts estimate that dementia with Lewy bodies is the third most common cause of dementia after Alzheimer s disease and vascular dementia, accounting for 10 to 25 percent of cases. LBD is an umbrella term for two related clinical diagnoses, dementia with Lewy bodies and Parkinson's disease dementia. Lewy bodies are also found in other brain disorders, including Alzheimer s disease and Parkinson s disease dementia. Many people with Parkinson's eventually develop problems with thinking and reasoning, and many people with DLB experience movement symptoms, such as hunched posture, rigid muscles, a shuffling walk and trouble initiating movement. (5) This overlap in symptoms and other evidence suggest that DLB, Parkinson's disease and Parkinson's disease dementia may be linked to the same underlying abnormalities in how the brain processes the protein alpha-synuclein. Alpha-synuclein (also α- synuclein) is a protein whose function in the healthy brain is currently unknown. It is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies, protein clumps that are the pathological hallmark of Parkinson s disease. Many people with both DLB and Parkinson's dementia also have plaques and tangles, which are the hallmark brain changes linked to Alzheimer's disease. (5) Key Differences Between Alzheimer s and DLB Memory loss tends to be a more prominent symptom in early Alzheimer's than in early DLB, although advanced DLB may cause memory problems in addition to its more typical effects on judgment, planning and visual perception. Movement symptoms are more likely to be an important cause of disability early in DLB than in Alzheimer's, although Alzheimer's can cause problems with walking, balance and getting around as it progresses to moderate and severe stages. Hallucinations, delusions, and misidentification of familiar people are significantly more frequent in early-stage DLB than in Alzheimer's. REM sleep disorder is more common in early DLB than in Alzheimer's. Disruption of the autonomic nervous system, causing a blood pressure drop on standing, dizziness, falls and urinary incontinence, is much more common in early DLB than in Alzheimer's. (5) Three significant changes or pathological features are seen in brains afflicted by DLB: The brain's cerebral cortex (outer layers of the brain) degenerates or shrinks. This can affect reasoning and complex thinking, understanding personality, movement, speech and language, sensory input and visual perceptions of space. Degeneration also occurs in the limbic cortex at the center of the brain, which plays a major role in emotions and 9

10 behavior. Lewy bodies form throughout these degenerating cortical areas. Nerve cells die in the midbrain, especially in an area that also degenerates in Parkinson's disease, the substantia nigra, located in the brainstem. These cells are involved in making the neurotransmitter (brain messenger) dopamine. Lewy bodies are found in the nerve cells that remain. The midbrain is involved in memory formation and learning, attention, and psychomotor (muscular movement) skills. Lesions called Lewy neuritis that affect nerve cell function are found in DLB brains, especially in the hippocampus, an area of the brain essential for forming new memories. (7) Symptoms Changes in thinking and reasoning Confusion and alertness that varies significantly from one time of day to another or from one day to the next Parkinson's symptoms, such as a hunched posture, balance problems and rigid muscles Visual hallucinations Delusions Trouble interpreting visual information Acting out dreams, sometimes violently, a problem known as rapid eye movement (REM) sleep disorder Malfunctions of the "automatic" (autonomic) nervous system Memory loss that may be significant but less prominent than in Alzheimer's (5) Diagnosis A diagnosis of Parkinson's' disease dementia (PDD) requires a well established diagnosis of Parkinson's disease that later progresses into dementia, along with very similar features to DLB. A rather arbitrary time cutoff was established to differentiate between DLB and PDD. People whose dementia occurs before or within 1 year of Parkinson's symptoms are diagnosed with DLB. People who have an existing diagnosis of Parkinson's for more than a year and later develop dementia are diagnosed with PDD. (8) As with other types of dementia there is no single test that can conclusively diagnose dementia with Lewy bodies. Today, DLB is a "clinical" diagnosis, which means it represents a doctor's best professional judgment about the reason for a person's symptoms. The only way to conclusively diagnose DLB is through a postmortem autopsy. A central feature of LBD is progressive dementia, with deficits in attention and executive function being typical. However, prominent memory impairment may not be evident in the early stages. Other core features include fluctuating cognition with pronounced variations in attention and alertness, recurrent complex visual hallucinations, typically well formed and detailed and spontaneous features of Parkinsonism. (8) A clinical diagnosis of LBD can be probable or possible based on different symptom combinations. 10

11 A probable LBD diagnosis requires either: Dementia plus two or more core features, or Dementia plus one core feature and one or more suggestive features. A possible LBD diagnosis requires: Dementia plus one core feature, or The diagnosis is DLB when: Dementia symptoms consistent with DLB develop first When both dementia symptoms and movement symptoms are present at the time of diagnosis When movement symptoms develop within a year after DLB diagnosis. (5) The diagnosis is Parkinson s disease dementia when a person is originally diagnosed with Parkinson's based on movement symptoms, and dementia symptoms don't appear until a year or more later. (5) Must be present: Progressive cognitive decline (decrease in thinking ability) that interferes with normal social or occupational activities. Memory problems do not necessarily occur in the early period but will occur as DLB progresses. Attention, language, understanding and reasoning, ability to do arithmetic, logical thinking and perceptions of space and time will be impaired. (7) Two of the following are present (one also indicates possibility of DLB): Fluctuating cognition and mental problems vary during the day, especially attention and alertness. Visual hallucinations, detailed and well-formed visions occur and recur. Parkinsonism: motor related and movement problems appear. (7) A DLB diagnosis is even more likely if the patient also experiences repeated falls, fainting, brief loss of consciousness, delusions, or is sensitive to neuroleptic medications that are given to control hallucinations and other psychiatric symptoms. Finally, the timing of symptoms is a reliable clue: if both mental and motor symptoms appear within one year of each other, DLB is more likely the cause. Signs of stroke or vascular dementia usually negate the likelihood of DLB. (7) Symptoms Parkinson's disease dementia is a decline in thinking and reasoning that develops in someone diagnosed with Parkinson's disease at least a year earlier. Common symptoms include: Changes in memory, concentration and judgement Trouble interpreting visual information Muffled speech Visual hallucinations Delusions, especially paranoid ideas 11

12 Depression Irritability and anxiety Sleep disturbances, including excessive daytime drowsiness and rapid eye movement (REM) sleep disorder (5) Diagnosis As with other types of dementia there is no single test or any combination of tests that conclusively determines that a person has Parkinson's disease dementia. Many experts now believe that Parkinson's disease dementia and dementia with Lewy bodies are two different expressions of the same underlying problems with brain processing of the protein alphasynuclein. But most experts recommend continuing to diagnose dementia with Lewy bodies and Parkinson's dementia as separate disorders. (5) Guidelines for diagnosing Parkinson's disease dementia and dementia with Lewy bodies are: The diagnosis is Parkinson's disease dementia when a person is originally diagnosed with Parkinson's based on movement symptoms and dementia symptoms don't appear until a year or more later. The diagnosis is Dementia with Lewy Bodies when: Dementia symptoms consistent with dementia with Lewy bodies develop first When both dementia symptoms and movement symptoms are present at the time of diagnosis When movement symptoms develop within a year of a dementia with Lewy bodies diagnosis (5) Causes and Outcomes Certain factors at the time of Parkinson's diagnosis may increase future dementia risk, including older age, greater severity of motor symptoms, and having mild cognitive impairment (MCI). There are no treatments to slow or stop the brain cell damage caused by Parkinson's disease dementia. Current strategies focus on helping symptoms. Like other types of dementia that destroy brain cells, Parkinson's disease and Parkinson's disease dementia get worse over time and speed of progression can vary. About Fronto-Temporal Dementia Fronto-temporal dementia (FTD) is a neurodegenerative disease of unknown etiology, with atrophy and neuronal loss in the frontal and temporal lobes of the brain resulting in a gradual and progressive decline in behavior or language. Common pathologic findings in FTD are atrophy and neuronal loss affecting the frontal and temporal lobes of the brain. The cell damage caused by frontotemporal dementia leads to tissue shrinkage and reduced function in the brain's frontal and temporal lobes, which control planning and judgment; emotions, speaking and understanding speech; and certain types of movement. Below is the brain of a patient with frontotemporal dementia showing atrophy of the frontal and anterior temporal lobes. Frontotemporal Dementia 12

13 FTD includes a range of specific disorders with different core symptoms. But there's significant symptom overlap, especially as these disorders progress. The disorders grouped under FTD fall into three broad categories. Scientists have identified a range of microscopic brain abnormalities implicated in FTD. The overall term for the brain cell damage and tissue shrinkage associated with FTD is fronto-temporal lobar degeneration. (5) FTD used to be called Pick's disease. Other terms used to describe FTD include fronto-temporal disorders, fronto-temporal degeneration and frontal lobe disorders. FTD was once considered rare, but it's now thought to account for up to 10 to 15 percent of all dementia cases. It's still believed to be less common than Alzheimer s Disease, vascular dementia and Lewy body dementia. FTD tends to occur at a younger age. In those younger than age 65, FTD may account for up to 20 to 50 percent of dementia cases. People usually develop FTD in their 50s or early 60s, making the disorder relatively more common in this younger age group. (5) The person usually has a family history of ALS, psychiatric disease, depression, or alcoholism (~ 40 % familial). Brain imaging may help in diagnosis. Symptoms As you can see on the diagram, fronto-temporal dementia and semantic dementia affect areas towards the front of the brain, whereas Alzheimer s disease affects the areas at the back. The different disease processes are therefore associated with different symptoms. Experts group fronto-temporal dementia into three main categories. Initially, these groups tend to cause different core symptoms based on the first parts of the brain's frontal or temporal lobes they affect. But there's increasing overlap in symptoms as these disorders progress. Symptoms related to the three types of FTD include: Behavioral variant fronto-temporal dementia (bvftd) takes its greatest toll on personality and behavior. It may begin with subtle changes that may be mistaken for depression. As FTD progresses, people often develop lack of inhibition, a striking loss of restraint in personal relations and social life. (5) Primary progressive aphasia (PPA) affects language skills in early stages, but often also affects behavior as it advances. The two chief forms of PPA have somewhat different symptoms: In semantic dementia, people speak easily, but their words convey less and less meaning. They tend to use broad general terms, such as "animal" when they mean "cat." Language comprehension also declines. In progressive non-fluent aphasia, people lose their ability to generate words easily, and their speech becomes halting, "tongue-tied" and ungrammatical. Ability to read and write also may be impaired. (5) FTD movement disorders affect certain involuntary, automatic muscle functions. These disorders also may impair language and behavior. The two primary FTD movement disorders are: Corticobasal degeneration (CBD), which causes shakiness, lack of coordination, and muscle rigidity and spasms. Progressive supranuclear palsy (PSP), which causes walking and balance problems, frequent falls and muscle stiffness, especially in the neck and upper body. It also affects eye movements. (5) 13

14 Diagnosis There is no single test or any combination of tests that can conclusively diagnose fronto-temporal dementia. FTD is a "clinical" diagnosis representing a doctor's best professional judgment about the reason for a person's symptoms. Magnetic resonance imaging (MRI) often plays a key role in diagnosis because it can detect shrinkage in the brain's frontal and temporal lobes, which is a hallmark of FTD. (5) Key Differences between FTD and Alzheimer s Because Alzheimer s disease affects the areas at the back of the brain, patients with Alzheimer s disease typically have problems in memory, visual and spatial function, and language. They find it difficult to learn new information, see things around them, and retrieve words in conversation. In contrast to their often debilitating mental decline, they are fully insightful and concerned about their problems, with preserved personality and behavior. (1) Patients with fronto-temporal dementia and semantic dementia are entirely different. Since the posterior areas of the brain remain unaffected, there are no problems in visual function. However, the affected frontal areas are responsible for controlling behavior, meaning that there are often profound changes in personality. While problems with serotonin and dopamine signal-transmission are well known, the cholinergic system does not seem to be affected. (1) In some cases, it may be hard to distinguish FTD from Alzheimer's disease. In the future, tests to detect specific protein abnormalities linked to Alzheimer's and FTD may help clarify the diagnosis in difficult cases. Age at diagnosis may be an important clue. Most people with FTD are diagnosed in their 50s and early 60s. Only about 10 percent are diagnosed after age 70. Alzheimer's, on the other hand, grows more common with increasing age. Memory loss tends to be a more prominent symptom in early Alzheimer's than in early FTD, although advanced FTD often causes memory loss in addition to its more characteristic effects on behavior and language. Behavior changes are often the first noticeable symptoms in bvftd, the most common form of FTD. Behavior changes are also common as Alzheimer's progresses, but they tend to occur later in the disease. Problems with spatial orientation for example, getting lost in familiar places are more common in Alzheimer's than in FTD. Problems with speech. Although people with AD may have trouble thinking of the right word or remembering names, they tend to have less difficulty making sense when they speak, understanding the speech of others, or reading than those with FTD. (5) Hallucinations and delusions are relatively common as Alzheimer's progresses, but relatively uncommon in FTD. Causes and Risks Researchers have identified abnormal deposits of several proteins inside the brain cells of those who died with fronto-temporal dementia. Scientists have not yet learned what causes these protein abnormalities or solved the mystery of why the damage associated with FTD targets the brain's frontal and temporal lobes. The only known risk factor for FTD is a family history of the disease. 14

15 Treatment and Outcomes Current fronto-temporal dementia treatment focuses on managing symptoms, primarily those affecting behavior. Emerging insights into specific protein abnormalities associated with FTD may identify targets for new treatments aimed at underlying disease processes. (5) FTD inevitably gets worse, usually over several years. In advanced FTD, people typically become mute and bedbound. Like other types of dementia FTD shortens lifespan. Studies suggest that most people with FTD survive an average of six to eight years, but survival can range from two to 20 years. Semantic Dementia Semantic dementia (SD) is another clinical manifestation of frontotemporal lobar degeneration, associated with shrinkage of the temporal lobes. SD is a relatively rare disorder and is much less common than FTD. However, like FTD, people with SD tend to be affected at a relatively young age, generally between the ages of 50 and 65. Relatives report a history of a similar disorder in the family in about a quarter of cases. (1) Symptoms In SD, people progressively lose their ability to remember the meaning of words, objects and faces. Changes may also occur in people s behavior, although these are qualitatively different from those observed in FTD. Sufferers are generally fit and physically healthy although they may become slowed down in the later stages of the disease. Pick s Disease Pick s Disease is one type of FTD and progresses more quickly than Alzheimer s. A progressive dementia defined by clinical and pathologic criteria. Unlike Alzheimer s disease and other dementias that present with cognitive deficits localized to the posterior (parietal) cortex, Pick s disease typically affects the frontal and/or temporal lobes. The disorder is progressive and invariably leads to increasing disability. The disease runs a shorter course than Alzheimer s disease, on average about 6 years. Pick's Disease symptoms are often hard to distinguish from Alzheimer's Disease. Pick's Disease damages nerve cells in the brain's frontal and temporal lobes. Nerve cells affected by Pick's Disease weaken and eventually die. A sudden personality change is the main symptom of Pick's Disease, usually coupled with changes in social behavior. The first symptoms are changes in personality, judgment, planning, and social skills. Individuals may make rude or off-color remarks to family or strangers or make unwise decisions about finances or personal matters. They may show feelings disconnected from the situation, such as indifference or excessive excitement. They may have an unusually strong urge to eat and will gain weight as a 15

16 result. In some individuals whose main symptoms are a disturbance of speech and language (primary progressive aphasia), the clinical course can be slow. The patient's ability to function at home may be spared for 10 or more years post-onset. Creutzfeldt-Jakob Disease Creutzfeldt-Jakob Disease is a spongiform disease, meaning that the brain resembles a sponge. Creutzfeldt-Jakob Disease was identified as the human disorder believed to be caused by eating meat from cattle affected by mad cow disease. CJD is a rare, rapidly fatal disorder which affects about 1 in a million people per year worldwide. It usually affects individuals older than 60. CJD is one of the prion diseases. These disorders occur when the prion protein, a protein normally present in the brain, begins to fold into an abnormal three-dimensional shape. This shape gradually triggers the protein throughout the brain to fold into the same abnormal shape, leading to increasing damage and destruction of brain cells. Prion diseases are unique in that they can be inherited, they can occur sporadically, or they can be infectious. In CJD, depression or agitation tends to occur early. Problems with movement may be present from the beginning or appear shortly after the other symptoms. CJD progresses rapidly and is usually fatal within a year. Summary The word dementia describes a group of symptoms that includes short-term memory loss, confusion, the inability to problem-solve, the inability to complete multi-step activities such as preparing a meal or balancing a checkbook, and, sometimes, personality changes or unusual behavior. Saying that someone has dementia does not offer information about why that person has these symptoms. The diagnosis of dementia requires a complete medical and neuropsychological evaluation. The first step is to determine if the person has a cognitive problem and how severe it is. The next step is to determine the cause in order to accurately recommend treatment and allow patients and caregivers to plan for the future and that brings us full circle it may be dementia, but it doesn t have to be Alzheimer s. 16

17 References 1. Neary, D. (2008) Frontotemporal Lobar Degeneration: An Overview. Retrieved from Smith, J. (2009, September 10). The Role of Neurotransmitters in Dementia. Retrieved from 3. Rabins, P.V. (2011, June 23). Dementia. Retrieved from dementia/vascular-dementia_jhmwp.shtml 4. Levy, J.A. and Chelune (2009, February 26). Cognitive-Behavioral Profiles of Neurodegenerative Dementias: Beyond Alzheimer s Disease. Retrieved from docs/levy_jgpn_07.pdf 5. Vascular Dementia Signs, Symptoms, & Diagnosis. (2013, January 30). Retrieved from 6. Mixed Dementia. (2013) Retrieved from 7. Jagust, W. (2010, June). Dementia with Lewy Bodies. Retrieved from About Dementia: Types of Dementia: Parkinson's Disease. (2013, January 13). Retrieved from 9. Lewy Body Dementias. (2010, November 30). Retrieved from education/diseases/dlb 17