Dementia

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Dementia
Alzheimer's disease brain comparison.jpg
Comparison of a normal aged brain (left) and the brain of a person with Alzheimer's (right). Differential characteristics are pointed out.
Classification and external resources
Specialty Neurology, psychiatry
ICD-10 F00-F07
ICD-9-CM 290-294
DiseasesDB 29283
MedlinePlus 000739
eMedicine article/793247
Patient UK Dementia
MeSH D003704
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Dementia, also known as senility,[1] is a broad category of brain diseases that cause a long term and often gradual decrease in the ability to think and remember that is great enough to affect a person's daily functioning.[2] Other common symptoms include emotional problems, problems with language, and a decrease in motivation.[2][3] A person's consciousness is usually not affected.[2] A dementia diagnosis requires a change from a person's usual mental functioning and a greater decline than one would expect due to aging.[2][4] These diseases also have a significant effect on a person's caregivers.[2]

The most common type of dementia is Alzheimer's disease, which makes up 50% to 70% of cases. Other common types include vascular dementia (25%), Lewy body dementia (15%), and frontotemporal dementia.[2][3] Less common causes include normal pressure hydrocephalus, Parkinson's disease, syphilis, and Creutzfeldt–Jakob disease among others.[5] More than one type of dementia may exist in the same person.[2] A small proportion of cases run in families.[6] In the DSM-5, dementia was reclassified as a neurocognitive disorder, with various degrees of severity.[7] Diagnosis is usually based on history of the illness and cognitive testing with medical imaging and blood work used to rule out other possible causes.[8] The mini mental state examination is one commonly used cognitive test.[3] Efforts to prevent dementia include trying to decrease risk factors such as high blood pressure, smoking, diabetes, and obesity.[2] Screening the general population for the disease is not recommended.[9]

There is no cure for dementia.[2] Cholinesterase inhibitors such as donepezil are often used and may be beneficial in mild to moderate disease.[10][11][12] Overall benefit, however, may be minor.[12][13] For people with dementia and those who care for them many measures can improve their lives.[2] Cognitive and behavioral interventions may be appropriate.[2] Educating and providing emotional support to the caregiver is important.[2] Exercise programs are beneficial with respect to activities of daily living and potentially improve outcomes.[14] Treatment of behavioral problems or psychosis due to dementia with antipsychotics is common but not usually recommended due to there often being little benefit and an increased risk of death.[15][16]

Globally, dementia affects 36 million people.[2] About 10% of people develop the disease at some point in their lives.[6] It becomes more common with age.[17] About 3% of people between the ages of 65–74 have dementia, 19% between 75 and 84 and nearly half of those over 85 years of age.[18] In 2013 dementia resulted in about 1.7 million deaths up from 0.8 million in 1990.[19] As more people are living longer, dementia is becoming more common in the population as a whole.[17] For people of a specific age, however, it may be becoming less frequent, at least in the developed world, due to a decrease in risk factors.[17] It is one of the most common causes of disability among the old.[3] It is believed to result in economic costs of 604 billion USD a year.[2] People with dementia are often physically or chemically restrained to a greater degree than necessary, raising issues of human rights.[2] Social stigma against those affected is common.[3]

Signs and symptoms

The symptoms of dementia vary across types and stages of the diagnosis.[20] The most common affected areas include memory, visual-spatial, language, attention and problem solving. Most types of dementia are slow and progressive. By the time the person shows signs of the disease, the process in the brain has been happening for a long time. It is possible for a patient to have two types of dementia at the same time. About 10% of people with dementia have what is known as mixed dementia, which is usually a combination of Alzheimer's disease and another type of dementia such as frontotemporal dementia or vascular dementia.[21][22] Additional psychological and behavioral problems that often affect people who have dementia include:

  • Balance problems
  • Tremor
  • Speech and language difficulty
  • Trouble eating or swallowing
  • Memory distortions (believing that a memory has already happened when it has not, thinking an old memory is a new one, combining two memories, or confusing the people in a memory)
  • Wandering or restlessness
  • Perception and visual problems[23]
  • Behavioral and psychological symptoms of dementia (BPSD) almost always occur in all types of dementia. BPSDs may manifest as:[24]
  • Agitation
  • Depression
  • Anxiety
  • Abnormal motor behavior
  • Elated mood
  • Irritability
  • Apathy
  • Disinhibition and impulsivity
  • Delusions (often believing people are stealing from them) or hallucinations
  • Changes in sleep or appetite.

When people with dementia are put in circumstances beyond their abilities, there may be a sudden change to crying or anger (a "catastrophic reaction").[25]

Depression affects 20–30% of people who have dementia, and about 20% have anxiety.[26] Psychosis (often delusions of persecution) and agitation/aggression also often accompany dementia. Each of these must be assessed and treated independently of the underlying dementia.[27]

Mild cognitive impairment

In the first stages of dementia, the signs and symptoms of the disease may be subtle. Often, the early signs of dementia only become apparent when looking back in time. The earliest stage of dementia is called mild cognitive impairment (MCI). 70% of those diagnosed with MCI progress to dementia at some point.[4] In MCI, changes in the person's brain have been happening for a long time, but the symptoms of the disease are just beginning to show. These problems, however, are not yet severe enough to affect the person’s daily function. If they do, it is considered dementia. A person with MCI scores between 27 and 30 on the Mini-Mental State Examination (MMSE), which is a normal score. They may have some memory trouble and trouble finding words, but they solve everyday problems and handle their own life affairs well.

Early stages

In the early stage of dementia, the person begins to show symptoms noticeable to the people around them. In addition, the symptoms begin to interfere with daily activities. The person usually scores between a 20 and 25 on the MMSE. The symptoms are dependent on the type of dementia a person has. The person may begin to have difficulty with more complicated chores and tasks around the house. The person can usually still take care of him or herself but may forget things like taking pills or doing laundry and may need prompting or reminders.

The symptoms of early dementia usually include memory difficulty, but can also include some word-finding problems (anomia) and problems with planning and organizational skills (executive function). One very good way of assessing a person's impairment is by asking if he or she is still able to handle his/her finances independently. This is often one of the first things to become problematic. Other signs might be getting lost in new places, repeating things, personality changes, social withdrawal and difficulties at work.

When evaluating a person for dementia, it is important to consider how the person was able to function five or ten years earlier. It is also important to consider a person's level of education when assessing for loss of function. For example, an accountant who can no longer balance a checkbook would be more concerning than a person who had not finished high school or had never taken care of his/her own finances.[4]

In Alzheimer's dementia the most prominent early symptom is memory difficulty. Others include word-finding problems and getting lost. In other types of dementia, like dementia with Lewy bodies and fronto-temporal dementia, personality changes and difficulty with organization and planning may be the first signs.

Middle stages

As dementia progresses, the symptoms first experienced in the early stages of the dementia generally worsen. The rate of decline is different for each person. A person with moderate dementia scores between 6-17 on the MMSE. For example, people with Alzheimer's dementia in the moderate stages lose almost all new information very quickly. Dementia sufferers may be severely impaired in solving problems, and their social judgment is usually also impaired. They cannot usually function outside their own home, and generally should not be left alone. They may be able to do simple chores around the house but not much else, and begin to require assistance for personal care and hygiene other than simple reminders.[4]

Late stages

People with late-stage dementia typically turn increasingly inward and need assistance with most or all of their personal care. Persons with dementia in the late stages usually need 24-hour supervision to ensure personal safety, as well as to ensure that basic needs are being met. If left unsupervised, a person with late-stage dementia may wander and fall, may not recognize common dangers around them such as a hot stove, may not realize that they need to use the bathroom or become unable to control their bladder or bowels (incontinent). Changes in eating frequently occur, and those with late-stage dementia often need pureed diets, thickened liquids, and assistance in eating. Their appetite may decline to the point that the person does not want to eat at all. He or she may not want to get out of bed, or may need complete assistance doing so. They may no longer recognize familiar people. He or she may have significant changes in sleeping habits or have trouble sleeping at all.[4]

Causes

Reversible causes

There are four main causes of easily reversible dementia: hypothyroidism, vitamin B12 deficiency, Lyme disease, and neurosyphillis. All people with memory difficulty should be checked for hypothyroidism and B12 deficiency. For Lyme disease and neurosyphilis, testing should be done if there are risk factors for those diseases in the person.[4]

Alzheimer's disease

Brain atrophy in severe Alzheimer's

Alzheimer's disease accounts for up to 50% to 70% of cases of dementia.[2][3] The most common symptoms of Alzheimer's disease are short-term memory loss and word-finding difficulties. People with Alzheimer's also have trouble with visual-spatial areas (for example they may begin to get lost often), reasoning, judgment, and insight. Insight refers to whether or not the person realizes he/she has memory problems.

Common early symptoms of Alzheimer's include repetition, getting lost, difficulties keeping track of bills, problems with cooking especially new or complicated meals, forgetting to take medication, and word-finding problems.

The part of the brain most affected by Alzheimer's is the hippocampus. Other parts of the brain that show shrinking (atrophy) include the temporal and parietal lobes.[4] Although this pattern suggests Alzheimer's, the brain shrinkage in Alzheimer's disease is very variable, and a scan of the brain cannot actually make the diagnosis. The relationship between undergoing anesthesia and AD is unclear.[28]

Vascular dementia

Vascular dementia is the cause of at least 20% of dementia cases, making it the second most common cause of dementia.[29] It is caused by disease or injury to blood vessels that damage the brain, including strokes. The symptoms of this dementia depend on where in the brain the strokes have occurred and whether the vessels are large or small.[4] Multiple injuries can cause progressive dementia over time, while a single injury located in an area critical for cognition (i.e. hippocampus, thalamus) can lead to sudden cognitive decline.[29]

On scans of the brain, a person with vascular dementia may show evidence of multiple different strokes of different sizes. They tend to have risk factors for artery disease such as tobacco smoking, high blood pressure, atrial fibrillation, high cholesterol or diabetes, or other signs of blood vessel disease such as a previous heart attack or angina.

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a dementia that has the primary symptoms of visual hallucinations and "Parkinsonism." Parkinsonism is a term that describes a person with features of Parkinson's disease. This includes tremor, rigid muscles, and a face without emotion. The visual hallucinations in DLB are generally very vivid hallucinations of people and/or animals and they often occur when someone is about to fall asleep or just waking up. Other prominent symptoms include problems with attention, organization, problem solving and planning (executive function), and difficulty with visual-spatial function.[4]

Again, imaging studies cannot necessarily make the diagnosis of DLB, but some signs are particularly common. A person with DLB oftens show occipital hypoperfusion on SPECT scan or occipital hypometabolism on a PET scan. Generally, a diagnosis of DLB is straightforward and unless it is complicated, a brain scan is not always necessary.[4]

Frontotemporal dementia

Frontotemporal dementia (FTD) is a dementia that is characterized by drastic personality changes and language difficulties. In all FTD, the person has a relatively early social withdrawal and early lack of insight into the disease. Memory problems are not a main feature of this disease.[4]

There are three main types of FTD. The first has major symptoms in the area of personality and behavior. This is called behavioral variant FTD (bv-FTD) and is the most common. In bv-FTD, the person shows a change in personal hygiene, becomes rigid in their thinking, and rarely recognize that there is a problem, they are socially withdrawn, and often have a drastic increase in appetite. They may also be socially inappropriate. For example, they may make inappropriate sexual comments, or may begin using pornography openly when they had not before. One of the most common signs is apathy, or not caring about anything. Apathy, however, is a common symptom in many different dementias.[4]

The other two types of FTD feature language problems as the main symptom. The second type is called semantic dementia or temporal variant dementia (TV-FTD). The main feature of this is the loss of the meaning of words. It may begin with difficulty naming things. The person eventually may also lose the meaning of objects as well. For example, a drawing of a bird, dog, and an airplane in someone with FTD may all appear just about the same.[4] In a classic test for this, a patient is shown a picture of a pyramid and below there is a picture of both a palm tree and a pine tree. The person is asked to say which one goes best with the pyramid. In TV-FTD the person would not be able to answer that question.

The last type of FTD is called progressive non-fluent aphasia (PNFA). This is mainly a problem with producing speech. They have trouble finding the right words, but mostly they have a difficulty coordinating the muscles they need to speak. Eventually, someone with PNFA only uses one-syllable words or may become totally mute.

With both TV-FTD and PNFA the symptoms of behavior may be present, but milder and later than in bv-FTD. imaging studies show shrinking of the frontal and temporal lobes of the brain.

Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a form of dementia that is characterized by problems with eye movements. Generally the problems begin with difficulty moving the eyes up and/or down (vertical gaze palsy). Since difficulty moving the eyes upward can sometimes happen in normal aging, problems with downward eye movements are the key in PSP. Other key symptoms of PSP include falls backwards, balance problems, slow movements, rigid muscles, irritability, apathy, social withdrawal, and depression. The person may also have certain "frontal lobe signs" such as perseveration, a grasp reflex and utilization behavior (the need to use an object once you see it). People with PSP often have progressive difficulty eating and swallowing, and eventually with talking as well. Because of the rigidity and slow movements, PSP is sometimes misdiagnosed as Parkinson's disease.

On scans of the brain, the midbrain of people with PSP is generally shrunken (atrophied), but there are no other common brain abnormalities visible on images of the person's brain.

Corticobasal degeneration

Corticobasal degeneration is a rare form of dementia that is characterized by many different types of neurological problems that get progressively worse over time. This is because the disease affects the brain in many different places, but at different rates. One common sign is difficulty with using only one limb. One symptom that is extremely rare in any condition other than corticobasal degeneration is the "alien limb." The alien limb is a limb of the person that seems to have a mind of its own, it moves without control of the person's brain. Other common symptoms include jerky movements of one or more limbs (myoclonus), symptoms that are different in different limbs (asymmetric), difficulty with speech that is due to not being able to move the mouth muscles in a coordinated way, numbness and tingling of the limbs and neglecting one side of the person's vision or senses. In neglect, a person ignores the opposite side of the body from the one that has the problem. For example, a person may not feel pain on one side, or may only draw half of a picture when asked. In addition, the person's affected limbs may be rigid or have muscle contractions causing strange repetitive movements (dystonia).[4]

The area of the brain most often affected in corticobasal degeneration is the posterior frontal lobe and parietal lobe. Still, many other part of the brain can be affected.[4]

Rapidly progressive

Creutzfeldt-Jakob disease typically causes a dementia that worsens over weeks to months, being caused by prions. The common causes of slowly progressive dementia also sometimes present with rapid progression: Alzheimer's disease, dementia with Lewy bodies, frontotemporal lobar degeneration (including corticobasal degeneration and progressive supranuclear palsy).

On the other hand, encephalopathy or delirium may develop relatively slowly and resemble dementia. Possible causes include brain infection (viral encephalitis, subacute sclerosing panencephalitis, Whipple's disease) or inflammation (limbic encephalitis, Hashimoto's encephalopathy, cerebral vasculitis); tumors such as lymphoma or glioma; drug toxicity (e.g., anticonvulsant drugs); metabolic causes such as liver failure or kidney failure; and chronic subdural hematoma.

Other conditions

There are many other medical and neurological conditions in which dementia only occurs late in the illness. For example, a proportion of patients with Parkinson's disease develop dementia, though widely varying figures are quoted for this proportion.[citation needed] When dementia occurs in Parkinson's disease, the underlying cause may be dementia with Lewy bodies or Alzheimer's disease, or both.[30] Cognitive impairment also occurs in the Parkinson-plus syndromes of progressive supranuclear palsy and corticobasal degeneration (and the same underlying pathology may cause the clinical syndromes of frontotemporal lobar degeneration). Chronic inflammatory conditions of the brain may affect cognition in the long term, including Behçet's disease, multiple sclerosis, sarcoidosis, Sjögren's syndrome, and systemic lupus erythematosus. Although the acute porphyrias may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases.

Aside from those mentioned above, inherited conditions that can cause dementia (alongside other symptoms) include:[31]

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Mild cognitive impairment

Mild cognitive impairment basically means that the person exhibits memory or thinking difficulties, but not severe enough yet for a dementia diagnoses.[32] He or she should score between 25-30 on the MMSE.[4] Around 70% of people with MCI go on to develop some form of dementia.[4] MCI is generally divided into two categories. The first is one that is primarily memory loss (amnestic MCI). The second category is anything that is not primarily memory difficulties (non-amnestic MCI). People with primarily memory problems generally go on to develop Alzheimer's disease. People with the other type of MCI may go on to develop other types of dementia.

Diagnosis of MCI is often difficult, as cognitive testing may be normal. Often, more in-depth neuropsychological testing is necessary to make the diagnosis. the most commonly used criteria are called the Peterson criteria and include:

  • Memory or other cognitive (thought-processing) complaint by the person or a person who knows the patient well.
  • The person must have a memory or other cognitive problem as compared to a person of the same age and level of education.
  • The problem must not be severe enough to affect the person's daily function.
  • The person must not have dementia.

Fixed cognitive impairment

Various types of brain injury may cause irreversible cognitive impairment that do not get worse over time. Traumatic brain injury may cause generalized damage to the white matter of the brain (diffuse axonal injury), or more localized damage (as also may neurosurgery). A temporary reduction in the brain's supply of blood or oxygen may lead to hypoxic-ischemic injury. Strokes (ischemic stroke, or intracerebral, subarachnoid, subdural or extradural hemorrhage) or infections (meningitis and/or encephalitis) affecting the brain, prolonged epileptic seizures, and acute hydrocephalus may also have long-term effects on cognition. Excessive alcohol use may cause alcohol dementia, Wernicke's encephalopathy, and/or Korsakoff's psychosis.

Slowly progressive

Dementia that begins gradually and worsens progressively over several years is usually caused by neurodegenerative disease—that is, by conditions that affect only or primarily the neurons of the brain and cause gradual but irreversible loss of function of these cells. Less commonly, a non-degenerative condition may have secondary effects on brain cells, which may or may not be reversible if the condition is treated.

Causes of dementia depend on the age when symptoms begin. In the elderly population (usually defined in this context as over 65 years of age), a large majority of dementia cases are caused by Alzheimer's disease, vascular dementia, or both. Dementia with Lewy bodies is another commonly exhibited form, which again may occur alongside either or both of the other causes.[33][34][35] Hypothyroidism sometimes causes slowly progressive cognitive impairment as the main symptom, and this may be fully reversible with treatment. Normal pressure hydrocephalus, though relatively rare, is important to recognize since treatment may prevent progression and improve other symptoms of the condition. However, significant cognitive improvement is unusual.

Dementia is much less common under 65 years of age. Alzheimer's disease is still the most frequent cause, but inherited forms of the disease account for a higher proportion of cases in this age group. Frontotemporal lobar degeneration and Huntington's disease account for most of the remaining cases.[36] Vascular dementia also occurs, but this in turn may be due to underlying conditions (including antiphospholipid syndrome, CADASIL, MELAS, homocystinuria, moyamoya, and Binswanger's disease). People who receive frequent head trauma, such as boxers or football players, are at risk of chronic traumatic encephalopathy[37] (also called dementia pugilistica in boxers).

In young adults (up to 40 years of age) who were previously of normal intelligence, it is very rare to develop dementia without other features of neurological disease, or without features of disease elsewhere in the body. Most cases of progressive cognitive disturbance in this age group are caused by psychiatric illness, alcohol or other drugs, or metabolic disturbance. However, certain genetic disorders can cause true neurodegenerative dementia at this age. These include familial Alzheimer's disease, SCA17 (dominant inheritance); adrenoleukodystrophy (X-linked); Gaucher's disease type 3, metachromatic leukodystrophy, Niemann-Pick disease type C, pantothenate kinase-associated neurodegeneration, Tay-Sachs disease, and Wilson's disease (all recessive). Wilson's disease is particularly important since cognition can improve with treatment.

At all ages, a substantial proportion of patients who complain of memory difficulty or other cognitive symptoms have depression rather than a neurodegenerative disease. Vitamin deficiencies and chronic infections may also occur at any age; they usually cause other symptoms before dementia occurs, but occasionally mimic degenerative dementia. These include deficiencies of vitamin B12, folate, or niacin, and infective causes including cryptococcal meningitis, HIV, Lyme disease, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, syphilis, and Whipple's disease.

Diagnosis

As seen above, there are many specific types and causes of dementia, often showing slightly different symptoms. However, the symptoms are very similar and it is usually difficult to diagnose the type of dementia by symptoms alone. Diagnosis may be aided by brain scanning techniques. In many cases, the diagnosis cannot be absolutely sure except with a brain biopsy, but this is very rarely recommended (though it can be performed at autopsy). In those who are getting older, general screening for cognitive impairment using cognitive testing or early diagnosis of dementia has not been shown to improve outcomes.[38] However, it has been shown that screening exams are useful in those people over the age of 65 with memory complaints.[4]

Normally, symptoms must be present for at least six months to support a diagnosis.[39] Cognitive dysfunction of shorter duration is called delirium. Delirium can be easily confused with dementia due to similar symptoms. Delirium is characterized by a sudden onset, fluctuating course, a short duration (often lasting from hours to weeks), and is primarily related to a somatic (or medical) disturbance. In comparison, dementia has typically a long, slow onset (except in the cases of a stroke or trauma), slow decline of mental functioning, as well as a longer duration (from months to years).[40]

Some mental illnesses, including depression and psychosis, may produce symptoms that must be differentiated from both delirium and dementia.[41] Therefore, any dementia evaluation should include a depression screening such as the Neuropsychiatric Inventory or the Geriatric Depression Scale.[4] Physicians used to think that anyone who came in with memory complaints had depression and not dementia (because they thought that those with dementia are generally unaware of their memory problems). This is called pseudodementia. However, in recent years researchers have realized that many older people with memory complaints in fact have MCI, the earliest stage of dementia. Depression should always remain high on the list of possibilities, however, for an elderly person with memory trouble.

Cognitive testing

Sensitivity and specificity of common tests for dementia
Test Sensitivity Specificity Reference
MMSE 71%–92% 56%–96% [42]
3MS 83%–93.5% 85%–90% [43]
AMTS 73%–100% 71%–100% [43]

There are some brief tests (5–15 minutes) that have reasonable reliability to screen for dementia. While many tests have been studied,[44][45][46] presently the mini mental state examination (MMSE) is the best studied and most commonly used, albeit some may emerge as better alternatives. Other examples include the abbreviated mental test score (AMTS), the, Modified Mini-Mental State Examination (3MS),[47] the Cognitive Abilities Screening Instrument (CASI),[48] the Trail-making test,[49] and the clock drawing test.[50] The MOCA (Montreal Cognitive Assessment) is a very reliable screening test and is available online for free in 35 different languages.[4] The MOCA has also been shown somewhat better at detecting mild cognitive impairment than the MMSE.[51]

Another approach to screening for dementia is to ask an informant (relative or other supporter) to fill out a questionnaire about the person's everyday cognitive functioning. Informant questionnaires provide complementary information to brief cognitive tests. Probably the best known questionnaire of this sort is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).[52] The Alzheimer's Disease Caregiver Questionnaire is another tool. It is about 90% accurate for Alzheimer's and can be completed online or in the office by a caregiver.[4] On the other hand, the General Practitioner Assessment Of Cognition combines both, a patient assessment and an informant interview. It was specifically designed for the use in the primary care setting.

Clinical neuropsychologists provide diagnostic consultation following administration of a full battery of cognitive testing, often lasting several hours, to determine functional patterns of decline associated with varying types of dementia. Tests of memory, executive function, processing speed, attention, and language skills are relevant, as well as tests of emotional and psychological adjustment. These tests assist with ruling out other etiologies and determining relative cognitive decline over time or from estimates of prior cognitive abilities.

Laboratory tests

Routine blood tests are also usually performed to rule out treatable causes. These tests include vitamin B12, folic acid, thyroid-stimulating hormone (TSH), C-reactive protein, full blood count, electrolytes, calcium, renal function, and liver enzymes. Abnormalities may suggest vitamin deficiency, infection, or other problems that commonly cause confusion or disorientation in the elderly. The problem is complicated by the fact that these cause confusion more often in persons who have early dementia, so that "reversal" of such problems may ultimately only be temporary.[citation needed]

Testing for alcohol and other known dementia-inducing drugs may be indicated.

Imaging

A CT scan or magnetic resonance imaging (MRI scan) is commonly performed, although these tests do not pick up diffuse metabolic changes associated with dementia in a person that shows no gross neurological problems (such as paralysis or weakness) on neurological exam. CT or MRI may suggest normal pressure hydrocephalus, a potentially reversible cause of dementia, and can yield information relevant to other types of dementia, such as infarction (stroke) that would point at a vascular type of dementia.

The functional neuroimaging modalities of SPECT and PET are more useful in assessing long-standing cognitive dysfunction, since they have shown similar ability to diagnose dementia as a clinical exam and cognitive testing.[53] The ability of SPECT to differentiate the vascular cause (i.e., multi-infarct dementia) from Alzheimer's disease dementias, appears superior to differentiation by clinical exam.[54]

Recent research has established the value of PET imaging using carbon-11 Pittsburgh Compound B as a radiotracer (PIB-PET) in predictive diagnosis of various kinds of dementia, in particular Alzheimer's disease. Studies from Australia have found PIB-PET 86% accurate in predicting which patients with mild cognitive impairment will develop Alzheimer's disease within two years. In another study, carried out using 66 patients seen at the University of Michigan, PET studies using either PIB or another radiotracer, carbon-11 dihydrotetrabenazine (DTBZ), led to more accurate diagnosis for more than one-fourth of patients with mild cognitive impairment or mild dementia.[55]

Prevention

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Many prevention measures have been proposed, including lifestyle changes and medication, though none has been reliably shown effective. Among otherwise healthy older people, computerized cognitive training may improve memory. However it is not known if it prevents dementia.[56]

Management

Except for the treatable types listed above, there is no cure. Cholinesterase inhibitors are often used early in the disease course; however, benefit is generally small.[13][57] Cognitive and behavioral interventions may be appropriate. Educating and providing emotional support to the caregiver is of importance as well. Exercise programs are beneficial with respect to activities of daily living and potentially improve dementia.[14]

Psychological therapies

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Psychological therapies for dementia include music therapy with unclear evidence,[58] tentative evidence for reminiscence therapy,[59] some benefit for cognitive reframing for caretakers,[60] unclear evidence for validation therapy,[61] and tentative evidence for mental exercise.[62] Adult daycare centers as well as special care units in nursing homes often provide specialized care for dementia patients. Adult daycare centers offer supervision, recreation, meals, and limited health care to participants, as well as providing respite for caregivers. In addition, home care can provide one-on-one support and care in the home allowing for more individualized attention that is needed as the disease progresses. Psychiatric nurses can make a distinctive contribution to people's mental health.[63]

Since dementia impairs normal communication due to changes in receptive and expressive language, as well as the ability to plan and problem solve, agitated behaviour is often a form of communication for the person with dementia. Actively searching for a potential cause, such as pain, physical illness, or overstimulation can be helpful in reducing agitation.[64] Additionally, using an "ABC analysis of behaviour" can be a useful tool for understanding behavior in people with dementia. It involves looking at the antecedents (A), behavior (B), and consequences (C) associated with an event to help define the problem and prevent further incidents that may arise if the person's needs are misunderstood.[65]

Medications

Currently, no medications have been shown to prevent or cure dementia.[66] Medications may be used to treat the behavioural and cognitive symptoms but have no effect on the underlying disease process.[4][67]

Acetylcholinesterase inhibitors, such as donepezil, may be useful for Alzheimer disease[68] and dementia in Parkinson's, DLB, or vascular dementia.[67] The quality of the evidence however is poor[69] and the benefit is small.[13] No difference has been shown between the agents in this family.[70] In a minority of people side effects include bradycardia and syncope.[71]

As assessment for an underlying cause of the behavior is a needed before prescribing antipsychotic medication for symptoms of dementia.[72] Antipsychotic drugs should be used to treat dementia only if non-drug therapies have not worked, and the person's actions threaten themselves or others.[73][74] Aggressive behavior changes are sometimes the result of other solvable problems, that could make treatment with antipsychotics unnecessary.[73] Because people with dementia can be aggressive, resistant to their treatment, and otherwise disruptive, sometimes antipsychotic drugs are considered as a therapy in response.[73] These drugs have risky adverse effects, including increasing the patient's chance of stroke and death.[73] Generally, stopping antipsychotics for people with dementia does not cause problems, even in those who have been on them a long time.[75]

N-methyl-D-aspartate (NMDA) receptor blockers such as memantine may be of benefit but the evidence is less conclusive than for AChEIs.[76] Due to their differing mechanisms of action memantine and acetylcholinesterase inhibitors can be used in combination however the benefit is slight.[77][78]

Antidepressant drugs: Depression is frequently associated with dementia and generally worsens the degree of cognitive and behavioral impairment. Antidepressants effectively treat the cognitive and behavioral symptoms of depression in patients with Alzheimer's disease,[79] but evidence for their use in other forms of dementia is weak.[80]

It is recommended that benzodiazepines such as diazepam be avoided in dementia due to the risks of increased cognitive impairment and falls.[81] There is little evidence for the effectiveness in this population.[82]

There is no solid evidence that folate or vitamin B12 improves outcomes in those with cognitive problems.[83] Statins also have no benefit in dementia.[84]

Pain

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As people age, they experience more health problems, and most health problems associated with aging carry a substantial burden of pain; therefore, between 25% and 50% of older adults experience persistent pain. Seniors with dementia experience the same prevalence of conditions likely to cause pain as seniors without dementia.[85] Pain is often overlooked in older adults and, when screened for, often poorly assessed, especially among those with dementia since they become incapable of informing others that they're in pain.[85][86] Beyond the issue of humane care, unrelieved pain has functional implications. Persistent pain can lead to decreased ambulation, depressed mood, sleep disturbances, impaired appetite, and exacerbation of cognitive impairment,[86] and pain-related interference with activity is a factor contributing to falls in the elderly.[85][87]

Although persistent pain in the person with dementia is difficult to communicate, diagnose, and treat, failure to address persistent pain has profound functional, psychosocial, and quality of life implications for this vulnerable population. Health professionals often lack the skills and usually lack the time needed to recognize, accurately assess, and adequately monitor pain in people with dementia.[85][88] Family members and friends can make a valuable contribution to the care of a person with dementia by learning to recognize and assess their pain. Educational resources (such as the Understand Pain and Dementia tutorial) and observational assessment tools are available.[85][89][90]

Eating difficulties

Persons with dementia may have difficulty eating. Whenever it is available as an option, the recommended response to eating problems is having a caretaker do assisted feeding for the person.[91] A secondary option for people who cannot swallow effectively is to consider gastrostomy feeding tube placement as a way to give nutrition. However, in bringing person comfort and keeping functional status while lowering risk of aspiration pneumonia and death, assistance with oral feeding is at least as good as tube feeding.[91][92] Tube-feeding is associated with agitation, increased use of physical and chemical restraints, and worsening pressure ulcers. Tube feedings may also cause fluid overload, diarrhea, abdominal pain, local complications, less human interaction, and may increase the risk of aspiration.[93][94]

Benefits of this procedure in those with advanced dementia has not been shown.[95] The risks of using tube feeding include agitation, the person pulling out the tube or otherwise being physically or chemically immobilized to prevent them from doing this, or getting pressure ulcers.[91] There is about a 1% fatality rate directly related to the procedure[96] with a 3% major complication rate.[97]

Alternative medicine

Other therapies that have been studied for effectiveness include aromatherapy with slight evidence,[98][needs update] massage with unclear evidence.[99]

Palliative care

Given the progressive and terminal nature of dementia, palliative care can be helpful to patients and their caregivers by helping both people with the disease and their caregivers understand what to expect, deal with loss of physical and mental abilities, plan out a patient’s wishes and goals including surrogate decision making, and discuss wishes for or against CPR and life support.[100][101] Because the decline can be rapid, and because most people prefer to allow the person with dementia to make his or her own decisions, palliative care involvement before the late stages of dementia is recommended.[102][103]

Epidemiology

Disability-adjusted life year for Alzheimer and other dementias per 100,000 inhabitants in 2002.
  <100
  100-120
  120-140
  140-160
  160-180
  180-200
  200-220
  220-240
  240-260
  260-280
  280–300
  >300

The number of cases of dementia worldwide in 2010 was estimated at 35.6 million.[104] Rates increase significantly with age, with dementia affecting 5% of the population older than 65 and 20–40% of those older than 85.[105] Around two thirds of individuals with dementia live in low and middle income countries, where the sharpest increases in numbers are predicted.[106] Rates are slightly higher in women than men at ages 65 and greater.[105]

In 2013 dementia resulted in about 1.7 million deaths up from 0.8 million in 1990.[19]

History

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Until the end of the 19th century, dementia was a much broader clinical concept. It included mental illness and any type of psychosocial incapacity, including conditions that could be reversed.[107] Dementia at this time simply referred to anyone who had lost the ability to reason, and was applied equally to psychosis of mental illness, "organic" diseases like syphilis that destroy the brain, and to the dementia associated with old age, which was attributed to "hardening of the arteries."

Dementia has been referred to in medical texts since antiquity. One of the earliest known accounts was by the 7th century BC physician and mathematician Pythagoras, who divided the human lifespan into six distinct phases, which were 0-6 (infancy), 7-21 (adolescence), 22-49 (young adulthood), 50-62 (middle age), 63-79 (old age), and 80- (advanced age). The last two he described as the "senium", a period of mental and physical decay, and of the final phase being where "the scene of mortal existence closes after a great length of time that very fortunately, few of the human species arrive at, where the mind is reduced to the imbecility of the first epoch of infancy". In 550 BC, the Athenian statesman and poet Solon argued that the terms of a man's will might be invalidated if he exhibited loss of judgement due to advanced age. Chinese medical texts made allusions to the condition as well, and the characters for "dementia" translate literally to "foolish old person".

Aristotle and Plato both spoke of the mental decay of advanced age, but apparently simply viewed it as an inevitable process that affected all old men, and which nothing could prevent. The latter stated that the elderly were unsuited for any position of responsibility because, "There is not much acumen of the mind that once carried them in their youth, those characteristics one would call judgement, imagination, power of reasoning, and memory. They see them gradually blunted by deterioration and can hardly fulfill their function."

For comparison, the Roman statesman Cicero held a view much more in line with modern-day medical wisdom that loss of mental function was not inevitable in the elderly and "affected only those old men who were weak-willed". He spoke of how those who remained mentally active and eager to learn new things could stave off dementia. However, Cicero's views on aging, although progressive, were largely ignored in a world that would be dominated by Aristotle's medical writings for centuries. Subsequent physicians during the time of Roman Empire such as Galen and Celsus simply repeated the beliefs of Aristotle while adding few new contributions to medical knowledge.

Byzantine physicians sometimes wrote of dementia, and it is recorded that at least seven emperors whose lifespans exceeded the age of 70 displayed signs of cognitive decline. In Constantinople, there existed special hospitals to house those diagnosed with dementia or insanity, but these naturally did not apply to the emperors who were above the law and whose health conditions could not be publicly acknowledged.

Otherwise, little is recorded about senile dementia in Western medical texts for nearly 1700 years. One of the few references to it was the 13th century friar Roger Bacon, who viewed old age as divine punishment for original sin. Although he repeated existing Aristotelian beliefs that dementia was inevitable after a long enough lifespan, he did make the extremely progressive assertion that the brain was the center of memory and thought rather than the heart.

Poets, playwrights, and other writers however made frequent allusions to the loss of mental function in old age. Shakespeare notably mentions it in some of his plays including Hamlet and King Lear.

Dementia in the elderly was called senile dementia or senility, and viewed as a normal and somewhat inevitable aspect of growing old, rather than as being caused by any specific diseases. At the same time, in 1907, a specific organic dementing process of early onset, called Alzheimer's disease, had been described. This was associated with particular microscopic changes in the brain, but was seen as a rare disease of middle age because the first patient diagnosed with it was a 50-year-old woman.

During the 19th century, doctors generally came to believe that dementia in the elderly was the result of cerebral atheroslerosis, although opinions fluctuated between the idea that it was due to blockage of the major arteries supplying the brain or small strokes within the vessels of the cerebral cortex. This viewpoint remained conventional medical wisdom through the first half of the 20th century, but by the 1960s was increasingly challenged as the link between neurodegenerative diseases and age-related cognitive decline was established. By the 1970s, the medical community maintained that vascular dementia was rarer than previously thought and Alzheimer's Disease caused the vast majority of mental impairments in old age. More recently however, it is believed that dementia is often a mixture of both conditions.

Much like other diseases associated with aging, dementia was comparatively rare before the 20th century, due to the fact that it is most common in people over 80, and such lifespans were uncommon in preindustrial times. Conversely, syphilitic dementia was widespread in the developed world until largely being eradicated by the use of penicillin after WWII. With significant increases in life expectancy following WWII, the number of people in developed countries over 65 started rapidly climbing. While elderly persons constituted an average of 3-5% of the population prior to 1945, by 2010 it was common in many countries to have 10-14% of people over 65 and in Germany and Japan, this figure exceeded 20%. Public awareness of Alzheimer's Disease was greatly increased in 1994 when former US president Ronald Reagan announced that he was suffering from the condition.

By the period of 1913–20, schizophrenia had been well-defined in a way similar to today, and also the term dementia praecox had been used to suggest the development of senile-type dementia at a younger age. Eventually the two terms fused, so that until 1952 physicians used the terms dementia praecox (precocious dementia) and schizophrenia interchangeably. The term precocious dementia for a mental illness suggested that a type of mental illness like schizophrenia (including paranoia and decreased cognitive capacity) could be expected to arrive normally in all persons with greater age (see paraphrenia). After about 1920, the beginning use of dementia for what we now understand as schizophrenia and senile dementia helped limit the word's meaning to "permanent, irreversible mental deterioration." This began the change to the more recognizable use of the term today.

In 1976, neurologist Robert Katzmann suggested a link between senile dementia and Alzheimer's disease.[108] Katzmann suggested that much of the senile dementia occurring (by definition) after the age of 65, was pathologically identical with Alzheimer's disease occurring before age 65 and therefore should not be treated differently. He noted that the fact that "senile dementia" was not considered a disease, but rather part of aging, was keeping millions of aged patients experiencing what otherwise was identical with Alzheimer's disease from being diagnosed as having a disease process, rather than simply considered as aging normally.[109] Katzmann thus suggested that Alzheimer's disease, if taken to occur over age 65, is actually common, not rare, and was the 4th or 5th leading cause of death, even though rarely reported on death certificates in 1976.

This suggestion opened the view that dementia is never normal, and must always be the result of a particular disease process, and is not part of the normal healthy aging process, per se. The ensuing debate led for a time to the proposed disease diagnosis of "senile dementia of the Alzheimer's type" (SDAT) in persons over the age of 65, with "Alzheimer's disease" diagnosed in persons younger than 65 who had the same pathology. Eventually, however, it was agreed that the age limit was artificial, and that Alzheimer's disease was the appropriate term for persons with the particular brain pathology seen in this disease, regardless of the age of the person with the diagnosis. A helpful finding was that although the incidence of Alzheimer's disease increased with age (from 5–10% of 75-year-olds to as many as 40–50% of 90-year-olds), there was no age at which all persons developed it, so it was not an inevitable consequence of aging, no matter how great an age a person attained. Evidence of this is shown by numerous documented supercentenarians (people living to 110+) that experienced no serious cognitive impairment. There is some evidence that dementia is most likely to develop between the ages of 80-84 and individuals who pass that point without being affected have a lower chance of developing it. Women account for a larger percentage of dementia cases than men, although this can be attributed to their longer overall lifespan and greater odds of attaining an age where the condition is likely to occur.

Also, after 1952, mental illnesses like schizophrenia were removed from the category of organic brain syndromes, and thus (by definition) removed from possible causes of "dementing illnesses" (dementias). At the same, however, the traditional cause of senile dementia– "hardening of the arteries" – now returned as a set of dementias of vascular cause (small strokes). These were now termed multi-infarct dementias or vascular dementias.

In the 21st century, a number of other types of dementia have been differentiated from Alzheimer's disease and vascular dementias (these two being the most common types). This differentiation is on the basis of pathological examination of brain tissues, symptomatology, and by different patterns of brain metabolic activity in nuclear medical imaging tests such as SPECT and PETscans of the brain. The various forms of dementia have differing prognoses (expected outcome of illness), and also differing sets of epidemologic risk factors. The causal etiology of many of them, including Alzheimer's disease, remains unclear, although many theories exist such as accumulation of protein plaques as part of normal aging, inflammation (either from bacterial pathogens or exposure to toxic chemicals), inadequate blood sugar, and traumatic brain injury.

Society and culture

Many countries consider the care of people living with dementia a national priority and invest in resources and education to better inform health and social service workers, unpaid caregivers, relatives, and members of the wider community. Several countries have national plans or strategies.[110] In these national plans, there is recognition that people can live well with dementia for a number of years, as long as there is the right support and timely access to a diagnosis. David Cameron has described dementia as being a "national crisis", affecting 800,000 people in the United Kingdom.[111]

In the United Kingdom, as with all mental disorders, where a person with dementia could potentially be a danger to themselves or others, they can be detained under the Mental Health Act 1983 for the purposes of assessment, care and treatment. This is a last resort, and usually avoided if the patient has family or friends who can ensure care.

Driving with dementia could lead to severe injury or even death to self and others. Doctors should advise appropriate testing on when to quit driving.[112] The United Kingdom DVLA (Driver & Vehicle Licensing Agency) states that people with dementia who specifically have poor short term memory, disorientation, or lack of insight or judgment are not fit to drive, and in these instances the DVLA must be informed so that the driving licence can be revoked. They do, however, acknowledge low-severity cases and those with an early diagnosis, and those drivers may be permitted to drive pending medical reports.

Many support networks are available to dementia sufferers and their families and caregivers. Several charitable organisations aim to raise awareness and campaign for the rights of people living with dementia. There is also support and guidance on assessing testamentary capacity in people who have dementia.[113]

References

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  18. Lua error in package.lua at line 80: module 'strict' not found.
  19. 19.0 19.1 Lua error in package.lua at line 80: module 'strict' not found.
  20. "Dementia". American Speech Language Hearing Association. Retrieved from http://www.asha.org/PRPSpecificTopic.aspx?folderid=8589935289&section=Signs_and_Symptoms
  21. What is vascular dementia? Alzheimer's Society.
  22. Lua error in package.lua at line 80: module 'strict' not found.
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  102. http://pmj.sagepub.com/content/early/2013/07/05/0269216313493685.full.pdf+html
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External links