Dementia

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Editor(s)-in-Chief: C. Michael Gibson, M.S.,M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Angela Botts, M.D., Beth Israel Deaconess Medical Center Geriatric Medicine [mailto:abotts@bidmc.harvard.edu]

Overview
Dementia (from Latin de- "apart, away" + mens (genitive mentis) "mind") is the progressive decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal ageing.

Particularly affected areas may be memory, attention, language, and problem solving. Especially in the later stages of the condition, affected persons may be disoriented in time (not knowing what day of the week, day of the month, month, or even what year it is), in place (not knowing where they are), and in person (not knowing who they are).

Symptoms of dementia can be classified as either reversible or irreversible depending upon the etiology of the disease. Less than 10 percent of cases of dementia have been reversed. Dementia is a non-specific term encompassing many disease processes, just as fever is attributable to many etiologies.

Without careful assessment, delirium can easily be confused with dementia and a number of other psychiatric disorders because many of the signs and symptoms are also present in dementia (as well as other mental illnesses including depression and psychosis).

Epidemiology
The prevalence of dementia is rising as the global life expectancy is rising. Particularly in Western countries, there is increasing concern about the economic impact that dementia will have in future, older populaces. In Australia, the 2006 estimated prevalence of dementia is 1.03% of the population as a whole. Though reports of some of the longest living people claim them to be free of it (e.g. Yone Minagawa), it is a disease which is strongly associated with age; 1% of those aged 60-65, 6% of those aged 75-79, and 45% of those aged 95 or older suffer from the disease.

Cortical dementias

 * Alzheimer's disease
 * Vascular dementia (also known as multi-infarct dementia), including Binswanger's disease
 * Dementia with Lewy bodies (DLB)
 * Alcohol-Induced Persisting Dementia
 * Korsakoff's syndrome
 * Wernicke's encephalopathy
 * Frontotemporal lobar degenerations (FTLD), including Pick's disease
 * Frontotemporal dementia (or frontal variant FTLD)
 * Semantic dementia (or temporal variant FTLD)
 * Progressive non-fluent aphasia
 * Creutzfeldt-Jakob disease
 * Dementia pugilistica
 * Moyamoya disease

Subcortical dementias

 * Dementia due to Huntington's disease
 * Dementia due to Hypothyroidism
 * Dementia due to Parkinson's disease
 * Dementia due to Vitamin B1 deficiency
 * Dementia due to Vitamin B12 deficiency
 * Dementia due to Folate deficiency
 * Dementia due to Syphilis
 * Dementia due to Subdural hematoma
 * Dementia due to Hypercalcaemia
 * Dementia due to Hypoglycemia
 * AIDS dementia complex
 * Pseudodementia (associated with clinical depression and bipolar disorder)
 * Substance-induced persisting dementia (related to psychoactive use and formerly Absinthism)
 * Dementia due to multiple etiologies
 * Dementia due to other general medical conditions (i.e. end stage renal failure, cardiovascular disease etc.)
 * Dementia not otherwise specified (used in cases where no specific criteria is met)

Dementia and early onset dementia have been associated with neurovisceral porphyrias. Porphyria is listed in textbooks in the differential diagnosis of dementia. Because acute intermittent porphyria, hereditary coproporphyria and variegate porphyria are aggravated by environmental toxins and drugs the disorders should be ruled out when these etiologies are raised.

Diagnosis
The final diagnosis of dementia is made on the basis of the clinical picture, increasingly with neuroimaging results for backup. For research purposes, the diagnosis depends on both a clinical diagnosis and a pathological diagnosis (i.e., based on the examination of brain tissue, usually from autopsy).

Proper differential diagnosis between the types of dementia (see below) will require, at the least, referral to a specialist, e.g. a geriatric internist, geriatric psychiatrist, neurologist, neuropsychologist or geropsychologist. However, there are some brief (5-15 minutes) tests that have good reliability and can be used in the office or other setting to evaluate cognitive status. Examples of such tests include the abbreviated mental test score (AMTS), the mini mental state examination (MMSE), Modified Mini-Mental State Examination (3MS), the Cognitive Abilities Screening Instrument (CASI) , and the clock drawing test.

An AMTS score of less than six (out of a possible score of ten) and an MMSE score under 24 (out of a possible score of 30) suggests a need for further evaluation. Scores must be interpreted in the context of the person's educational and other background, and the particular circumstances (for example, a person in great pain will not be expected to do well on many tests of mental ability).

Mini-mental state examination
The U.S. Preventive Services Task Force (USPSTF) reviewed tests for cognitive impairment and concluded :
 * MMSE
 * sensitivity 71% to 92%
 * specificity 56% to 96%

A copy of the MMSE can be found in the appendix of the original publication.

Modified Mini-Mental State examination (3MS)
A copy of the 3MS is online. A meta-analysis concluded that the Modified Mini-Mental State (3MS) examination has:
 * sensitivity 83% to 94%
 * specificity 85% to 90%

Abbreviated mental test score
A meta-analysis concluded:
 * sensitivity 73% to 100%
 * specificity 71% to 100%

Other examinations
Many other tests have been studied  including the clock-drawing test example form). Although some may emerge as better alternatives to the MMSE, presently the MMSE is the best studied. However, access to the MMSE is now limited by enforcement of its copyright (details).

Further evaluation includes retesting at another date, and administration of other (and sometimes more complex) tests of mental function, such as formal neuropsychological testing.

Associated Conditions

 * Behavioral disorders
 * Delirium
 * Delusion
 * Depression
 * Hallucinations

Criteria for Diagnosis

 * Amnesia
 * Impairment of abstract thinking
 * Limited judgment ability
 * Orientation disturbances
 * Impairment of higher cognitive functions:
 * Acalculia
 * Agnosia
 * Aphasia
 * Apraxia
 * Personality changes

Severity of Dementia

 * Mild: Independet personal hygiene and judgment are retained, but a reduced performance in social activities or household activities is noticed
 * Medium: Some monitoring necessary, living independently is dangerous
 * Severe: Permanent care and monitoring absolutely necessary, serious loss of independence

History and Symptoms

 * Medication history
 * Abbreviated mental status examination
 * Thorough history needs to be performed to rule out any underlying disease etiology

Laboratory Findings

 * Complete blood count (CBC)
 * Toxicology screening
 * Liver function tests (LFTs)
 * Calcium
 * Blood urea nitrogen (BUN) / creatinine
 * Glucose
 * Thyroid function tests
 * Vitamin B12 levels
 * Folate levels
 * Infectious/inflammatory screenings
 * HIV testing for suspected patients
 * Rapid plasma reagin (RPR) testing for those patients suspected of having syphilis

Electrolyte and Biomarker Studies

 * Electrolytes

Other Diagnostic Studies

 * Genetic testing
 * Cerebrospinal fluid (CSF) analysis is suggested in some cases

Imaging
A CT scan or magnetic resonance imaging (MRI scan) is commonly performed, although these modalities (as is noted below) may not have optimal sensitivity for the diffuse metabolic changes associated with dementia in a patient who 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. Recently, the functional neuroimaging modalities of SPECT and PET have shown quite similar ability to diagnose dementia as clinical exam (PMID 16785801). SPECT's ability to differentiate vascular type from Alzheimer disease types of dementias appears to be superior to clinical exam (PMID 15545324).
 * Electroencephalogram (EEG) may be used to diagnose Creutzfeldt-Jakob disease or underlying metabolic/toxic disorders

Most Common Causes

 * Alcoholism
 * Alzheimer's Disease
 * Binswanger's Disease
 * Drug intoxication
 * Multi-infarct Disease
 * Parkinson's Disease

Less Common Causes

 * Acute intermittent porphyria
 * Adrenal insufficiency
 * Amyotrophic lateral sclerosis
 * Borreliosis
 * Central nervous system (CNS) tumor
 * Cerebral abscess
 * Chronic dysrhythmias
 * Chronic heart failure
 * Chronic hypoglycemia or hypocalcemia
 * Chronic obstructive lung disease
 * Chronic subdural hematoma
 * Conversion reaction
 * Cortical basal degeneration
 * Creutzfeldt-Jakob Disease
 * Cushing's Syndrome
 * Dementia pugilistica
 * Dementia with epilepsy
 * Depression
 * Dialysis dementia
 * Diffuse Lewy Body Disease
 * Frontal lobe dementia
 * General paralysis
 * Hallervorden-Spatz Disease
 * Head trauma
 * Hemochromatosis
 * Hepatic failure
 * Hereditary ataxias
 * Herpes encephalitis
 * HIV encephalopathy
 * Huntington's Disease
 * Hydrocephalus
 * Hyperparathyroidism
 * Hyperthyroidism
 * Hypoparathyroidism
 * Hypothyroidism
 * Lacunar state
 * Leukodystropies
 * Lipid storage disease
 * Meningitis
 * Metastases
 * Multi-infarct dementia
 * Multiple Sclerosis
 * Neurosyphilis
 * Papovavirus
 * Paraneoplastic encephalitis
 * Phenylketonuria
 * Pick's Disease
 * Postanoxia
 * Postinfectious encephalitis
 * Pulmonary failure
 * Recurrent nonconvulsive seizures
 * Renal failure
 * Sarcoidosis
 * Schizophrenia
 * Shy-Drager Syndrome
 * Steel-Richardson Syndrome
 * Subacute sclerosing panencephalitis
 * Syphilis, neurosyphilis
 * Systemic Lupus Erythematosus
 * Toxic disorders (drugs, heavy metals)
 * Tuberculosis
 * Uremic encephalopathy
 * Vitamin deficiencies:
 * B12 deficiency]]
 * Folic acid deficiency
 * Nicotinic acid deficiency
 * Thiamine deficiency
 * Whipple's Disease
 * Wilson's Disease

Treatment
Except for the treatable types listed above, there is no cure to this illness, although scientists are progressing in making a type of medication that will slow down the process. Cholinesterase inhibitors are often used early in the disease course. Cognitive and behavioral interventions may also be appropriate. Educating and providing emotional support to the caregiver (or carer) is of importance as well (see also elderly care).

A Canadian study found that a lifetime of bilingualism has a marked influence on delaying the onset of dementia by an average of four years when compared to monolingual patients. The researchers determined that the onset of dementia symptoms in the monolingual group occurred at the mean age of 71.4, while the bilingual group was 75.5 years. The difference remained even after considering the possible effect of cultural differences, immigration, formal education, employment and even gender as influences in the results.
 * Treat all reversible causes
 * Identify and treat nonreversibly disease etiologies
 * Treat risk factors for those patients with vascular dementia

Pharmacotherapy
Snoezelen rooms that provide patients with a soothing and stimulating environment of light, color, music and scent have been used in the therapy of dementia patients.

Medications

 * Acetylcholinesterase inhibitors

Tacrine (Cognex), donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon) are approved by the United States Food and Drug Administration (FDA) for treatment of dementia induced by Alzheimer disease. They may be useful for other similar diseases causing dementia such as Parkinsons or vascular dementia.


 * N-methyl-D-aspartate Blockers

Drugs within the class known as N-methyl-D-aspartate (NMDA) blockers include memantine (Namenda), which has been approved by the FDA for the treatment of moderate-to-severe dementia.

Acute Pharmacotherapies

 * Alzheimer's Disease
 * Alpha-tocopherol
 * Anticholinesterases
 * Selegiline
 * Parkinson's Disease
 * Anticholinergics
 * Dopamine
 * Dopamine agonists
 * Selegiline

Off label

 * Amyloid deposit inhibitors

Minocycline and Clioquinoline, antibiotics, may help reduce amyloid deposits in the brains of persons with Alzheimer disease.


 * Antipsychotic drugs

Haloperidol (Haldol), risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) are frequently prescribed to help manage psychosis and agitation. Treatment of dementia-associated psychosis or agitation is intended to decrease psychotic symptoms (for example, paranoia, delusions, hallucinations), screaming, combativeness, and/or violence.


 * Antidepressant drugs

Depression is frequently associated with dementia and generally worsens the degree of cognitive and behavioral impairment. Antidepressants may be helpful in alleviating cognitive and behavior symptoms by reuptaking neurotransmitter regulation through reuptake of serotonin, noradrenaline and dopamine.


 * Antianxiety drugs

Many patients with dementia experience anxiety symptoms. Although benzodiazepines like diazepam (Valium) have been used for treating anxiety in other situations, they are often avoided because they may increase agitation in persons with dementia or are too sedating. Buspirone (Buspar) is often initially tried for mild-to-moderate anxiety.

Selegiline, a drug used primarily in the treatment of Parkinson's disease, appears to slow the development of dementia. Selegiline is thought to act as an antioxidant, preventing free radical damage. However, it also acts as a stimulant, making it difficult to determine whether the delay in onset of dementia symptoms is due to protection from free radicals or to the general elevation of brain activity from the stimulant effect.

Prevention
Since there is no cure for dementia, the best an individual can do is to prevent it from developing in the first place.

The main method to prevent dementia is to live an active life, both mentally and physically. It appears that the regular moderate consumption of alcohol (beer, wine or distilled spirits) may reduce risk.

Furthermore, there are medications which might contribute to prevent the onset of dementia, including hypertension medications, anti-diabetic drugs and NSAIDs.

Risk to self & others
Driving with Dementia could lead to severe injury or even death to self and others. Doctors should advise appropriate testing and on when to quit driving.

Services
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.

Dementia: treatable causes
DEMENTIA:
 * Drug toxicity
 * Emotional (depression, anxiety, OCD, etc.)
 * Metabolic (electrolytes, liver dz, kidney dz, COPD)
 * Eyes/ Ears (peripheral sensory restrictions)
 * Nutrition (vitamin, iron deficiencies/ NPH [Normal Pressure Hydrocephalus]
 * Tumors/ Trauma (including chronic subdural hematoma)
 * Infection (meningitis, encephalitis, pneumonia, syphilis)
 * Arteriosclerosis and other vascular disease

Dementia: some common causes
DEMENTIA:
 * Diabetes
 * Ethanol
 * Medication
 * Environmental (eg CO poisoning)
 * Nutritional
 * Trauma
 * Infection
 * Alzheimer's

Dementia: reversible dementia causes
DEMENTIA:
 * Drugs / Depression
 * Elderly
 * Multi-infarct/ Medication
 * Environmental
 * Nutritional
 * Toxins
 * Ischemia
 * Alcohol