Dementia

Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform everyday activities. Dementia may involve problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process. Dementia is currently the seventh leading cause of death worldwide and has 10 million new cases reported every year (approximately one every three seconds).

History

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 reversible conditions. Dementia at this time simply referred to anyone who had lost the ability to reason, and was applied equally to psychosis, "organic" diseases like syphilis that can destroy the brain, and to the dementia associated with old age, which was attributed to "hardening of the arteries".

In Roman times, philosopher Emperor Marcus Aurelius, who lived from 161 to 180 C.E., feared falling into a state of dementia more than he feared death. He wrote:

"...if we live longer, there is no guarantee that our mind will likewise retain that power to comprehend and study the world which contributes to our experience of things divine and human. If dementia sets in, there will be no failure of such faculties as breathing, feeding, imagination, desire: before these go, the earlier extinction is of one's proper use of oneself, one's accurate assessment of the gradations of duty, one's ability to analyse impressions, one's understanding of whether the time has come to leave this life - these and all other matters which wholly depend on trained calculation. So we must have a sense of urgency, not only for the ever closer approach of death, but also because our comprehension of the world and our ability to pay proper attention will fade before we do." --Meditations 3:1, Marcus Aurelius

Possible causes

Various diseases and injuries to the brain, such as stroke, can give rise to dementia. However, the most common cause is Alzheimer's disease, a neurodegenerative disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has re-described dementia as a mild or major neurocognitive disorder with varying degrees of severity and many causative subtypes. The International Classification of Diseases (ICD-11) also classifies dementia as a neurocognitive disorder (NCD) with many forms or subclasses. Dementia is listed as an acquired brain syndrome, marked by a decline in cognitive function, and is contrasted with neurodevelopmental disorders. It is also described as a spectrum of disorders with causative subtypes of dementia based on a known disorder, such as Parkinson's disease for Parkinson's disease dementia, Huntington's disease for Huntington's disease dementia, vascular disease for vascular dementia, HIV infection causing HIV dementia, frontotemporal lobar degeneration for frontotemporal dementia, Lewy body disease for dementia with Lewy bodies, and prion diseases. Subtypes of neurodegenerative dementias may also be based on the underlying pathology of misfolded proteins, such as synucleinopathies and tauopathies. The coexistence of more than one type of dementia is known as mixed dementia.

Many neurocognitive disorders may be caused by another medical condition or disorder, including brain tumors and subdural hematoma, endocrine disorders such as hypothyroidism and hypoglycemia, nutritional deficiencies including of thiamine and niacin, infections, immune disorders, liver or kidney failure, metabolic disorders such as Kufs disease, some leukodystrophies, and neurological disorders such as epilepsy and multiple sclerosis. Some of the neurocognitive deficits may sometimes show improvement with treatment of the causative medical condition.

Decades of published scientific research strongly implicate long-term exposure to low levels of aluminum in the development of Alzheimer's disease. This dementia was completely unknown to medicine before the proliferation of aluminum throughout industrialized societies beginning in the late 19th century.

Signs and symptoms

The signs and symptoms of dementia are termed as the neuropsychiatric symptoms—also known as the behavioral and psychological symptoms—of dementia. The behavioral symptoms can include agitation, restlessness, inappropriate behavior, sexual disinhibition, and verbal or physical aggression. These symptoms may result from impairments in cognitive inhibition. The psychological symptoms can include depression, hallucinations (most often visual), delusions, apathy, and anxiety. The most commonly affected areas of brain function include memory, language, attention, problem solving, and visuospatial function affecting perception and orientation. The symptoms progress at a continuous rate over several stages, and they vary across the dementia subtypes. Most types of dementia are slowly progressive with some deterioration of the brain well established before signs of the disorder become apparent. There are often other conditions present, such as high blood pressure or diabetes, and there can sometimes be as many as four of these comorbidities.

Signs of dementia include getting lost in a familiar neighborhood, using unusual words to refer to familiar objects, forgetting the name of a close family member or friend, forgetting old memories, and being unable to complete tasks independently, such as paying bills or balancing a checkbook.

People with dementia are more likely to have problems with incontinence than those of a comparable age without dementia; they are three times more likely to have urinary incontinence and four times more likely to have fecal incontinence.

Stages

The course of dementia is often described in four stages – pre-dementia, early, middle, and late, that show a pattern of progressive cognitive and functional impairment. More detailed descriptions can be arrived at by the use of numeric scales. These scales include the Global Deterioration Scale for Assessment of Primary Degenerative Dementia (GDS or Reisberg Scale), the Functional Assessment Staging Test (FAST), and the Clinical Dementia Rating (CDR). Using the GDS, which more accurately identifies each stage of the disease progression, a more detailed course is described in seven stages – two of which are broken down further into five and six degrees. Stage 7(f) is the final stage.

Classification

Vascular dementia can affect both cortical and subcortial locations.

Cortical dementias

Among the many causes of cortical dementia, common causes are:

• Alzheimer's disease which usually affects posterior cortical regions before progressing to the frontal cortex.
• Frontotemporal lobar degeneration (Pick's Disease)
• Dementia with Lewy bodies

Subcortical dementias

Among the many causes of subcortical dementia, common causes are Parkinson's disease, vitamin B12 deficiency, and some vascular dementias.

Epidemiology

The number of cases of dementia worldwide in 2021 was estimated at 55 million, with close to 10 million new cases each year. According to a report by the World Health Organization, "In 2021, Alzheimer’s disease and other forms of dementia ranked as the seventh leading cause of death, killing 1.8 million lives." By 2050, the number of people living with dementia is estimated to be over 150 million globally. Around 7% of people over the age of 65 have dementia, with slightly higher rates (up to 10% of those over 65) in places with relatively high life expectancy. In the United States, an estimated 40% of those over the age of 85 years old will eventually develop Alzheimer's dementia. The prevalence of dementia differs in different world regions, ranging from 4.7% in Central Europe to 8.7% in North Africa/Middle East; the prevalence in other regions is estimated to be between 5.6 and 7.6%. The number of people living with dementia is estimated to double every 20 years. In 2016 dementia resulted in about 2.4 million deaths, up from 0.8 million in 1990.

The annual incidence of dementia diagnosis is nearly 10 million worldwide. Almost half of new dementia cases occur in Asia, followed by Europe (25%), the Americas (18%), and Africa (8%). The incidence of dementia increases exponentially with age, doubling with every 6.3-year increase in age. Rates are slightly higher in women than men at ages 65 and greater. The disease trajectory is varied and the median time from diagnosis to death depends strongly on age at diagnosis, from 6.7 years for people diagnosed aged 60–69 to 1.9 years for people diagnosed at 90 or older.

Dementia impacts not only individuals with dementia, but also their carers and the wider society. Among people aged 60 years and over, dementia is ranked the ninth most burdensome condition according to the 2010 Global Burden of Disease (GBD) estimates. The global costs of dementia was around U.S. $818 billion in 2015, a 35.4% increase from U.S. $604 billion in 2010.

A new 2024 study reveals that deaths from dementia in the U.S. have tripled in the past 21 years, rising from around 150,000 in 1999 to over 450,000 in 2020; the likelihood of dying from dementia increased across all demographic groups studied.

Diagnosis

Symptoms are similar across dementia types, and it is difficult to diagnose by symptoms alone. Diagnosis may be aided by brain scanning techniques. In many cases, the diagnosis requires a brain biopsy to become final, but this is 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. However, screening exams are useful in 65+ persons with memory or function complaints.

Normally, symptoms must be present for at least six months to support a diagnosis. 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 trajectory (from months to years).

Four functional symptoms

Diagnosis of dementia is usually based on medical history and cognitive testing with imaging. Blood tests may be taken to rule out other possible causes that may be reversible, such as hypothyroidism, and to determine the dementia subtype. One commonly used cognitive test is the mini–mental state examination. Although the greatest risk factor for developing dementia is aging, dementia is not a normal part of the aging process; many people aged 90 and above show no signs of dementia. Several risk factors for dementia, such as smoking and obesity, are preventable by lifestyle changes.

Deficits in cognitive function contribute to impaired functional status. The deficits in the domains of cognitive function are:

• Agnosia - "Failure to recognize or identify objects despite intact sensory function"
• Aphasia - "Deterioration of language function"
• Apraxia - "Impaired ability to execute motor activities despite intact motor abilities, sensory function, and comprehension of the required task"
• Disturbance in executive functioning - "The ability to think abstractly and to plan, initiate, sequence, monitor, and stop complex behavior"

Ascertainment of decision-making capacity

Decision making can be assessed with the Aid to Capacity Evaluation (ACE).

Consequences of labeling

In one study, learning of having mild cognitive impairment reduced stress.

Mental status schedules

Systematic reviews have compared the schedules.

A separate systematic review has examined decision making capacity.

Temporal disorientation

Among hospitalized geriatric patients, "failure to identify either year or month correctly was 95% sensitive and 86.5% specific for the detection of cognitive impairment".

Sweet 16

The Sweet 16 is available online at http://hospitalelderlifeprogram.org/private/sweet16-disclaimer.php?pageid=01.09.00. Accuracy using a score of less than 14:

• sensitivity 99%
• specificity 72%

Mini-cog

According to the systematic review by the Rational Clinical Examination, regarding the mini-cog "the performance of the Mini-Cog...cannot be determined with confidence because none of these screens were actually administered in their suggested forms. However, the performance suggested by the retrospective analyses reported in these articles is promising." More recent studies and reviews are favorable. The mini-COG is available at http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/clock_drawing_test.pdf and http://geriatrics.uthscsa.edu/tools/MINICog.pdf .

Mini-mental state examination

The Mini-mental state examination (MMSE) is the most studied test. A systematic review concluded that the accuracy of the MMSE is:

• sensitivity 71% to 92%
• specificity 56% to 96%

Copies of their MMSE can be purchased (http://www4.parinc.com/Products/Product.aspx?ProductID=MMSE). A copy of the Mini-mental state examination can be found in the appendix of the original publication.

Modified Mini-Mental State examination (3MS)

A meta-analysis concluded that the Modified Mini-Mental State (3MS) examination has:

• sensitivity 83% to 94%
• specificity 85% to 90%

A copy of the 3MS is online.

Abbreviated mental test score

A meta-analysis concluded:

sensitivity 73% to 100%

specificity 71% to 100%

Clinical Dementia Rating

The Clinical Dementia Rating scale can quantify severity of functional impairment.

St Louis University mental status examination (SLUMS)

The SLUMS has been compared to the MMSE. Both evaluations were by the developer of the SLUMS and showed comparable accuracy to the MMSE.

Other examinations

Many other tests have been studied including the Executive Interview (EXIT).

Investigation of causes

Among rapidly progressive cases, causes include: sporadic, e.g., Creutzfeldt-Jakob disease (sCJD), immunological (vasculitis, encephalomyelitis, and limbic encephalitis), cancer (mainly lymphoma), infectious (fungal, viral, and parasitic), and metabolic (including Wernicke encephalopathy) causes.

Laboratory tests

Apolipoprotein E4

Although apolipoprotein E4 is an important susceptibility gene for Alzheimer's disease, its sensitivity and specificity are insufficient (65 and 68 percent, respectively) to be used as a diagnostic test.

Apolipoprotein E4 does not added to other tests in predicting who will develop Alzheimer's.

Treatment

Approaches to treatment

"Actively involving caregivers in making choices about treatments" my be the most important way to delay institutionalization of patients with dementia.

The use of care managers may help.

Non drug treatments

Behavior management techniques (BMT)

Behavior management techniques (BMT) might help. More specifically, " interventions that address behavioral issues and unmet needs" may help.

Exercise

Home-based program of physical activity might benefit according to a randomized controlled trial.

Medications

As of 2024, especially regarding Alzheimer's, there are generally no effective medications to either reverse or halt dementia progression. This includes new drugs such as the Alzheimer's anti-beta amyloid monoclonal antibody drug leqembi, which slightly slows the progression of Alzheimer's but does not stop it.

Cholinesterase inhibitors. Available cholinesterase inhibitors drugs are donepezil, galantamine, rivastigmine, and tacrine.

Neuropeptide modifier. Memantine is a neuropeptide modifier that acts on the N-methyl-D-aspartate (NMDA) cell surface receptors for the neurotransmitter glutamate.

Anti-psychotics. The newer, atypical antipsychotic agents (olanzapine, quetiapine, risperidone), were found to have "adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease." A more recent randomized controlled trial that compared the second generation anti-psychotic agents found that none improved functioning, care needs, or quality of life with statistical significance; however, olanzapine and risperidone may reduce anger. Regardless, antipsychotic agents may increase mortality.

Withdrawing psychotropics agents may prevent accidental falls.

Melatonin. Melatonin mayor may not help with associated sleep and behavior disturbance.

Dietary supplements. Ginkgo biloba has conflicting evidence regarding its efficacy.

Analgesics. Treating pain may reduce agitation.

Prevention

Risk factors for dementia include high blood pressure, high levels of cholesterol, vision loss, hearing loss, smoking, obesity, depression, inactivity, diabetes, lower levels of education, and low social contact. Overindulgence in alcohol, lack of sleep, anemia, traumatic brain injury, and air pollution can also increase the chance of developing dementia. Many of these risk factors, including the lower level of education, smoking, physical inactivity and diabetes, are modifiable. Several of the group are known as vascular risk factors. Managing these risk factors can reduce the risk of dementia in individuals in their late midlife or older age. A reduction in a number of these risk factors, such as switching to a high-fiber, low-fat, plant-based diet or quitting cigarette smoking, can give a positive outcome. The decreased risk achieved by adopting a healthy lifestyle is seen even in those with a high genetic risk.

The standard American diet high in animal products and dairy and concomitant elevated levels of saturated fat is associated with a greater risk of developing dementia. Population and clinical research studies show that plant-based diets low in animal products and high in starch, fruits, and vegetables are associated with lower risk.

Most, but not all studies find that physical activity is associated with reduced risk of dementia. These observational studies cannot prove cause and effect.

Maintaining activities such as cognitive games and reading, playing musical instruments, and physical activities are associated with reduced the risk of dementia in an observational study.

Various medications have been associated with progression or prevention (cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, renin-angiotensin system blockers, and hydroxymethylglutaryl-coenzyme A reductase inhibitors) of dementia.

Observational, non-randomized cohort studies suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) may or may not prevent dementia.

Ginkgo biloba does not prevent dementia according to a large randomized controlled trial and systematic review by the Cochrane Collaboration in spite of earlier studies that were positive.

Screening

Practice guidelines

In 2003, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) gave a grade I recommendation, indicating "the evidence is insufficient to recommend for or against routine screening for dementia in older adults".

Evidence

The late-life dementia risk index:

late-life dementia risk index

Risk	Score	Incidence of dementia within 6 years
High	≥8	56%
Intermediate	4-7	23%
Low	0-3	4%
Based on Table 3 from Barnes et al.

• older age (1–2 points)
• poor cognitive test performance (2–4 points)
• body mass index <18.5 (2 points)
• ≥1 apolipoprotein E 4 alleles (1 point)
• cerebral MRI findings of white matter disease (1 point)
• cerebral ventricular enlargement (1 point)
• internal carotid artery thickening on ultrasonography (1 point)
• history of coronary artery bypass surgery (1 point)
• slow physical performance (1 point)
• lack of alcohol consumption (1 point)

Prognosis

Functional Assessment Staging (FAST) scale Stage 6 6a = inability to dress 6b = inability to bathe 6c = inability to toilet 6d = urinary incontinence at least occasionally 6e = bowel incontinence at least occasionally Stage 7 7a = speech is limited to less than 5 words 7b = all intelligible vocabulary is lost 7c = nonambulatory 7d = unable to sit independently 7e = unable to smile 7f = unable to hold head up

Mild cognitive impairment

Mortality is increased with mild cognitive impairment. A systematic review of cohort studies concluded that the rate conversion of mild cognitive impairment to dementia is about 4% per year."

Once a patient has advanced dementia, defined as a score of 5 or 6 on the Cognitive Performance Scale from the most recent Minimum Data Set assessment (a score of 5 corresponds to a score of 5.1 (95% CI: ±10) on the Folstein Mini–Mental State Examination, the median survival is about 18 months.

Dementia

Mortality can also be predicted by Medicare guidelines for use of Hospice. If the patients is a stage 7c on the Functional Assessment Staging (FAST) scale and has had a prior complication of dementia such aspiration pneumonia, stage 4 or more pressure ulcer, upper urinary tract infection, or inability to eat, then mortality is predicted at 6 months with accuracy of:

• Sensitivity 20%
• Specificity 89%

Similarly, mortality can be predicted by the ADEPT score.

Legal issues

As of 2024, when improved healthcare means that many people are living longer, there is growing concern about dementia, not just in aging patients but as a result of other health challenges. However, physicians often do not agree among themselves on how to detect and define it. And a medical diagnosis of dementia can have serious legal consequences, resulting (just for example) in a patient losing the right to manage their own finances or make their own medical decisions. Thus, in the U.S., physicians "recommend" that Medicare patients (age 65 and over) be given a cognitive test as part of their annual wellness exam, but they stopped short of requiring such a test.

Attribution

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