• 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 aging. (Wiki)

• significant loss of intellectual abilities such as memory capacity, severe enough to interfere with social or occupational functioning.
• as a memory syndrome, dementia is characterized by:
  1. impairment in memory,
  2. impairment in another area of thinking such as the ability to organize thoughts and reason, the ability to use language, or the ability to see accurately the visual world (not because of eye disease), and
  3. these impairments are severe enough to cause a decline in the patient's usual level of functioning.

• Dementia is reported in as many as 1% of adults 60 years of age
• the frequency of dementia increases every five years after 60 years of age (ref)
• greater risk in women than men (ref)

• brain disorder named for German physician Alois Alzheimer
  • first described it in 1906
  • a 51-year-old woman (Auguste D.) brought to see him in 1901 by her family.
  • Patient had developed problems with memory, unfounded suspicions that her husband was unfaithful, and difficulty speaking and understanding what was said to her.
  • Symptoms rapidly grew worse, and within a few years she was bedridden.
  • died in Spring 1906, of overwhelming infections from bedsores and pneumonia.
  • Dr. Alzheimer had never before seen anyone like Auguste D., gained the family's permission to perform an autopsy.
  • In Auguste's brain, he saw dramatic shrinkage, especially of the cortex.
  • Under the microscope, he also saw widespread fatty deposits in small blood vessels, dead and dying brain cells, and abnormal deposits in and around cells.
  • in 1907, Alzheimer published his observations about Auguste D.
  • in 1910, Emil Kraepelin, a psychiatrist noted for his work in naming and classifying brain disorders, proposed that the disease be named after Alzheimer.

• a progressive and fatal brain disease.
• As many as 5 million Americans are living with Alzheimer's disease. (magnitude)
• Projections to 7+ mil in 2030, 16+ mil in 2050 (Alz. Assoc)
• Generally affects individuals 65+, "early-onset refers" to Alzheimer's that occurs in a person under age 65.
• Today it is the seventh-leading cause of death in the United States. (ref1, ref2)
• Alzheimer's destroys brain cells, causing cortical atrophy (.jpg)
• Healthy cells are destroyed by neurofibrillary plaques and tangles (.gif)

• Diagnosis:
  • Diagnosed as "dementia, Alzheimer's type" according to clinical presentation. Confirmative diagnosis made upon inspection of cellular tissue at autopsy
  • Recent diagnostic blood test developed (link)

    The test measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.

    Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.

  • Research points towards "brain markers" on fMRI (bad link, good link, actual article)

    In this study, researchers conducted fMRI scans on 75 people, including 34 with mild cognitive impairment, 13 with Alzheimer's disease and 28 with normal cognition. Study participants completed standard neuropsychological testing and were monitored with fMRI while performing a memory task matching names and faces. Patients were then followed for three and a half years to determine how their cognition changed over time.

    The researchers found that approximately a third of the MCI subjects converted to Alzheimer's in three and half years after their initial scans. The conversion to Alzheimer's was determined by study doctors using routine clinical and memory tests. fMRI level of deactivation was found to significantly predict which MCI subjects converted to Alzheimer's.

• Progresses through stages (3-min video):
  1. Early/mild: mild memory lapses, confusion, some personality changes, may need minimal assistance with simple daily routines
  2. Middle/Moderate: rapid loss of cognitive function, loss of immediate memory, some loss of long-term memory, indreased dependence on others for ADLs
  3. Late/Severe: Loss of new and long-term memory, bodily regulation

• Confabulation (Sachs, A Matter of Identity)

  He never stops, he's like a man in a race, a man trying to catch something which eludes him. And indeed he can never stop running, for the breach in memory, in existence, in meaning, is never healed, but has to be bridged, to be "'patched' every second. And the bridges, the patches, for all their brilliance, fail to work - because they are confabulations, fictions, which cannot do service for reality, while also failing to correspond with reality.

• Treatment: certain medications seem to slow its general progress to some degree in the early stages and others can help with mood changes and other specific behavioral problems of the disease.
• There is no cure. Alzheimer's gets worse over time, and it is fatal.
  • Cognex.
    • In 1993, Cognex became the first drug approved by the FDA for treatment of Alzheimer's disease.
    • The drug works by slowing the breakdown of acetylcholine.
    • can help relieve some of the memory impairment associated with the disease.
    • Numerous side effects, not well tolerated
  • Aricept, Exelon and Razadyne(formerly known as Reminyl).
    • These medications work by the same mechanism as Cognex
    • They can improve mental functioning in early cases and perhaps delay the need for nursing home care, but do not seem to delay the actual progression of the disease
  • Namenda.
    a newer drug approved in October 2003
    • works by blocking glutamate which may be overactive in someone with Alzheimer's disease.
    • It improves mental function and may be more effective in moderate to severe symptoms

• Prevention:
  • Brain Exercise? (link)

    The results of the study were recently published in the New England Journal of Medicine (N Engl J Med 2003;348:2508-16). The researchers found that over an average period of 5.4 years, dementia developed in 124 subjects (Alzheimer's disease in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). They also found that among leisure activities, reading, playing board games, playing musical instruments, and dancing were associated with a reduced risk of dementia!

  • Drinking wine? (link)

    Lissner and her team looked at 1,462 women who ranged in age from 38 to 60 between 1968 and 1969 and were followed up to 2002, by which time 164 had been diagnosed with dementia. The women reported their alcohol consumption at the beginning of the study and three more times during the course of the study. The risk of developing dementia was 40 percent lower among wine drinkers, the researchers found, while women who drank wine and no other alcohol had a 70 percent lower risk. Smokers were even more strongly protected against dementia if they drank wine only. But women who drank spirits were at 50 percent greater risk of dementia.

Vascular Dementia

• Also known as Multi-infarct dementia (Images: image)
• is the second most common form of dementia after Alzheimer disease (AD) in the elderly (persons over 65 years of age)
• refers to a group of syndromes caused by different mechanisms all resulting in vascular lesions in the brain
• lesions can be the result of diffuse cerebrovascular disease or focal lesions (or a combination of both, which is what is observed in the majority of cases). (image)
• can be diagnosed as "mixed" dementia, when comorbid with Alzheimer's or other dementias (image)
• onset is often unnoticed, esp. if strokes are minor
  • symptoms (caused by each stroke) may include transient mild weakness in the limbs, slurred speech, dizziness and a slight impairment to the short-term memory
  • cumulative effects of these strokes will eventually result in noticeable symptoms: recent memory, wandering or getting lost in familiar places, walking with rapid, shuffling steps, loss of bladder or bowel control, emotional lability, difficulty following instructions, problems handling money
• second most common cause of dementia in the United States and Europe in the elderly, most common form in some parts of Asia
• prevalence is 1.5% in Western countries, higher in men than in women, and increases with age. (graph)
• In small vessel disease the incidence peaks between the 4th and the 7th decades of life and 80% will have a history of hypertension.
  • Patients develop progressive cognitive, motor and behavioural signs and symptoms.
  • A significant proportion also develop affective symptoms.
  • These changes occur over a period of 5-10 years.
  • If the frontal lobes are affected (which they very often are) patients may present as apathetic or abulic (loss or impairment of the ability to make decisions or act independently), and often accompanied by problems with attention, orientation and urinary incontinence.
• The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls.
• Vascular dementia is associated with a higher mortality than 'Alzheimer's', presumably because of the excess in cardiovascular risk factors.
• Diagnosis:
  • On cognitive testing patients have patchy deficits:
    1. They tend to have better free recall and fewer recall intrusions compared with patients with Alzheimer's disease.
    2. As small vessel disease often affects the frontal lobes, apathy early in the disease is more suggestive of vascular dementia because it usually occurs in the later stages of 'Alzheimer's'.
    3. patients with vascular dementia perform worse than their Alzheimer's disease counterparts in frontal lobe tasks such as verbal fluency.
    4. patients with vascular dementia also tend to exhibit more perseverative behaviour.
    5. patients with vascular dementia may also present with general slowing of processing ability, difficulty shifting sets and impairment in abstract thinking.
    6. In the more severe patients or those patients affected by strategic infarcts in the Wernicke or Broca areas; dysarthrias, dysphasias and aphasias may be present.
• Risk factors for vascular dementia include hypertension, smoking, hypercholesterolemia, diabetes mellitus, and cardiovascular and cerebrovascular disease.
• The aim of treatment is the prevention of further cerebrovascular lesions. This includes administering antiplatelet drugs and controlling major vascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus to mention a few).

Dementia with Lewy Bodies

• second most frequent cause of hospitalization for dementia, after Alzheimer's disease.
• Current estimates are that about 60-to-75% of diagnosed dementias are of the Alzheimer's and mixed (Alzheimer's and vascular dementia) type, 10-to-15% are Lewy Bodies type,
• characterized by development of abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions, called Lewy bodies, throughout the brain: (images)
• these inclusions have similar structural features to "classical" Lewy Bodies seen subcortically in Parkinson's disease. Additionally, there is a loss of dopamine-producing neurons (in the substantia nigra) similar to that seen in Parkinson's disease, and a loss of acetylcholine-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer's disease. (Image)
• Cerebral atrophy (or shrinkage) also occurs as the cerebral cortex degenerates - autopsies have revealed that the pathology of DLB is often concomitant with the pathology of Alzheimer's diseas:
  • when Lewy Body inclusions are found in the cortex, they often co-occur with Alzheimer's disease pathology found primarily in the hippocampus, including: neurofibrillary tangles (abnormally phosphorylated tau protein), senile plaques (deposited beta-amyloid protein), and granulovacuolar degeneration.
• Symptoms/mechanisms:
  • loss of cholinergic (acetylcholine-producing) neurons is thought to account for the degradation of cognitive and emotional functioning as in Alzheimer's disease
  • the loss of dopaminergic (dopamine-producing) neurons is thought to account for the degradation of motor control as in Parkinson's disease
  • DLB is similar in some ways to both the dementia resulting from Alzheimer's disease and Parkinson's disease
  • is often confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia)
  • overlap of neuropathologies and presenting symptoms (cognitive, emotional, and motor) may make an accurate differential diagnosis difficult

    Core features include fluctuating cognition with variations in attention and alertness, recurrent visual hallucinations (typically early in the disease), and motor features of parkinsonism. DLB patients also often experience repeated falls, syncope (fainting), transient loss of consciousness, and hypersentivity to neuroleptic medications. Generally, DLB is diagnosed when cognitive symptoms develop within a year or two of movement disorder/Parkinsonian symptoms. Recent research suggests that presence of sleep disturbance may also be useful in differentiating DLB from other forms of dementia.

  • Treatment involves striking a balance between treating the motor and emotive/cognitive symptoms:
    • Treatment of the movement portion of the disease (dopaminergic) can typically result in worsening hallucinations and psychosis
    • treatment of the hallucinations and psychosis (anti-dopaminergic) can result in worsening movement symptoms
    • use of cholinesterase inhibitors represents the treatment of choice

  Creutzfeldt-Jakob disease (CJD)

  • CJD is a very rare and incurable degenerative neurological disorder that is ultimately fatal. (as well as bovine spongiform encephalopathy (BSE) commonly known as mad cow disease, chronic wasting disease (CWD) in elk and deer, and scrapie in sheep.)
  • the most common transmissible spongiform encephalopathy found in humans
  • caused by prions (short for proteinaceous infectious particle)
    • poorly-understood hypothetical infectious agents that, according to the "protein only" hypothesis, are composed entirely of proteins
    • affect the structure of the brain or other neural tissue
  • quite rare and only occurs in about one out of every one million people
  • usually affects people aged 45Ð75, most commonly appearing in people between the ages of 60Ð65. (image)
  • CJD can be fatal within months or even weeks. CDC: the duration of CJD is less than 1 year (median: 4 months) after onset of symptoms(image)
  • rapidly progressive dementia, leading to memory loss, personality changes and hallucinations.
  • accompanied by physical problems such as speech impairment, jerky movements (myoclonus), balance and coordination dysfunction (ataxia), changes in gait, rigid posture, and seizures.
  • caused by the progressive death of the brain's nerve cells, which is associated with the build-up of abnormal prion proteins.
  • When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died... 'spongiform' in refers to the 'spongy' appearance of the brain tissue
  • Diagnosis
    • EEG: often has characteristic "triphasic" spikes (blunted spike and wave" pattern - high-amplitude (>70 µV), positive sharp transients that are preceded and followed by negative waves of relatively lower amplitude. (image,another )
    • Cerebrospinal fluid analysis for 14-3-3 protein
    • MRI of the brain Ñ often shows high signal intensity in the Basal Ganglia (caudate nucleus and putamen) bilaterally on T2-weighted images. image, early/late, DWI)