delirium,alzheimer'sdisease,andotherdementias

Delirium

Acute confusional state characterized by disturbances of consciousness and changes in cognition, including severe confusion, which develop over a short period of time

The most important aspect in the diagnosis of delirium

is differentiating it from dementia (or other conditions)

Delirium can often be

stopped or cured

Latin origin of delirium

From the Latin delirare, “being deranged”, “madness”

Delirium can be caused by

any number of conditions, including:

• Stroke

• Cardiovascular disease

• Metabolic conditions

• Dehydration

• Fever

• Medication side effects

• Substance intoxication or withdraal

• Exposure to toxins

• Combination of factors

Dementia literally means

losing one’s mind

Dementia is characterized by

cognitive and behavioral deficits involving some form of permanent brain damage

Dementia is

progressive brain degenerative disorder

Dementia is not a single disease

but a cluster of conditions

The amount of types of dementia that has been identified is

about a dozen

The amount of people affected by dementia

is about 45%

Dementia and older adults percentage

• At age of 65 the rate i less than 1%

• For those over 85 the rate increases to about 50%

Types of dementia

• Dementia with Lewy Bodies (LBD)

• Fronto-temporal Dementia (FTD)

  • Several variants, including Pick’s Disease

• Creutzfeldt-Jakon Disease (CJD)

• Wernicke-Korsakoff Syndrome

• AIDS Dementia Complex or HIV-Associated Dementia

• Cerebrovascular (or vascular) Dementia

• Alzheimer’s Disease (AD)

  • (DAT, SDAT, Senile Dementia of the Alzheumer Type)

• Mixed Dementia

Dementia with Lewy Bodies (LBD)

Motor degenerative disorders leading to dementia (related to PD)

Fronto-temporal Dementia (FTD)

Early onset, characterized by changes in personality and emotion

Creutzfeldt-Jakob Disease

Rare, invariably fatal brain disorder; onset of symptoms occurs at about age 60

Wernicke-Korsakoff Syndrome

• Wernicke encephalopathy is acute

• Korsakoff’s syndrome is chronic

AIS Dementia Complex (ADC) or HIV-Associated Dementia (HAD)

• Encephalitis, behavioral changes, decline in cognitive function

• Progresive slowing of motor function

Cerbovascular (or vascular) Dementia

Numerous small cerebral vascular accidents

Alzheimer’s Disease

The most common form of progressive, degenerative, and fatal dementia accounting for as much as 70% of dementia cases

Dementia with Lewy Bodies symptoms

• Includes some of the symptoms common in AD

• Also initial or early symptoms such as sleep disturbances, well-formed visual hallucinations, and muscle rigidity or other PD-like movement problems

Lewy Bodies

Abnromal aggregations of the protein alpha-synuclein in the cortex

Alpha-synuclein

Also aggregates in the brains of people with PD, but the aggregates may appear in a pattwen that is different from dementia with Lewy bodies

Phineas Gage

Phineas Gage’s brain injury to the frontal lobe led to major personality changes, illustrating how frontal lobe damage, which is common in certain dementias like frontotemporal dementia, can impair judgement, behavior, and emotional regulation

Fronto-Temporal Dementia (FTD)

Rare syndrome caued by degeneration of the frontal loves an may extend to the temporal lobe

• Selective early loss of Von Economo Neurons (VENs)

FTD has both

• Sporadic variant: FTD arises without a known family histroy or identifible genetic cause

• Familial variant: FTD is inherited an runs in families due to genetic mutations

FTD vs AD

FTD has a earlier onset and shorter survival

FTD symptoms

• Changes in personality, judgement, and behavior

• Difficulty with language

• Lethargy, or, oppositely disinhibition

  • Apathetic patients may become socially withdrawn an stay in bed all day or no longer take care of themselves

  • Disinhibited patients can make inappropriate comments or peform inappropriate acts

• Patients become unable to perform skills that require complex planning or sequencing so problems ith executive function

Cretzfeld-Jakob Dementia (CJD)

Rapidly fatal wasting disorder that impairs memory and coordination and causes behavior changes

CJD brain changes

Infectious misfoled protein (prion) that causes other proteins throughout the brain to misfol and thus malfunction (spongiform brain appearance)

Comanility of CJD

Very rare as 1 million people per year worldwide are diagnosed

Causes of CJD

• Sporadic CJD: develops spontaneosuly for no known reason (85%)

• Familial CJD: dominant genetic changes inherited from an affected parent (14%)

• Infectious CJD: results from exposure to an external source of abnormal prion protein; the two most common outside sources are medical procedures and consumption of products from cattle affected by mad cow disease (1%)

Cerebrovascular Dementia (CSVD)

Brain injuries such as mini strokes and microscopic bleeding (lacunae) and the location of the injury determines how the individual’s thinking and physical functioning are affected

Mixed dementia

Pathologic evidence shows that the brain changes of both AD and CSVD are most often present simultaneously

CSVD risk factos

• Cardiovascular disease including high blood pressure

  • Recommended values <_ 120/80 mmHg

• Arteriosclerosis (arterial stiffening)

• Atheroscleroris (fat deposits in the arteries)

• Transient ischemic attacks (TIAs)

CSVD contributing causes

• Cerebral small vessel disease (CSVD)

• White matter dysfunction

Vital functions change with age

This is important because this influences on risk of AD

Cardiovascular system changes with age

With age there is accumulation of fat deposits an stiffening of heart muscles, valves, and arteries which can lead to arteriosclerosis and atherosclerosis

Measuring brain arterial stiffening optically

• Pulse oximetry

• Pulse-DOT in the brain

Cerebrovascular function and aging

Blood flow and tissue perfusion in the brain decrease with aging due to

• Hypertension and increased peripheral resistance

• Arteriosclerosis and plaque formation

• Decreased cardiovascular reactivity

Arterial elasiiticity in older adults

As people age, there is a loss of arterial elasticity which is noticeable in middle age

Which leads to a cascade of delayed effects including white matter abnormalities

Early classifications of dementia (historic)

• AD or pre-senile dementia

• Senile dementia

AD or pre-senile dementia (rare)

• Early onset

• Hereditary

• Hallmark microscopic signs: amyloid plaques and neurofibrallary tangles

Senile dementia

• Late onset

• Attribute to age-related wear and tear

• Closely linked to arterioclerosis

Hallmark changes in the brains of AD are

microscopic

• Therefore, AD could only be definitively diagnosed at autopsy

• New measures have changed that:

• Pittsburgh compound B (PiB) tracer to measure beta-amyloid (aka a-beta) deposition

• Lumbar puncture (and other assays) to assess tau

Characteristics for AD

• Most common form of dementia

• Progressive, degenerative, fatal

  • A person can live 3-20+ after onset

• Moderate to small dose response between a-beta and cognitive decline

• Typical and atypical presentations, progressions, and subtypes

2 types of AD

• Early-onset AD

• Late-onset AD

Early-onset AD

• Rare

• Autosomal dominant gene

• Mutations in the presenilin proteins (PSEN1, PSEN2) or the amyloid precurosr protein (APP)

• Majority of these cases carry mutant presenilin genes

Late-onset AD

Common

Many contributing risk factors including:

• Some genetic influences

• Link with obseity

• Beta-amyloid cascade hypothesis, leading to inflammation

• Chronic arthritis

• Dysfunction of BBB

• Links with bateria (like gum disease)

• Links with viral infections; protections from vaccines

• Vascular hypothesis

• Social isolation and loneliness

• Traumatic brain injury and repeated concussions

The thing that can diminish risks of AD is

lifestyle choices like fitness, nutrition, use of certain medications, avoiding head traumas

Neural changes in AD

• Neurofibrillary tangles

• Beta amyloid plaques

• Cell death

• Decreases in certain neurochemicals

• Hippocampus and ventricle shrink

Neurofibrillary tangles

• Accumulations of pairs of filaments in the neuron that become wrapped around each other

• Microtubules are part of the neuron’s support system and are bound by the tau protein

• During AD there is alteration the quantity and type of tau produced

Beta amyloid plaques

• Spherical structures consisting of a core of beta-amyloid surrounded by degenerated fragments of dying or dead neurons

• Amyloid-beta precursor protein plays an essential role in neural growth and repair, but it can break down into toxic fragments

• Beta-amyloid plaques are typically surrounded by neurons containing neurofibrillary tangles

• Believed to cause vascular damage and neuronal cell loss

• Also found in the brain of the average healthy older individual

Cell death

Occurs in the hippocampus, the cortex, and the basal forebrain

Decreases in certain neurochemicals

• Particularly acetylcholine

• Increased levels of plasma homocysteon