Dementia and Delirium Flashcards
It is important to recognize that the signs and symptoms of dementia, delirium, and depression overlap considerably. It is extremely important to clarify which of these disorders your patient is suffering since treatment for depression and delirium are frequently effective while treatments for dementia are less commonly effective.
What is dementia?
Impairment of intellectual/cognitive function of sufficient severity to interfere with social or occupational activities.
What is delirium?
Clouding of consciousness (altered clarity of awareness of the environment), with reduced capacity to shift, focus, and sustain attention to environmental stimuli.
This slide presents the DSM IV diagnostic criteria for dementia. Remember, although there are DSM diagnostic criteria for dementia, dementia is not a disease, it is a symptom.
- Impaired short-and long-term memory.
and/or
- At least one of the following:
a. Impaired abstract thinking.
b. Impaired judgment.
c. Other disturbance e.g., aphasia, apraxia, agnosia.
3. Disturbances in 1. or 2. interferes with work or ADL.
4. Symptoms not occurring exclusively during delirium.
- Either:
a. evidence from hx, physical exam or laboratory of organic cause.
b. in the absence of evidence for organic cause, exclusion of non-organic mental disorder, e.g., depression.
DSM-5 changes to dementia
In DSM-5, dementia gets a new name: Major Neurocognitive Disorder, but the term dementia will still be frequently used. It is not precluded from use in the etiological subtypes where that term is standard such as HIV associated dementia.
Dementia as a Major Neurocognitive Disorder includes:
Alzheimer disease, cerebrovascular disease that causes vascular dementia, frontotemporal lobar degeneration, Lewy Body disease, Huntington’s disease, traumatic brain injury and HIV associated dementia.
More DSM-5 changes to dementia
The Task Force also removed the subcategories ‘With Early Onset’ (onset at age 65 years or below) and ‘With Late Onset’ stating that “there is little scientific rationale for retaining the distinction between early and late onset, as the underlying pathology is the same, and the threshold of age 65 is arbitrary at best.”
Another change is that memory impairment will not be a mandatory requirement for classification, as dementia can be diagnosed in the absence of memory impairment if other areas of cognitive function are impaired.
DSM-5 now recognizes a less severe level of cognitive impairment, called:
mild NCD, which is a new disorder that permits the diagnosis of less disabling syndromes that may nonetheless be the focus of concern and treatment. Diagnostic criteria are provided for both major NCD and mild NCD, followed by diagnostic criteria for the different etiological subtypes.
DSM- IV criteria for diagnosis of delirium
- Disorientation and memory impairment (if testable).
- At least two of the following:
a. Perceptual disturbance: misinterpretations, illusions, or hallucinations
b. Speech that is at times incoherent
c. Disturbance of sleep-wakefulness cycle, with insomnia or daytime drowsiness
d. Increased or decreased psychomotor activity - Clinical features that develop over a short period, usually hours or days, and that tend to fluctuate.
- Evidence from the history, physical examination, or laboratory tests, of a specific organic factor judged to be etiologically related to the disturbance.
Similarly, DSM5 criteria for delirium will change too to include:
There is a disturbance in attention with reduced ability to direct, focus, sustain, and shift attention and there is a lack of awareness that anything is wrong.
There is a change in cognition such as memory deficit, disorientation, language disturbance, perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia.
The disturbance develops over a short period of time, usually hours to days, and tends to fluctuate during the course of the day.
The history, physical exam and/or laboratory findings indicate that the disturbance is caused by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause.
What are the major causes of dementia?
• Neurodegenerative Diseases
Alzheimer’s Disease (50-60%), Dementia with Lewy Bodies (10-15%), Frontotemporal Dementia (Pick’s Disease), Parkinson’s Disease, Huntington’s Disease, Wilson’s Disease, Multisystem Degenerations, Amyotrophic Lateral Sclerosis, Spinocerebellar Degenerations
- Vascular Dementia (10-20%)
- Head Trauma (1-5%)
- Drugs, Toxins, Ethanol (1-5%)
- Brain Tumors (1-5%)
Other causes of dementia
• Normal Pressure Hydrocephalus (1-5%)
• Infections: Creutzfeldt-Jakob Disease, AIDS, Neurosyphilis, Viral/Fungal/Bacterial Meningoencephalitis, Progressive Multifocal Leukoencephalopathy, Whipple’s Disease
• Metabolic Disorders: Hypo/Hyperthyroidism, Liver/Renal Disease, Cushing’s Disease
• Nutritional: B1, B12, Folate, Niacin Deficiencies
Describe Alzheimer’s Disease
A progressive neurodegenerative dementing disorder characterized by the neuropathological findings of:
Ø Loss of cerebral cortical neurons
Ø Neuritic plaques containing β-amyloid
Ø Neurofibrillary tangles
What are the essential critieria for Alzheimer diagnosis?
- Dementia confirmed by neuropsychological tests
- Deficits in memory plus one or more areas of cognition
- Progressive worsening of memory plus one other cognitive function
- No disturbances of consciousness
- Onset between ages 40 to 90; most after 65
- Absence of other brain disease to explain dementia
What are the supporting critieria for Alzheimer diagnosis?
- Progressive deterioration of single cognitive area
- Impaired activities of daily living, altered behavior
- Family history of dementia
- Laboratory showing normal CSF, nonspecific EEG, and atrophy on CT or MRI
NOTE: The absolute diagnosis of Alzheimer’s disease remains a post-mortem, pathological diagnosis despite several laboratory-based tests touted as methods for a definitive pre-mortem diagnosis.
What are the consistent features for diagnsosis of Alzheimer’s?
- Plateaus in course
- Associated depression, insomnia, incontinence, delusions
- Non-specific neurological findings later in disease, e.g., altered muscle tone, myoclonus, gait ataxia, seizures
- CT or MRI ‘normal for age’
What are the inconsistent features for diagnsosis of Alzheimer’s?
- Sudden or acute onset
- Focal neurologic findings, e.g., hemiparesis etc.
- Seizures or gait disorder at onset or early in disease
How common is Alzheimer’s?
- ~ 500,000 new cases in U.S. each year
- 5 – 10% of population >65 yr. and 40 – 45% >85 yr. will develop Alzheimer’s Disease
- ~ 5.4 million people with Alzheimer’s in U.S.
- These numbers are expected to triple over the next 10 – 20 years as the ‘baby boom’ population enters their 7th and 8th decades
This slide presents the normalized prevalence of cognitive disorders versus age. Past age 65 there is a marked increase in the incidence of cognitive disorders, the great majority of which are Alzheimer’s disease. It is now estimated that nearly 50% of individuals reaching age 90 will have some form of cognitive disorder and again most of these will be patients with Alzheimer’s disease.
Alzheimer’s disease is the most common cause of dementia among older adults. The pathogenesis is thought to be:
the production and accumulation of beta-amyloid peptide, bringing about the formation of neurofibrillary tangles, oxidation and lipid peroxidation, glutamatergic excitotoxicity, inflammation, and activation of the cascade of apoptotic cell death.
A less favored but still tenable hypothesis for the cause of Alzheimer stresses:
tau-protein accumulation, heavy metals, vascular factors, and viral infections.
How does Alzheimer disease present?
The natural course of AD averages 10 years. The cardinal features are insidious onset, progressive course, and early memory loss; at least one other cognitive impairment such as language dysfunction, apraxia, agnosia, visuospatial disorder, as well as executive dysfunction, must be seen. These impairments should constitute a decline from the previous level of cognitive functioning, interfering with daily activities.
_______ ______is the hallmark of cognitive change in AD.
Memory decline. It is characterized as a storage deficit, meaning that information cannot be recalled with cue.
T or F. In the early stage of AD, memory impairment for recent events is common whereas long-term memory remains intact.
T. As the disease progresses, individuals with AD are increasingly unable to recall more distant memories.
More on the presentation of AD
Typically, the motor signs are absent early in the course. Likewise, sensory abnormalities, seizures, and gait difficulties are uncommon until the late phase of disease.
Behavioral changes, including depression, anxiety, apathy, aggression, agitation, wandering, vocalization, disinhibition, and abnormal eating, are common thereafter and cause caregiver stress as well as greater use of health care service.
Premorbid diagnosis is purely clinical, i.e. no definitive laboratory test.
•Postmortem diagnosis of AD is based on presence of histological evidence of:
a) neuritic plaques,
b) neurofibrillary tangles, and
c) neuron loss.
This slide presents the gross pathology seen in Alzheimer’s disease. Note the profound parietal atrophy, dorsal frontal temporal lobe atrophy, and the somewhat less severe frontal pole atrophy. The atrophy is manifested by narrowing of the gyri and associated widening of the sulci.
What is this?
This slide presents a silver stain (Bielschowsky stain) of human cortex from an Alzheimer’s disease patient. The neuritic plaque labeled NP in the center of the slide is composed of dystrophic neurites or synapses containing tau protein aggregates surrounding a core of aggregated beta-amyloid. Neurofibrillary tangles labeled NFTs are cortical pyramidal cells filled with aggregated tau protein that has been hyperphosphorylated.
This slide is another example of neuritic plaques in the neocortex and neurofibrillary tangles in the hippocampus.
This slide presents a color depiction of the distribution of plaques with increasing density from dark green up through light green to yellow.
Note the highest density of tangles differs from that of plaques with the parietal lobe have fewer tangles than plaques.
Table: percent distribution of the three alleles in a normal control population and in a population of autopsy proven cases of Alzheimer’s disease. Note the disproportionate occurrence of APOE4 in individuals with Alzheimer’s disease.
This slide presents a Kaplan-Meier curve with the vertical axis showing the number of patients remaining unaffected by Alzheimer’s disease versus their age on the horizontal axis. The genotype of each population is shown in different colors with homozygotes for APOE4 (E4/E4) shown in yellow, heterozygotes for APOE4 in gold and green, and so on.
This slide shows normal APP in the upper figure. What is APP?
APP is a cell membrane bound protein with its N-terminal end within the cytoplasm and the C-terminal end lying outside the cell. In this figure the cell membrane is shown as the wide blue line. Three membrane bound enzymes, alpha, beta, and gamma secretase cleave APP at different points and it’s the combination of beta and gamma secretase activity that results in a peptide fragment that is labeled Aβ and aggregates into beta-amyloid.
What are Presenilin 1 and 2?
membrane bound proteins that are associated as a complex with the secretase that cleave APP. Mutations in Presenilin 1 or 2 will cause Alzheimer’ disease in an autosomal dominant inheritance
This slide presents two anatomical diagrams showing an area of deep, midline brain that has important clinical applications for Alzheimer’s disease therapy. Neuroscientists noted years ago that the ________ ____ _______ became atrophied in Alzheimer’s patients.
nucleus basalis (of Meynert)
What does the nucleus basalis of Meynert do?
This nucleus harbors neurons that heavily innervate the neocortex using the neurotransmitter acetylcholine.
The figure in A depicts this cholinergic distribution from the nucleus basalis to neocortex as blue arrows. In accordance with these anatomical observations, neuroscientists have shown that the levels of acetylcholine in neocortex of humans with Alzheimer’s disease are significantly decreased. These observations lead to the first successful symptomatic (not curative) therapy for Alzheimer’s disease.
This slide presents a cholinergic synapse. Describe it
A synaptic bouton is depicted in light purple in the upper middle of the slide showing the synthesis of acetylcholine and its storage within vesicles waiting to be released into the synaptic cleft. The lower portion of the slide shows the post-synaptic membrane with a cholinergic receptor.
The enzyme, acetylcholine esterase (AChE) is shown in the synaptic space and attached the to postsynaptic membrane. AChE in this location is thus able to inactivate synaptic ACh and thus attenuate synaptic transmission.
Now, if a drug is given that blocks AChE function X, increased levels of ACh will develop and activation of post-synaptic neurons will increase.
How is immunotherapy used to tx AD?
Produce active immunization against β-amyloid or to use passive immunization by giving synthetic antibodies to patients with Alzheimer’s disease to bind to AB deposits
immunotherapy aimed at clearing β-amyloid from the brain has shown some promise as a treatment to slow down the progression of Alzheimer’s disease.
This slide is to emphasize that there are other symptoms of Alzheimer’s disease including depression, anxiety, delusions, and insomnia that can be treated.
How does Pick’s Disease present?
Clinically these individuals present with a progressive loss of frontal lobe executive type functions, i.e. loss of judgement, disinhibition, social and sexual misconduct.
These cognitive defects appear out of proportion to the loss of memory that is more typical for Alzheimer’s disease. If the temporal lobe is primarily involved then there is an early loss of receptive language function.
This slide nicely shows the marked frontal lobe and anterior temporal lobe atrophy with relative sparing of the parietal lobe in Pick’s Disease
