✅ Dementia / Delerium (Confusional State) Flashcards
Delirium
An acute state of confusion and may be either 😴 hypoactive, with a depressed level of consciousness, or 😃 hyperactive, with an increased level of alertness.
Syndrome characterized by “altered mental status (AMS)” with a wide range of potential neuropsychiatric manifestations:
- The clinical hallmark is inattention (loss of concentration) and a fluctuating course.
- Agitation may compromise safety and interfere with medical management (eg, difficulty with intravenous fluid or antibiotic administration, radiologic testing).
Tx: The treatment of choice for agitation in the elderly is low-dose haloperidol.
Tx: Atypical antipsychotics (quetiapine, risperidone) may also be used. Usage of typical and atypical antipsychotics is safe in the acute setting, but prolonged use can increase mortality in the elderly. Typical antipsychotics should not be used in patients with Lewy body dementia, who may exhibit neuroleptic hypersensitivity (severe parkinsonism and impaired consciousness with neuroleptic administration).
Dementia
Impairment of 🧩 memory and at least one other cognitive function (e.g., language, visual-spatial orientation, judgement) WITHOUT alteration in consciousness; representing a decline from previous level of ability, and interfering with daily functioning and independent living.
Mild Cognitive Impairment (MCI)
A loss of cognitive ability that exceeds the expected age-related memory loss but does not interfere significantly with daily activities. The term is sometimes used to describe the early phase of cognitive decline observed in patients who later receive a diagnosis of Alzheimer disease.
There are universal age-related declines in cognition that chiefly affect memory, learning, and problem solving beginning around age 40 years, and these changes may be noticeable to patients.
Alzheimer Disease (AD)
Most common cause of dementia (60%-80% of cases). The result of structural neuronal changes with pathologic features including deposition of insoluble, neurotoxic β-amyloid protein in extracellular parenchymal plaques and intracellular accumulation of neurofibrillary tangles composed of abnormal tau protein.
Early Manifestations: Impairment of recent memory is typically the first sign of Alzheimer disease and may be noticed only by family members. As the memory disorder progresses over months to several years, the patient becomes disoriented to time and then to place. Aphasia, anomia, and acalculia may develop, forcing the patient to leave work or give up the management of family finances.
The depression apparent in the earlier stages of the disorder may give way to an agitated, restless state. Apraxias and visuospatial disorientation ensue, causing the patient to become lost easily. Primitive reflexes are commonly found. A frontal lobe gait disorder may become apparent, with short, slow, shuffling steps, flexed posture, wide base, and difficulty in initiating walking.
The language disturbance may take the form of decreased fluency, dysnomia, and transcortical sensory aphasia, which refers to a reduction in the ability to understand complex linguistic structures.
Late Manifestations: Late manifestations—In the late stages, previously preserved social graces are lost, and psychiatric symptoms, including psychosis with paranoia, hallucinations, or delusions, may be prominent. Seizures occur in some cases. Examination at this stage may show rigidity and bradykinesia. Rare and usually late features of the disease include myoclonus, incontinence, spasticity, extensor plantar responses, and hemiparesis. Mutism, incontinence, and a bedridden state are terminal manifestations.
Hereditary Alzheimer disease which appears between the ages of 40 and 50, the presenilin 1 gene, located on chromosome 14, is involved in 70% to 80% of cases. Another 20% to 30% are attributable to the presenilin 2 gene, located on chromosome 1, responsible for hereditable cases of Alzheimer disease appearing at age 50. A final 2% to 3% of Alzheimer cases, which appear after the age of 50, are attributable to the β-amyloid precursor protein (APP) gene located on chromosome 21.
Dx: CT scan or MRI often shows temporal and parietal (especially medial temporal lobe) atrophy and enlarged ventricles, but such changes are nonspecific.
Tx: Cholinesterase inhibitor donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon). They are associated with modest improvements in cognition, behavior, activities of daily living, and global measurements of functioning. However, they do not change the progression of neurodegeneration.
N-methyl-D-aspartate receptor antagonist (memantine) is the only drug approved by the Food and Drug Administration as first-line treatment of moderate to advanced Alzheimer disease.
Non pharmacologic: Cognitive stimulation included a range of activities designed to stimulate thinking, concentration, and memory. Cognitive stimulation was associated with improved cognitive function immediately after treatment. Quality of life also improved, but there was no impact on mood, overall functional level, or caregiver outcomes.
Frontotemporal (Pick) dementia
📈 Progressive neuropsychiatric disorder characterized by early behavioral and personality changes that range from apathy to social disinhibition. Patients may fail to change their clothes, brush their teeth, pursue their former interests, or initiate many of their previous activities that constituted a normal day. They may fixate, in a seemingly idiosyncratic fashion, on a particular activity, such as going to the bathroom, sorting through a wallet, hoarding magazines, or watching television. Some patients have greater disinhibition and emotional lability (crying or laughing inappropriately).
Behavioral changes often precede memory impairments (in contrast to AD).
Dx: Disproportionate atrophy of the frontal and anterior temporal brain regions.
Lewy Body Dementia
Dementia with Lewy bodies (DLB) presents with dementia plus ≥2 of the following features: 😵 Visual hallucinations, ⚙ parkinsonism, fluctuating cognition, and REM sleep behavior disorder. Tx: DLB include carbidopa-levodopa for parkinsonism, cholinesterase inhibitors (eg, rivastigmine) for cognitive impairment, and melatonin for REM sleep behavior disorder. A trial of an antipsychotic medication (eg, risperidone) may be indicated in patients with functionally impairing visual hallucinations or delusions, but it must be prescribed with caution due to the extreme antipsychotic hypersensitivity of patients with DLB. Antipsychotics may be associated with worsening confusion, parkinsonism, and autonomic dysfunction when used in such patients.
Characterized by parkinsonism that is responsive to dopaminergic therapy, visual hallucinations, and/or fluctuating cognition. The characteristic cognitive profile of dementia in patients with dementia with Lewy bodies includes impaired learning and attention, psychomotor slowing, constructional apraxia, and more profound visuospatial impairment but less memory impairment than in similarly staged patients with Alzheimer disease.
Dx: Intraneuronal Lewy body inclusions in the cerebral cortex.
Tx: Responds to cholinesterase inhibitors.
Patients with dementia with Lewy bodies (DLB) are extremely sensitive to antipsychotics, and use of this class of medication may be associated with worsening confusion, parkinsonism, and autonomic dysfunction. If DLB-associated psychotic symptoms are functionally impairing, a trial of a low-potency second-generation antipsychotic (eg, quetiapine) may be cautiously undertaken.
Vascular Dementia
Consequence of progressive ischemic brain injury; stepwise deterioration; early executive dysfunction.
Dx: Patients with this diagnosis may have multiple large (>1 cm in diameter) cortical infarcts; strategic infarcts involving hippocampus or thalamus; multiple small (eg, lacunar) infarcts affecting subcortical white matter, basal ganglia, or thalamus; diffuse ischemic lesions of subcortical white matter (Binswanger disease); intracerebral hemorrhages (eg, cerebral amyloid angiopathy); or combinations of these.
Px: The neurologic examination may show pseudobulbar palsy with dysarthria, dysphagia, and pathologic emotionality (pseudobulbar affect); focal motor and sensory deficits; ataxia; gait apraxia; hyperreflexia; and extensor plantar responses.
Normal pressure hydrocephalus (NPH)
A potentially reversible cause of dementia, is characterized by the clinical triad of dementia, gait apraxia, and incontinence. The dementia is often mild and insidious in onset and is typically preceded by gait disorder and incontinence. It is characterized initially by mental slowness and apathy and later by global cognitive dysfunction.
Sometimes called communicating hydrocephalus (because the lateral, third, and fourth ventricles remain in communication) or nonobstructive hydrocephalus (because the flow of CSF between the ventricles is not impaired). It is presumed to be caused by impaired CSF absorption from arachnoid granulations in the subarachnoid space over the cerebral hemispheres.
In contrast, noncommunicating or obstructive hydrocephalus is caused by a blockade of CSF circulation within the ventricular system (eg, by an intraventricular cyst or tumor) and is associated with increased CSF pressure and often with headache and papilledema.
Urinary incontinence is a later development, and patients may be unaware of it; fecal incontinence is uncommon.
Gait apraxia: Characterized by unsteadiness on standing and difficulty in initiating walking (magnetic gait), even though there is no weakness or ataxia. The patient can perform the leg movements associated with walking, bicycling, or kicking a ball and can trace figures with the feet while lying or sitting but is unable to do so with the legs bearing weight. The patient typically appears to be glued to the floor; walking, once underway, is slow and shuffling.
Dementia is manifested by psychomotor slowing, inattention, and impaired decision making and spatial recognition. Urinary incontinence is a later development, and patients may be unaware of it; fecal incontinence is uncommon.
Dx: The CSF in patients with NPH is typically normal. Lumbar puncture reveals normal or low opening pressure and is both diagnostic and theraputic.
Tx: LP; Ventriculoatrial, ventriculoperitoneal, or lumboperitoneal shunting.
Wernicke encephalopathy
Wernicke encephalopathy is usually a complication of chronic alcoholism, but it also occurs in other disorders associated with malnutrition, such as anorexia nervosa, cancer, and after bariatric surgery. It is caused by deficiency of thiamine (vitamin B1).
Px: The classic syndrome comprises the triad of ophthalmoplegia, ataxia, and confusional state. The most common ocular abnormalities: nystagmus, abducens (VI) nerve palsy, and horizontal or combined horizontal–vertical gaze palsy. Ataxia affects gait primarily; ataxia of the arms is uncommon, as is dysarthria. The mental status examination reveals global confusion with a prominent disorder of immediate recall and recent memory. Most patients have associated neuropathy with absent ankle jerks. Hypothermia and hypotension may occur. Pupillary abnormalities, including mild anisocoria, or a sluggish reaction to light, are occasionally seen.
Dx: The peripheral blood smear may show macrocytic anemia, and MRI may show atrophy of the mammillary bodies.
Creutzfeldt-Jakob disease
This prion disease may be accompanied by parkinsonian features, but dementia is usually present, myoclonic jerks are common, and ataxia is sometimes prominent; there may be pyramidal or cerebellar signs and 👁 visual disturbances.
- Patients may have ataxia, clumsiness, or dysarthria, as well as diplopia, distorted vision, blurred vision, field defects, changes in color perception, and visual agnosia. Ultimately, cortical blindness may
occur. - Stimulus-sensitive, such that loud noises may provoke them.
Dx: The diagnosis may be supported by the finding of 〰 periodic sharp waves at a 1- to 2-Hz frequency on 📺 EEG and the finding of elevated protein 14-3-3 in CSF
Huntington disease
Huntington disease is a hereditary, progressive neurodegenerative disorder of the nervous system characterized by the gradual onset and subsequent progression of chorea and dementia.
- Characterized by increasingly severe motor impairment, cognitive decline, and psychiatric symptoms.
- Constant and fluid limb movements (chorea)
- Other motor symptoms include ataxia, dystonia, slurred speech, impaired swallowing, and myoclonus.
- Various psychiatric symptoms, such as dysphoria, agitation, irritability, anxiety, apathy, disinhibition, delusions, and hallucinations, commonly occur.
Deficits in sustained attention, memory retrieval, procedural memory (ability to acquire new skills), and visuospatial skills are predominant and early manifestations of the disorder. Language skills are usually preserved until the late stages of the disease. Personality changes and mood disturbances, including depression and mania, are frequent and can predate the onset of the dementia and the movement disorder.
Dx: CT scanning or MRI often demonstrates atrophy of the cerebral cortex and caudate nucleus in established cases. Reduction in striatal metabolic rate may be demonstrated
by PET.
Tx: Dopamine blocking and depleting agents are effective in decreasing the involuntary movements of HD. Haloperidol is a dopamine receptor blocker and is commonly used for control of chorea in HD. Other neuroleptics, such as olanzapine, risperidone, and aripiprazole, are also effective in treating the chorea symptoms of HD.
Inflammatory and autoimmune
SLE, CNS vasculitis, sarcoidosis, granulomatosis with polyangiitis, paraneoplastic disease
Nutritional (B12 and Wernicke)
Vitamin B12 deficiency
Vitamin B12 (**cyanocobalamin**) deficiency produces polyneuropathy, subacute **combined degeneration** of the spinal cord (combined systems disease) affecting the **cor**_t_**icos**_p_**inal tracts and dorsal columns**, nutritional amblyopia (visual loss), and cognitive dysfunction that ranges from a mild confusional state to dementia or psychosis (megaloblastic madness). The most frequent cause of vitamin B12 deficiency is **pernicious anemia**, a defect in the production of intrinsic factor associated with atrophic gastritis, anti-parietal cell antibodies, and achlorhydria. Other causes include gastric resection and vegan diet.
Hx: The presentation is usually with anemia or orthostatic lightheadedness but may also be neurologic. Distal paresthesias, gait ataxia, a bandlike sensation of tightness around the trunk or limbs, and Lhermitte sign (an electric shock–like sensation along the spine precipitated by neck flexion) may be present.
Px: Physical examination may show low-grade fever, glossitis (beefy red tongue), lemon-yellow discoloration of the skin, and cutaneous hyperpigmentation. Cerebral involvement produces confusion, depression, agitation, or psychosis with hallucinations. Spinal cord involvement causes impaired vibratory and joint position sense, sensory gait ataxia, ataxic heel-knee-shin and spastic paraparesis with extensor plantar responses. Associated peripheral nerve involvement may lead to loss of tendon reflexes in the legs and urinary retention.
Dx: Because folate deficiency can produce identical changes, the diagnosis
must be confirmed by measuring the serum vitamin B12 level. When this is low (<100 pg/mL), a Schilling test can determine whether defective intestinal absorption of vitamin B12 (as in pernicious anemia) is the cause, but the test is now rarely used. Diagnosis may be difficult when cerebral symptoms occur without anemia or spinal cord disease, so the serum vitamin B12 level should be determined routinely in patients with cognitive disorders, myelopathy, or peripheral neuropathy, regardless of whether
anemia is present.
Tx: Treatment of neurologic manifestations is by prompt intramuscular
administration of cyanocobalamin (1,000 μg), as soon as blood is drawn to determine the serum vitamin B12 level. Daily injections are continued for 1 week, and further testing is performed to determine the cause of deficiency. If, as in pernicious anemia, deficiency is not correctable by
dietary supplementation or treatment of an underlying cause (eg, intestinal malabsorption), intramuscular vitamin B12 (typically 1,000 μg) is given at weekly intervals for several months and monthly thereafter.
Wernicke Encephalopathy
Is caused by deficiency of thiamine (vitamin B1). Wernicke encephalopathy is usually a complication of chronic alcoholism, but it also occurs in other disorders associated with malnutrition, such as cancer, and after bariatric surgery. Pathologic features include neuronal loss, demyelination, and gliosis in periventricular gray matter. Proliferation of small blood vessels and petechial hemorrhages may be seen. The areas most commonly involved are the medial thalamus, mammillary bodies, periaqueductal gray matter, cerebellar vermis, and oculomotor, abducens, and vestibular nuclei.
The classic syndrome comprises the triad of ophthalmoplegia, ataxia, and confusional state.
The mental status examination reveals global confusion with a prominent disorder of immediate recall and recent memory.
Tx: Treatment is prompt administration of thiamine. An initial dose of 500 mg is given intravenously, before or with dextrose (which might otherwise precipitate or exacerbate the disorder).
Infectious
Brain abscess, chronic meningitis, HIV, CNS Whipple disease, syphilis, viral encephalitis (CMV, HSV)
Endocrine
🎀 Hypothyroidism in adults may present with headache, dementia, psychosis, and decreased consciousness. Neuromuscular findings are also common, and they include a myopathic weakness and a delay in the relaxation phase of reflexes (the hung-up reflex). Percussion of muscles may also cause a mounding of the muscle, called myoedema. Cerebellar ataxia may also occur. In severe cases,
myxedema coma may occur, characterized by hypothermia, hypotension, and respiratory and metabolic disturbances. This requires emergent replacement of thyroid hormone.
Hyperthyroidism
Hypoparathyroidism
