Dementia

slow processing

• tau inclusions
• either tau or TDP-43
• FUS accumulations are less common

a nonspecific finding in various central nervous system infectious and inflammatory conditions

• high-dose IV corticosteroid treatment
• usually the first step in acute therapy
• Azathioprine, mycophenolate mofetil, and rituximab may eventually be used in the chronic therapy regimen

• cardiomyopathy
•    present in mitochondrial disease
•    absent in J-C disease
• both have:
•    acute dementia
•    visual symptoms
•    extrapyramidal symptoms
•    positive family history
• MRI may not be useful

• key features:
•    fluctuations of cognition
•    visual hallucinations
•    longstanding sleep behavior suggestive of premorbid rapid eye movement (REM) sleep behavior disorder
• occipital hypometabolism in FDG-PET
• early in the course of dementia with Lewy bodies, problems with attention, executive function, and visuospatial skills usually dominate

• delayed recall
• in early Alzheimer disease, episodic memory is the predominant impaired domain, which would most commonly be tested with delayed recall of three words after a brief time delay

• susceptibility-weighted imaging (SWI)
• single lobar, cortical, or cortico-subcortical hemorrhage and focal or disseminated superficial siderosis satisfies the modified Boston criteria for probable cerebral amyloid angiopathy

• feature that distinguishes MCI from dementia is that the patient’s daily function is impaired in dementia but spared in MCI
• regularly forgets the names of casual acquaintances can still function in daily life, whereas people who frequently get lost when driving to work, have difficulty dressing, or are unable to manage personal finances or operate home appliances have functional deficits that are too great to be consistent with MCI

• reduced dopamine transporter levels on single-photon emission computed tomography (SPECT) scan
• typical of both dementia with Lewy bodies and Parkinson disease
• 90-100% specificity for differentiating these conditions from Alzheimer disease

• hippocampal atrophy on MRI scan
• increased spinal fluid levels of tau protein
• temporoparietal hypometabolism on FDG-PET scan

• a stereotyped disorder that often evolves in stages
• starting with headache, fever, or nausea
• then prominent psychiatric symptoms and behavioral changes including social withdrawal and stereotyped behavior
• eventually reduced responsiveness

• autosomal recessive
• arylsulfatase A deficiency
• adult-onset cases present with:
•    slow-onset psychiatric, behavioral, and cognitive changes
•    spasticity or peripheral neuropathy
• cholecystitis is an important non-neurologic manifestation
• MRI findings are typical of most leukodystrophies with bilateral symmetrical T2 changes in the white matter, usually more frontally located

• X-linked
• a mutation in the ABCD1 gene
• rapidly progressive white matter syndrome manifesting with parieto-occipital involvement on imaging
• cognitive impairment with visual processing disturbances as well as seizures and spastic paraparesis
• not expected to cause high degree of impairment in females
• cannot be transmitted to a male by his father
• 90% have associated adrenal insufficiency

• autosomal recessive
• rarely presents in adulthood
• when it does, cognitive and psychiatric symptoms appear later

• autosomal dominant
• presents with bulbar dysfunction in adults
• ataxia, spasticity, ocular motility disturbances, palatal myoclonus, and sleep disturbance
• toxic gain of function mutation in the GFAP gene
• MRI features are different than other leukodystrophies, with adult forms demonstrating medullary atrophy and changes in the dentate nuclei and middle cerebellar peduncles

• episodic memory
• specifically for recent events
• lose objects and repeat questions in a conversation
• procedural memory for task performance becomes impaired later
• working memory and semantic memory are often preserved until late in the disease course

• autosomal recessive
• mutations in the gene for mitochondrial sterol 27-hydroxylase
• tendon xanthomas (especially in the Achilles tendon)
• patients present with early psychiatric manifestations and later develop neurologic manifestations such as ataxia and upper motor neuron signs
• palatal myoclonus
• dentate nucleus changes
• white matter changes
• psychiatric and cognitive manifestations
• juvenile cataracts
• treatment with chenodeoxycholic acid may prevent neurologic deterioration

• a gait disorder that can include a variety of parkinsonian features, such as difficulty initiating gait, shuffling, tripping, falling, festination, retropulsion, anteropulsion, or difficulty with turns
• gait deficits are nearly universal among patients with idiopathic normal pressure hydrocephalus
• cognitive deficits and problems with sphincter control are less consistently present

progressive behavioral syndrome manifested by disinhibition

• neurodegenerative pattern of progressive language impairment
• losing the meaning of speech
• difficulty assigning meanings to words, specifically demonstrating impaired single-word comprehension
• dominant temporal lobe atrophy is also supportive

• the problem is more in expressive speech than understanding the content of speech
• She called a hammock ‘‘the...um...you know...between trees...rest.’’

multiple vascular risk factors, relatively greater impairment in executive function and processing speed than in episodic memory, reflex asymmetry, and neuroimaging findings suggestive of multiple small infarcts

• medial temporal lobe atrophy on MRI
• temporoparietal hypometabolism on FDG-PET
• diffuse uptake on amyloid positron emission tomography (PET)
• low levels of amyloid-β42 (Aβ42) in CSF (amyloid is deposited in brain tissue)
• high levels of tau protein (both t-tau and p-tau) in CSF (degeneration of tau-containing neurons)
• presence of the (APOE)ε4 haplotype

• rapidly progressive dementia
• confusion and memory loss as well as seizures, gait instability, headaches, or focal neurologic deficits
• MRI demonstrates white matter hyperintensities and enlarged blood vessels over the surface of the cortex
• diagnosis can be confirmed with cerebral angiography

• small cell lung carcinoma
• 90% of patients with limbic encephalitis and ANNA-1 (anti-Hu)

• timing of dementia onset relative to the onset of parkinsonism
• in patients who have dementia with Lewy bodies, dementia usually begins before the onset of parkinsonism, and at the latest it begins 1 year after the onset of parkinsonism

• voltage-gated potassium channel (VGKC) complex antibody
• prognosis is generally better for patients who have encephalopathy associated with antibodies targeting neural surface antigens than for patients who have encephalopathy associated with antibodies targeting intracellular antigens
• these target intracellular antigens:
•    antineuronal nuclear antibody-1 (ANNA-1, anti-Hu)
•    antineuronal nuclear antibody-2 (ANNA-2, anti-Ri)
•    glutamic acid decarboxylase 65 (GAD65) antibody
•    Purkinje cell cytoplasmic antibody type 2 (PCA-2)

• a test of executive function designed to assess inhibitory control
• read names of colors (eg, green, blue, red) that are printed in a different color than denoted by the word (eg, the word “green” printed in blue ink)
• they may impulsively say the color of the font when asked to read the word, or vice versa

construction of intersecting pentagons

tests language

tests memory

test attention and calculation ability

• a triad of rapidly progressive encephalopathy, branch retinal artery occlusions, and hearing loss
• headaches possible

depression

• performance on alternating pattern tasks
• require the subject to shift attention from one motor program to another in a purposeful way corresponding to specified goals

• a treatable cause of rapidly progressive dementia
• patient manifests with gastrointestinal symptoms (especially chronic diarrhea), systemic symptoms (fever, arthralgia) and neurologic involvement, which may include cognitive impairment as well as hemiparesis, seizures, or ataxia
• diagnosis can be made with CSF or blood polymerase chain reaction (PCR), or with intestinal biopsy, immunohistochemistry and PCR