Rapidly Progressive Dementia

Rapidly progressive dementia refers to cognitive and/or behavioral deficits that evolve over weeks to months, much more rapidly than with traditional neurodegenerative diseases such as Alzheimer dementia. Treatable conditions are found in up to 20% of those with rapidly progressive dementia, which is far more often than in patients with more chronically evolving dementia.

A.

Obtain a careful history to distinguish between a true rapid decline and a subacute worsening of a preexisting more chronic progressive neurodegenerative disorder. This may require careful focused questioning about the patient’s ability to perform specific cognitive tasks (dealing with finances, navigation) over the past few years. Assess medication use with attention to any potential temporal relationship between new medications or changes and the onset of symptoms. Certain toxic exposures (lead, mercury, bismuth) can cause relatively rapid cognitive and behavioral changes. Consider thiamine, niacin, and B12 deficiency. Screen for metabolic derangements, thyroid disease, and syphilis or HIV infection.
B.

Limbic encephalitis in the patient with cognitive decline over weeks suggests autoimmune encephalitis (see Chapter 115 ). Infectious causes tend to progress more rapidly (i.e., over days), though in atypical cases may have a more insidious course.
C.

Creutzfeldt-Jakob disease (CJD) is a prion disease causing spongiform encephalopathy. Startle myoclonus and ataxia are frequent clinical findings, as are periodic sharp wave complexes on electroencephalogram (EEG). Early in the disease, brain magnetic resonance imaging (MRI) may be normal; later, characteristic MRI signs appear. Routine cerebrospinal fluid (CSF) studies are often normal. Elevated CSF levels of the 14-3-3 protein support the diagnosis and the real-time quaking-induced conversion (RT-QuIC) assay is confirmatory. Brain biopsy may be necessary in uncertain cases. There is no specific treatment for CJD.
D.

Central nervous system (CNS) vasculitis may present with rapidly accumulating infarctions over weeks to months. Headache is a frequent feature, and CSF pleocytosis may be present. As the affected vessels are often small-medium in caliber, noninvasive vessel imaging (magnetic resonance angiogram [MRA]/computed tomography angiogram [CTA]) is often normal, and catheter angiography should be pursued recognizing that even this may be negative if the vasculitis involves only the very small vessels. Brain biopsy is necessary for diagnostic confirmation. Treatment is usually steroids and cyclophosphamide. Intravascular lymphoma may mimic CNS vasculitis clinically and radiographically.
E.

It is essential that MRI be performed with susceptibility weighted images (i.e., GRE, SWI) to identify microhemorrhages, which are the cardinal feature of amyloid angiopathy (AA). Patients with AA may have rapid cognitive decline due to accumulation of large numbers of microhemorrhages. Rarely, an inflammatory component may be present (angiitis), resulting in vasogenic edema and in some cases even giving the appearance of a mass lesion. While there is no specific treatment for AA itself, amyloid angiitis is usually highly responsive to steroids.
F.

While extremely rare, dural arteriovenous fistulas (dAVFs) can cause rapid cognitive decline. MRI will show parenchymal lesions consistent with venous edema; abnormal flow voids consistent with dilated vessels on T2 images may suggest the diagnosis. Note that dAVFs are often occult on MRA or CTA, such that if the diagnosis is suspected, catheter angiography is required.
G.

Thiamine deficiency must be considered in any patient with rapid development of encephalopathy over days to weeks; the presence of eye movement abnormalities (nystagmus or ophthalmoparesis) and ataxia should increase suspicion (Wernicke-Korsakoff syndrome), but neither of these findings are universally present. Chronic alcoholics are particularly susceptible. Clinical suspicion or characteristic MRI findings suggesting Wernicke-Korsakoff syndrome should trigger immediate thiamine administration. A whole blood thiamine level may be sent to confirm the diagnosis, but should not delay treatment.
H.

Brain MRI may be normal or show only nonspecific abnormalities in several important causes of rapidly progressive dementia. Hashimoto encephalopathy is a rare condition associated with antithyroid antibodies that may cause rapidly progressive dementia. Concomitant thyroid disease is often but not always present. The condition is extremely steroid responsive. Suspicion for paraneoplastic/autoimmune encephalitis should be raised when the patient has a known malignancy, but certain types often occur without underlying cancer. Accompanying neurologic signs may provide important clues as to which antibody may be mediating the clinical syndrome (see Chapter 115 ). CJD may occur with a normal brain MRI and routine CSF studies (see section C).
I.

Extremely rare causes of rapidly progressive dementia may be suggested by particular accompanying symptoms or signs as outlined in the chart; MRI is usually abnormal in some but not all of these conditions. Prolonged EEG monitoring should be considered to capture the rare patient in nonconvulsive status epilepticus.
J.

A variety of other specific causes may be identified on brain MRI, including subdural hematoma, tumors, infection (i.e., focal mass lesions, progressive multifocal leukoencephalopathy), demyelinating disease, inflammatory diseases, and hydrocephalus.