Rapidly Progressive Dementia

Background

• Rapidly progressive dementia (RPD) is a syndrome caused by numerous conditions, many of which are uncommon.
  • There is no generally accepted definition of RPD but it is usually considered to be a dementia where the time from first symptoms to dementia is less than 2 years.
  • Dementia can be defined as the gradual development of cognitive impairment sufficient to impair daily function
  • The typical mode of onset is more acute or subacute (weeks to months) in contrast to most neurodegenerative disorders where the exact date of onset is often difficult to identify.
• Consider more common causes, such as rapid forms of neurodegenerative diseases and sporadic Creutzfeldt-Jakob (sCJD), as well as potentially reversible causes of RPD (that is, vascular, infectious, autoimmune, metabolic causes) early in the disease course.
• The incidence of rapidly progressive dementia varies in different clinical settings due to varied referral patterns, definitions of RPD, and multiple different causes.
  • Depending on the definition, 10%-30% of sporadic symptomatic Alzheimer disease (AD) are rapidly progressive.
  • Case series from prion disease reference centers report that sCJD is the most common cause for RPD followed by AD, but these have significant referral bias.

Evaluation

• In the absence of specific clues from the history and physical that point to a specific cause, a systematic evaluation strategy should be used to avoid missing a treatable cause of RPD.
• Detailed history from a reliable collateral source should include baseline function, educational history, timeline of symptoms, and details of neurological and systemic symptoms.
• A systematic approach to diagnosis is important to organized diagnostic evaluation.
• Consider using mnemonic approach such as VITAMIN-C to consider all possible causes:
  • V = vascular
  • I = infectious
  • T = toxic-metabolic
  • A = autoimmune
  • M = malignancy
  • I = iatrogenic
  • N = neurodegenerative
  • S = systemic
  • C = congenital and genetic
• The list of potential causes of RPD is extensive; see differential diagnosis for specific potential causes.
• Consider potentially treatable causes of RPD early in evaluation. Look for conditions such as:
  • toxic/metabolic causes
  • viral encephalitides
  • autoimmune encephalitis
  • vitamin deficiencies such as B12 or B1 deficiency
  • drugs or toxins
  • Whipple disease
• Note that in in elderly or frail patients, simple metabolic disturbance or infection may be enough to present as a RPD, particularly in patients with underlying mild dementia.
• Obtain magnetic resonance imaging (MRI), electroencephalography (EEG), and cerebrospinal fluid evaluation in most cases of RPD.
• Early investigations suggested include blood, urine, cerebrospinal fluid (CSF), imaging, and other tests focused on identifying common and reversible conditions.
• Investigations can be grouped into earlier (tier 1) and later (tier 2) evaluation depending on outcome of earlier investigations.

Management

• The treatment of rapidly progressive dementia is dictated by the presumed cause of impairment.
• Consider treatment with empiric strategies when an immune or inflammatory-mediated cause is presumed and infectious causes have been reasonably excluded.
• Consider early trial of treatment for autoimmune encephalitis unless infection or lymphoma likely.
• While treatment is limited, consider symptomatic treatment options for RPD due to degenerative disorders:
  • for AD consider acetylcholinesterase inhibitors or memantine
  • for dementia with Lewy bodies consider cholinesterase inhibitor and depression treatment with selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)
  • for behavioral-variant frontotemporal dementia consider SSRI or SNRI for behavioral syndrome
  • for sporadic Creutzfeldt-Jakob disease (sCJD), consider symptomatic management of depression and anxiety with SSRI, myoclonus with clonazepam or levetiracetam, cognition with acetylcholinesterase inhibitor.