When Dementia Progresses Quickly: A Practical Approach to the Diagnosis and Management of Rapidly Progressive Dementia

Abstract

Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

CJD mimics and chameleons

“…There are some excellent and comprehensive reviews, [1][2][3] including by Murray,4 in this journal. The archetypal diagnosis is Creutzfeldt-Jakob disease (CJD), and most experiences have been reported from specialist prion disease referral centres and from a small number of specialist cognitive clinics.…”

Clinicopathological case: rapid cognitive decline in an older man

“…Rapidly progressive dementias are defined as dementias that evolve over days to weeks or subacutely over months 7. Analysis from the five largest case series of rapidly progressive dementias identified 675 patients, with a cause established in 95% of cases.…”

“…Alzheimer's dementia is unlikely to be this rapid unless his decline had been begun earlier than his family realised, nor would it fit with motor neurone disease or corticobasal degeneration syndrome, but prion disease is possible (and of course we are at the home of prion disease). Creutzfeldt-Jakob disease can be extremely quick and deterioration to death within 25 days has been reported but a more typical duration would be 6–18 months 7. Antemortem diagnosis of prion disease can be difficult and is based on MRI (classically showing cortical ribboning, basal ganglia and thalamus hyperintensity on diffusion-weighted imaging and fluid-attenuated inversion recovery), electroencephalogram (generalised slowing and periodic polyspike-wave complexes and sharp waves that may not become apparent until late in the disease) and CSF analysis (normal or minimally raised white cell count, total tau protein concentration elevated to >1200 pg/mL, protein 14.3.3 positive on Western blot.…”

“…Patients with dementia with Lewy bodies may be particularly at risk of prolonged or permanent cognitive decline following surgery or exposure to antipsychotic medication 7. Severe neuroleptic sensitivity is characterised by sudden onset sedation, increased confusion, immobility and muscle rigidity, and 30%–50% of patients with dementia with Lewy bodies experience severe reactions even at low doses, which can be fatal within days to weeks 13 15…”

Subacute progressive aphasia: a rare presentation of Creutzfeldt–Jakob disease

“…Therefore, a prompt evaluation is critical, especially looking for some treatable conditions. Among RPDs, CJD represents the most common cause (annual incidence of 1 per 1,000,000 population) [1]. Most cases of CJD exhibit a characteristic clinical course consisting of rapid cognitive decline, myoclonus, usually associated with encephalogram abnormalities and CSF elevation of 14.3.3 protein, and a rapid fatal course [2].…”