Rapidly Progressive Alzheimer Disease

Abstract

Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

Progression of Alzheimer’s Disease: A Longitudinal Study in Norwegian Memory Clinics

“…Patients with an average annual decrease in the MMSE score of < 1 point, 1-6 points or ≥ 6 points were classified as slow [6,8,9], intermediate [9], and rapid progressors, respectively [9,10].…”

“…Using the Mini-Mental State Examination (MMSE) to measure cognition, the average loss is between 1.5 and 2.3 points per year [5,6,8,9]. A rapid cognitive decline, defined as a decrease of 3 to 5 points per year on the MMSE [8], has been shown in 10-30% of AD cases, depending on the threshold set and the population studied [8,10].…”

Plasma prion protein concentration and progression of Alzheimer disease

“…The APOE status and its relation to AD progression is still matter of debate as findings are contradictory. 33 Our study has limitations and strengths. Regarding the former, the medium term observation period has to be mentioned.…”

Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases

“…63 Recently, the Prion Surveillance Centers in the US and Europe independently described a novel subgroup of patients who have rapidly progressive dementia that clinically imitates prion diseases, and which, after exhausting neuropathological investigation and prion protein gene sequencing, is concluded to be rapidly progressive late-onset AD (rpAD). 64,[71][72][73][74] The data collected from multiple Prion Centers uniformly demonstrate the absence of positive family history or comorbidity, the presence of distinctive clinical characteristics, and a frequency of e4 alleles in the APOE gene that corresponds to the general population. A systematic investigation of the genetics and molecular pathology of Aβ and tau in those patients should lead to the identification of biological factors responsible for the variable progression rates of AD.…”

“…Additional polymorphisms in several recently identified genes may moderately increase the risk of disease. 63 Thus, the extensive phenotypic variability of AD with variable progression rates, 64,65 clinical symptomatology, 66 and pathological findings 67,68 suggests a complex impact of different structural forms of misfolded Aβ and tau proteins, 69 variable genetic backgrounds, 63 and compensatory mechanisms ("cognitive reserves"). 70 While the genetic and environmental factors linked to the risk of developing AD are well recognized, the factors leading to variable progression rates of late-onset AD are unknown.…”