Assessing the progression of mild cognitive impairment to Alzheimer's disease: current trends and future directions

Abstract

With the advent of advances in biomarker detection and neuropsychological measurement, prospects have improved for identifying and tracking the progression of Alzheimer's disease (AD) from its earliest stages through dementia. While new diagnostic techniques have exciting implications for initiating treatment earlier in the disease process, much work remains to be done to optimize the contributions of the expanding range of tools at the disposal of researchers and clinicians. The present paper examines recent work in cerebrospinal fluid biomarkers, magnetic resonance imaging, positron emission tomography, neuropsychological measures, and functional assessment. The strengths and weaknesses of current methodologies are explored and discussed. It is concluded that AD from its mild cognitive impairment state through dementia represents a continuous process, and that progression over time can best be accomplished by interval-level variables. Biomarkers that are most sensitive to early AD may not be the most optimal for monitoring longitudinal change, and it is likely that multivariate models incorporating cognitive measures, functional variables and biomarker data will be the most fruitful avenues for future research.

A New Scale for the Evaluation of Proactive and Retroactive Interference in Mild Cognitive Impairment and Early Alzheimer’s Disease

“…Traditional neuropsychological measures, initially developed for the assessment of dementia, are often not well suited to identify the subtle changes in cognition, that manifest during the earliest stages of disease. As such, more sensitive neuropsychological assessment measures are required to identify the earliest neurocognitive deficits associated with AD, and other neurodegenerative disorders [1].…”

Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes

“…None of these clinical trials has achieved their expected therapeutic end points and therefore there are no approved treatments for MCI [2]. These results have caused some concerns about the insufficient sensitivity of the ADAS‐cog scale in mapping and tracking the early stages of the disease [4].…”

An assessment by the Statin Cognitive Safety Task Force: 2014 update

“…7 On follow-up, conversion rates to normal cognition were formerly thought to be in the range of 25% to 30%, although recent studies suggest lower conversion rates for those with impairments in multiple cognitive domains or those with amnestic MCI. [22][23][24][25] Additional recent data suggest that conversion of MCI to normal cognition may be almost nonexistent, and conversion to normal cognition does not preclude progression in the future. 26 Determining a relationship between statins and cognitive impairment is further complicated by the ''worried well'' (ie, patients who have subjective cognitive complaints in the absence of subtle or overt cognitive impairment).…”