Mild cognitive impairment

Abstract Mild Cognitive Impairment (MCI) is a disease between normal cognitive ageing and dementia. In recent years the term MCI has been recognized as a pre-dementia state, raising an important subject for investigation in the prevention of dementia. There are various terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer’s disease; most of them do not comprise all the areas related to MCI. A central cholinergic deficit is present in amnestic MCI with neuronal loss in the Meynert basal nucleus. It is estimated that the rate of progression to dementia is about 10% every year. The prevalence of MCI is 10%-11% and the risk of progression to dementia is about 5%-16%. The continual development of pharmacologic approaches to modify and delay the natural history of progression of the disease motivates a great interest in an earlier diagnosis

Mild Cognitive Impairment

Mild cognitive impairment (MCI) refers to cognitive decline from a previous level of functioning, both subjectively and by objective evidence. MCI is an intermediate stage of cognitive impairment between the normal cognitive aging and dementia. The concept of mild cognitive impairment originally evolved with an intention to characterize the pre-dementia phase of cognitive impairment. MCI is a known risk factor for dementia. Patients with MCI may represent an optimal target population for pharmacological and non-pharmacological interventions. The following chapter provides an overview of the concept of mild cognitive impairment, epidemiological data, current diagnostic criteria, clinical approach and management of MCI

Plasma biomarkers of neurodegeneration in mild cognitive impairment with Lewy bodies

BACKGROUND: Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another. METHODS: Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort. RESULTS: Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011). CONCLUSION: Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls

Prevalence of Pain on Admission by Level of Cognitive Impairment in Nursing Homes

Purpose: To provide contemporary estimates of pain by level of cognitive impairment among US nursing home residents without cancer. Methods: Newly admitted US nursing home residents without cancer assessed with the Minimum Data Set 3.0 at admission (2010-2016) were eligible (n=8,613,080). The Cognitive Function Scale was used to categorize level of cognitive impairment. Self-report or staff-assessed pain was used based on a 5-day look-back period. Estimates of adjusted prevalence ratios (aPR) were derived from modified Poisson models. Results: Documented prevalence of pain decreased with increased levels of cognitive impairment in those who self-reported pain (68.9% no/mild, 32.9% severe) and those with staff-assessed pain (50.6% no/mild, 37.2% severe staff-assessed pain). Relative to residents with no/mild cognitive impairment, pharmacologic pain management was less prevalent in those with severe cognitive impairment (self-reported: 51.3% severe vs 76.9% in those with no/mild; staff assessed: 52.0% severe vs 67.7% no/mild). Conclusion: Pain was less frequently documented in those with severe cognitive impairment relative to those with no/mild impairments. Failure to identify pain may result in untreated or undertreated pain. Interventions to improve evaluation of pain in nursing home residents with cognitive impairment are needed

Mild Cognitive Impairment in Parkinson's Disease - What Is It?

PURPOSE OF REVIEW: Mild cognitive impairment is a common feature of Parkinson’s disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson’s disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson’s disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson’s disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson’s disease. RECENT FINDINGS: Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson’s disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson’s provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. SUMMARY: Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson’s disease

Taking clinical judgment out of the equation : a call for the standardization of MCI diagnostic criteria and construction of a model to predict conversion to dementia.

Although the diagnostic criteria for mild cognitive impairment have evolved considerably since their inception, they remain varied and able to be interpreted and implemented in different ways depending on the judgment of the clinician. Because of this issue, a wide range of incidence, prevalence, and conversion rates are found in the research literature. Using data collected from 400 patients with amnestic mild cognitive impairment, limitations inherent in current mild cognitive impairment diagnostic criteria were addressed. First, using Alzheimer’s Disease Neuroimaging Initiative diagnostic criteria, an equation was constructed to predict conversion from mild cognitive impairment to dementia by analyzing the predictive ability of variables representative of a number of categories (i.e., demographic, psychiatric, functional, biomarker, imaging, and cognitive). This model accounted for over 60% of variance in conversion and exhibited an area under the curve of 0.93. Then, separate models were constructed using different applications of the current diagnostic criteria for mild cognitive impairment. As expected, criteria utilizing a one standard deviation clinical cutoff on a measure of delayed verbal recall in combination with the allowance for some functional change (i.e., scores =5 on the Functional Activities Questionnaire) exhibited the greatest utility of any combination of diagnostic criteria. Taken together, these results indicate that statistical equations can be constructed to predict conversion from mild cognitive impairment to dementia and be tailored for widespread clinical use. Moreover, these results show that the standardization of current diagnostic criteria for mild cognitive impairment is clearly needed

Onset of Mild Cognitive Impairment in Parkinson Disease

Objective: Characterize the onset and timing of cognitive decline in Parkinson disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants progressed from PD to PDD and 25 remained cognitively normal. Methods: Bayesian-estimated disease-state models described the onset of an individual’s cognitive decline across 12 subtests with a change point. Results: Subtests measuring working memory, visuospatial processing ability, and crystalized memory changed significantly 3 to 5 years before their first nonzero Clinical Dementia Rating and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits were the hallmark feature of imminent conversion of cognitive status. Episodic memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD, all 12 subtests showed modest linear decline without evidence of a change point. Conclusions: Longitudinal disease-state models support a prodromal dementia stage (PD-MCI) marked by early declines in working memory and visuospatial processing beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD affect motor ability (bradykinesia), working memory, and processing speed (bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory retrieval deficits manifest before eventual development of overt dementia. Tests of episodic memory may not be sufficient to detect and quantify cognitive decline in PD

Cognitive Reserve and Mild Cognitive Impairment

Background and Objectives Little is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age, APOE, and indicators of cognitive reserve on the RR of reversion vs progression using multistate Markov modeling. Methods We estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age, APOE, and potential cognitive reserve indicators: education, academic performance (high school grades), and written language skills (idea density, grammatical complexity). Results Of the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group and APOE, higher levels of education more than doubled the RR ratio of reversion vs progression. Novel cognitive reserve indicators were significantly associated with a higher adjusted RR of reversion vs progression (higher vs lower levels for English grades: RR ratio = 1.83; idea density: RR ratio = 3.93; and grammatical complexity: RR ratio = 5.78). Discussion Knowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention

Short-term memory binding in mild cognitive impairment

We showed that short-term memory (STM) binding is sensitive to sporadic and familial Alzheimer's disease (AD) but is not affected by healthy ageing, chronic depression in the elderly or other forms of dementia. STM binding deficits were also observed in individuals with a genetic susceptibility for AD in the preclinical stages. Hence, we aim to investigate longitudinally individuals with Mild Cognitive Impairment (MCI) using STM binding tasks. Here we report on preliminary cross-sectional results. A comprehensive neuropsychological test battery and a visual STM task were given to 21 MCI patients and 20 controls. The STM task required participants to recognise changes across two consecutive arrays presenting either single features (colour or shape) or feature bindings. The MCI group performed significantly poorer than controls on standard tests of memory, attention and on the binding condition of the STM task, but not on single feature conditions. Performance on the binding task and on standard memory tests did not correlate. Eight MCI patients clearly performed outwith the range of normality in the binding task. However, they did not significantly differ from the other 13 MCI patients in disease severity or demographic and neuropsychological variables. Six patients with binding impairments showed a multiple domain profile whereas ten patients with a preserved binding function showed an amnesic profile [Chi-square = 5.45, p = 0.020]. These results suggest that (1) the binding task is assessing a function different from other memory tests and that (2) STM binding may be differentially impaired in MCI subgroups