Does mild cognitive impairment always lead to dementia? A review

doi:10.1016/j.jns.2016.07.055

Journal of the Neurological Sciences

Volume 369, 15 October 2016, Pages 57-62

https://doi.org/10.1016/j.jns.2016.07.055 Get rights and content

Highlights

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We review current research on mild cognitive impairment (MCI) and its varying clinical outcomes.
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We focus primarily on MCI patients who revert to normal cognition or remain diagnostically stable.
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Rates of reversion and stability are higher than those of progression to dementia.
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Studies on the characterization and predictors of reversion and stability are limited.
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Increased study of these MCI trajectories can have important research and clinical implications.

Abstract

Mild cognitive impairment (MCI) has often been studied in its association with dementia, yet higher rates of reversion to normal cognition than progression to dementia suggest that MCI does not necessarily lead to dementia. Compared to the numerous studies on MCI progression, relatively few have examined reversion. This paper highlights the current literature on characteristics and predictive factors of MCI reversion, along with an overview of studies on MCI patients who remain diagnostically stable (i.e., MCI stability). Of the available studies, predictors of reversion have been noted in areas of cognitive/global functioning, demographic/genetic/biomarker data, and personality/lifestyle factors. However, there is a need for increased study of MCI reversion, considering that patients in this group can fluctuate between different trajectories of MCI (e.g., normal cognition back to MCI or even progression to dementia) within a given follow-up time period. Further examination of reversion via a longitudinal, multifactorial approach would better inform clinicians regarding the likelihood of reversion amongst MCI patients and subsequently modify treatment methods accordingly. Furthermore, researchers would have greater power in detecting treatment effects in their clinical intervention studies of early dementia by improving selection criteria to exclude MCI participants who are more likely to revert and remain cognitively normal than progress to a dementia.

Introduction

Mild cognitive impairment (MCI) refers to a transitional state between “normal aging” and dementia [10], [29]. MCI has been receiving much attention in research for its associated risk for dementia, particularly Alzheimer's disease (AD) [4], [5], [6], [7], [9], [12], [14], [15], [16], [24], [30], [37], [40], [42], [44], [47]. A meta-analysis of 41 MCI studies, using Mayo Clinic criteria [32], [34], identified the annual progression rate to dementia from MCI as 10% in clinical settings (8% of the entire sample progressed to AD) and 5% in community settings (7% of the entire sample progressed to AD) [26], suggesting that the annual MCI progression rate is low (5–10%). More importantly, these data clearly suggest that a large proportion of MCI patients do not progress to dementia and may revert to normal cognition. Surprisingly, few studies have examined the characteristics of MCI patients who follow this trajectory, and the available studies constitute only a small fraction of those on progression to dementia from MCI. Further, no review to date has fully integrated the findings of predictors of MCI reversion. Thus, the main purpose of this article is to examine the characteristics and/or predictive factors of MCI reversion. Additionally, we review the few but intriguing studies that evaluate the characteristics and/or predictors of patients with MCI who remain diagnostically stable over time. Articles for this review were selected from databases of Medline, Web of Science, Scopus, Embase, PsycINFO, and PubMed, using keywords “dementia,” “Alzheimer's disease,” “mild cognitive impairment,” “pre-MCI,” “reversion,” “normal cognition,” “aging,” “course of illness,” and “recovery.”

Section snippets

MCI reversion incidence/prevalence rates

To date, several studies have estimated the incidence rate of MCI reversion. We will focus on findings of incidence/prevalence rates of MCI reversion from community-based, rather than clinic/referral-based, studies to minimize subject selection bias and a spuriously high MCI prevalence rate often inherent in the latter. It is also important to consider that incidence rate of MCI reversion can vary depending on the MCI criteria used in the study. For example, the MCI criteria from the Mayo

Predictors of MCI reversion to normal cognitive function

Despite the relatively high rates of MCI reversion, significantly fewer studies have characterized MCI patients who follow this trajectory compared to studies of MCI progression. The first comprehensive MCI reversion study [22], using data from the National Alzheimer's Coordinating Center and revised MCI criteria by Petersen and Morris [33], found higher Mini Mental State Exam (MMSE) scores, lower Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Assessment Questionnaire (FAQ)

MCI stability prevalence/incident rates

While MCI patients may progress to dementia or revert to normal cognition, a large proportion of MCI patients may remain clinically stable (i.e., evidencing neither progression nor reversion) for their entire observed clinical course. Population/community-based studies from Italy, the United States, France, Korea, and Australia, using the Mayo-revised [29] or IWG-expanded [46] MCI criteria for participant selection, have documented MCI stability incident rates to range from 37% to 67% over the

Predictors of MCI stability

MCI stability is the largest subgroup that makes up the MCI group, yet data are not available to examine specific group characteristics or predict stability. In studies with any focus on MCI stability, this group has been used as a reference in modeling MCI progression or reversion, or described/compared to those with MCI progression and MCI reversion. For example, one study found the MCI stable group had significantly higher baseline MMSE scores than the MCI progression group, but lower scores

MCI trajectories: beyond MCI stability and MCI reversion

Do patients who have reverted to normal cognition remain cognitively normal over a long-term period? Do patients with stable MCI remain diagnostically static, if followed long enough? Available data offer both “yes” and “no” answers to these questions. A 12-year epidemiological study that used MCI criteria established in the Cardiovascular Health Study-Cognition Study [24] found nearly 35% of the incident MCI cases remained stable and 10% reverted over time. However, 10% of these incident MCI

MCI trajectories: implications

A growing number of research groups have found high rates of MCI reversion and stability, each of which is frequently higher than that of MCI progression to dementia. These rates appear to remain high when followed over time, contradictory to the generally held notion that MCI is an intermediate stage between normal aging and inevitable dementia. Additionally, there is evidence for highly variable trajectories of MCI, like those noted by Lopez et al. [24]. Based on existing studies, progression

Conclusions

MCI is a concept with clinical and prognostic heterogeneity that has been shown by numerous studies to not necessarily lead to dementia. Instead, rates of MCI reversion and stability are larger than those for progression to dementia, suggesting that progression is less frequent than research has previously depicted. Therefore, MCI reversion and stability are trajectories in need of further understanding and characterization. Results of such examination could help clinicians and researchers

Acknowledgments

This project was supported by the Friends of the UT Southwestern Alzheimer’s Disease Center.

References (47)

M.S. Albert et al.
The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheim. Dement. J. Alzheim. Assoc.
(2011)
H.H. Feldman et al.
Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the index study
Lancet Neurol.
(2007)
S. Gao et al.
Mild cognitive impairment, incidence, progression, and reversion: findings from a community-based cohort of elderly African Americans
Am. J. Geriatr. Psychiatry
(2014)
S. Gauthier et al.
Mild cognitive impairment
Lancet
(2006)
J.W. Han et al.
Predictive validity and diagnostic stability of mild cognitive impairment subtypes
Alzheim. Dement. J. Alzheim. Assoc.
(2012)
A.J. Jak et al.
Quantification of five neuropsychological approaches to defining mild cognitive impairment
Am. J. Geriatr. Psychiatry
(2009)
T. Ngandu et al.
A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial
Lancet
(2015)
R. Tokuchi et al.
Clinical and demographic predictors of mild cognitive impairment for converting to Alzheimer's disease and reverting to normal cognition
J. Neurol. Sci.
(2014)
B. Vellas et al.
Designing drug trials for Alzheimer's disease: what we have learned from the release of the phase III antibody trials: a report from the EU/US/CTAD Task Force
Alzheim. Dement. J. Alzheim. Assoc.
(2013)
M.W. Weiner et al.
The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception
Alzheim. Dement. J. Alzheim. Assoc.
(2013)

American Psychiatric Association

Diagnostic and Statistical Manual of Mental Disorders

(2013)

S. Artero et al.

Risk profiles for mild cognitive impairment and progression to dementia are gender specific

J. Neurol. Neurosurg. Psychiatry

(2008)

M.W. Bondi et al.

Mild cognitive impairment: a concept and diagnostic entity in need of input from neuropsychology

J. Int. Neuropsychol. Soc.

(2014)

L. Buratti et al.

Markers for the risk of progression from mild cognitive impairment to Alzheimer's disease

J. Alzheimers Dis.

(2015)

V. Drago et al.

Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage

J. Alzheimers Dis.

(2011)

C. Eckerstrom et al.

A combination of neuropsychological, neuroimaging, and cerebrospinal fluid markers predicts conversion from mild cognitive impairment to dementia

J. Alzheimers Dis.

(2013)

D. Ferreira et al.

Improving CSF biomarkers' performance for predicting progression from mild cognitive impairment to Alzheimer's disease by considering different confounding factors: a meta-analysis

Front. Aging Neurosci.

(2014)

A. Fleisher et al.

Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment

Arch. Neurol.

(2005)

M. Ganguli et al.

Mild cognitive impairment, amnestic type: an epidemiologic study

Neurology

(2004)

M. Ganguli et al.

How well do MCI criteria predict progression to severe cognitive impairment and dementia?

Alzheimer Dis. Assoc. Disord.

(2014)

J.J. Gomar et al.

Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative

Arch. Gen. Psychiatry

(2011)

J.J. Gomar et al.

Extension and refinement of the predictive value of different classes of markers in ADNI: four-year follow-up data

K. Hakansson et al.

Association between mid-life marital status and cognitive function in later life: population based cohort study

BMJ

(2009)

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Cognitive impairment as a risk factor for postoperative delirium in cardiac surgery based on the Mini Mental State Examination, in people over 60 years of age: A systematic review
2024, Psiquiatria Biologica
el delirium es un trastorno neurocognitivo cuya prevalencia aumenta con la edad. Su incidencia después de la cirugía cardiaca oscila entre 11 y 52%. Existe un gran número de estudios sobre los factores de riesgo que inciden en la aparición del delirium postoperatorio en la cirugía cardiaca, aunque la mayoría de ellos están orientados a factores fisiológicos, obviando a menudo la posible relevancia de los aspectos neuropsicológicos, como puede ser el deterioro cognitivo. El objetivo de este trabajo consistió en analizar la influencia del deterioro cognitivo como factor independiente de riesgo (predictor) en la aparición del delirium postoperatorio basado en el Mini Mental State Examination (MMSE), después de una cirugía cardiaca.
se llevó a cabo una búsqueda en las bases de datos PubMed, PsycInfo, Scopus y Web of Science. Se acotó la búsqueda a artículos publicados entre los años 2001 y 2022. Se obtuvieron 384 artículos. Se eliminaron aquellos repetidos y no relacionados con el tema, quedando un total de 8 artículos que cumplían con los criterios de selección. Esta revisión sistemática se llevó a cabo de acuerdo con los criterios de la declaración PRISMA 2020.
se observó una correlación estadísticamente significativa entre la medida del deterioro cognitivo, el MMSE y las distintas medidas de delirium postoperatorio, en la mayoría de estudios, por lo que se puede concluir que posiblemente un grado leve de deterioro cognitivo pueda ser condición suficiente para la probabilidad de aparición del delirium postoperatorio en cirugías cardiacas en pacientes mayores de 60 años. Por tanto, la evaluación del deterioro cognitivo mediante MMSE antes de una cirugía cardiaca podría ser útil para predecir el desarrollo de delirium postoperatorio en personas mayores de 60 años.
Delirium is a neurocognitive disorder whose prevalence increases with age. Its incidence after cardiac surgery ranges between 11% and 52%. There are a large number of studies on the risk factors that affect the appearance of postoperative delirium in cardiac surgery, although most of them are oriented to physiological factors, often ignoring the possible relevance of neuropsychological aspects, such as cognitive impairment. The objective of this work was to analyze the influence of cognitive impairment as an independent risk factor (predictor) in the appearance of postoperative delirium based on the Mini Mental State Examination (MMSE), after cardiac surgery.
A search was carried out in the databases PubMed, PsycInfo, Scopus and Web of Science. The search was limited to articles published between 2001 and 2022. 384 articles were obtained. Those that were repeated and not related to the topic were eliminated, leaving a total of 8 articles that met the selection criteria. This systematic review was carried out in accordance with the criteria of the PRISMA 2020 statement.
A statistically significant correlation was observed between the measure of cognitive impairment, the MMSE, and the different measures of postoperative delirium, in the majority of studies, so it can be concluded that possibly a mild degree of cognitive impairment may be a sufficient condition for the probability of appearance of postoperative delirium in cardiac surgeries in patients over 60 years of age. Therefore, assessment of cognitive impairment using MMSE before cardiac surgery could be useful to predict the development of postoperative delirium in people over 60 years of age.
Novel fluid biomarkers for mild cognitive impairment: A systematic review and meta-analysis
2023, Ageing Research Reviews
Mild cognitive impairment (MCI) is a well-established prodromal stage of dementia (e.g., Alzheimer’s disease) that is often accompanied by early signs of neurodegeneration. To facilitate a better characterization of the underlying pathophysiology, we assessed the available literature to evaluate potential fluid biomarkers in MCI. Peer-reviewed articles that measured cerebrospinal fluid (CSF) and/or peripheral biomarkers of neuronal injury (total-tau [T-tau], neurofilament light chain [NfL], heart-type fatty acid binding protein [HFABP], neuron-specific enolase, ubiquitin C-terminal hydrolase L1) and/or astroglial pathology (glial fibrillary acidic protein [GFAP], S100 calcium-binding protein B) in MCI and healthy controls were assessed. Group differences were summarized by standardized mean differences (SMDs) and 95% confidence intervals calculated using a random-effects model. Heterogeneity was quantified using I². A total of 107 studies were included in the meta-analysis and 10 studies were qualitatively reviewed. In CSF, concentrations of NfL (SMD = 0.69 [0.56, 0.83]), GFAP (SMD = 0.41 [0.07, 0.75]), and HFABP (SMD = 0.57 [0.26, 0.89]) were elevated in MCI. In blood, increased concentrations of T-tau (SMD = 0.19 [0.09, 0.29]), NfL (SMD = 0.41 [0.32, 0.49]), and GFAP (SMD = 0.39 [0.23, 0.55]) were found in MCI. Heterogeneity that was identified in all comparisons was explored using meta-regression and subgroup analysis. Elevated NfL and GFAP can be detected in both CSF and peripheral blood. Monitoring these biomarkers in clinical settings may provide important insight into underlying neurodegenerative processes in MCI.
FindMyApps compared with usual tablet use to promote social health of community-dwelling people with mild dementia and their informal caregivers: a randomised controlled trial
2023, eClinicalMedicine
FindMyApps is a tablet-based eHealth intervention designed to help people learn to use a tablet and find easy-to-use apps. This study evaluated the effectiveness of FindMyApps for supporting social health of people living with dementia, and sense of competence of their informal caregivers.
A single-centre, two-arm, non-blinded randomised controlled trial was conducted (Netherlands Trial Register NL8157). From 1st January 2020 to 31st July 2022, community-dwelling people in the Netherlands with a pre-established diagnosis of mild cognitive impairment (MCI) or dementia (Brief Cognitive Rating Scale 17–32), an informal caregiver and internet connection were allocated by block randomisation to receive FindMyApps or digital care-as-usual. Primary outcomes (measured at baseline and after three months) for people with dementia/MCI were self-management (Adult Social Care Outcomes Toolkit total score) and social participation (Maastricht Social Participation Profile frequency and diversity scores), and for caregivers, sense of competence (Short Sense of Competence Questionnaire total score). Between-group differences were tested by MANCOVA or ANCOVA (alpha = 0.05).
150 dyads were randomised (FindMyApps n = 76, care-as-usual n = 74). Follow-up data were available for 128 dyads (FindMyApps n = 64, care-as-usual n = 64), who were included in the analysis in the trial arm to which they were assigned. No harms of the intervention were identified. There were no statistically significant differences in outcomes for people with dementia/MCI at group level. Diagnosis and experiencing apathy appeared to be relevant effect modifiers of secondary outcomes (neuropsychiatric symptoms, positive affect, sense of belonging, and pleasurable activities). Caregivers who received FindMyApps had higher sense of competence at three months (F [1,123] = 7.01, p = 0.0092, η² = 0.054).
Overall we found no evidence that the FindMyApps intervention better supported social participation or self-management of people with MCI/dementia than digital care-as-usual. FindMyApps does seem to better support informal caregivers’ sense of competence. For people with a diagnosis of mild dementia and older people, better tailored interventions, implementation and outcome measures may be needed.
Marie Skłodowska Curie Actions Innovative Training Network H2020 MSCA ITN, grant agreement number 813196.
Comparing three neuropsychological subgrouping approaches in subjective and mild cognitive impairment from a naturalistic multicenter study
2023, Neurobiology of Aging
Subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are two clinical groups with an increased risk to develop dementia, but they are highly heterogeneous. This study compared three different approaches to subgroup SCI and MCI patients and investigated their capacity to disentangle cognitive and biomarker heterogeneity. We included 792 patients from the MemClin-cohort (142 SCI and 650 MCI). Biomarkers included cerebrospinal fluid measures of beta-amyloid-42 and phosphorylated tau, as well as visual ratings of medial temporal lobe atrophy and white matter hyperintensities on magnetic resonance imaging. We found that a more inclusive approach identified individuals with a positive beta-amyloid-42 biomarker; a less inclusive approach captured individuals with higher medial temporal lobe atrophy; and a data-driven approach captured individuals with high white matter hyperintensities burden. The three approaches also captured some neuropsychological differences. We conclude that choice of approach may differ depending on the purpose. This study helps to advance our current understanding of the clinical and biological heterogeneity within SCI and MCI, particularly in the unselected memory clinic setting.
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Decoding the diagnostic potential of T cell repertoires in peripheral blood of patients from amnestic mild cognitive impairment to Alzheimer's disease
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Review articleDoes mild cognitive impairment always lead to dementia? A review

Highlights

Abstract

Introduction

Section snippets

MCI reversion incidence/prevalence rates

Predictors of MCI reversion to normal cognitive function

MCI stability prevalence/incident rates

Predictors of MCI stability

MCI trajectories: beyond MCI stability and MCI reversion

MCI trajectories: implications

Conclusions

Acknowledgments

Alzheim. Dement. J. Alzheim. Assoc.

Lancet Neurol.

Am. J. Geriatr. Psychiatry

Lancet

Alzheim. Dement. J. Alzheim. Assoc.

Am. J. Geriatr. Psychiatry

Lancet

J. Neurol. Sci.

Alzheim. Dement. J. Alzheim. Assoc.

Alzheim. Dement. J. Alzheim. Assoc.

Diagnostic and Statistical Manual of Mental Disorders

Risk profiles for mild cognitive impairment and progression to dementia are gender specific

J. Neurol. Neurosurg. Psychiatry

Mild cognitive impairment: a concept and diagnostic entity in need of input from neuropsychology

J. Int. Neuropsychol. Soc.

Markers for the risk of progression from mild cognitive impairment to Alzheimer's disease

J. Alzheimers Dis.

Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage

J. Alzheimers Dis.

A combination of neuropsychological, neuroimaging, and cerebrospinal fluid markers predicts conversion from mild cognitive impairment to dementia

J. Alzheimers Dis.

Improving CSF biomarkers' performance for predicting progression from mild cognitive impairment to Alzheimer's disease by considering different confounding factors: a meta-analysis

Front. Aging Neurosci.

Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment

Arch. Neurol.

Mild cognitive impairment, amnestic type: an epidemiologic study

Neurology

How well do MCI criteria predict progression to severe cognitive impairment and dementia?

Alzheimer Dis. Assoc. Disord.

Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative

Arch. Gen. Psychiatry

Extension and refinement of the predictive value of different classes of markers in ADNI: four-year follow-up data

Association between mid-life marital status and cognitive function in later life: population based cohort study

BMJ

Review article
Does mild cognitive impairment always lead to dementia? A review