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Objective:: Cognitive impairment is a hallmark of mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD). Although the cognitive profile of these patients and its association with activities of daily living (ADLs) is well documented, few studies have assessed deficits in fine motor dexterity and their association with ADL performance. The objective of this research paper is to evaluate fine motor dexterity performance among MCI and AD patients and to investigate its association with different aspects of ADLs. Methods:: We assessed normal aging controls, patients with multiple- and single-domain amnestic MCI (aMCI), and patients with mild AD. Fine motor dexterity was measured with the Nine-Hole Peg Test and cognitive functioning by the Mattis Dementia Rating Scale. We analyzed the data using general linear models. Results:: Patients with AD or multiple-domain aMCI had slower motor responses when compared to controls. AD patients were slower than those with single-domain aMCI. We found associations between cognition and instrumental ADLs, and between fine motor dexterity and self-care ADLs. Conclusion:: We observed progressive slowing of fine motor dexterity along the normal aging-MCI-AD spectrum, which was associated with autonomy in self-care ADLs.
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Impairment of fine motor dexterity in mild cognitive
impairment and Alzheimer’s disease dementia:
association with activities of daily living
Jonas J. de Paula,
Maicon R. Albuquerque,
Guilherme M. Lage,
Maria A. Bicalho,
Marco A. Romano-Silva,
Leandro F. Malloy-Diniz
Instituto Nacional de Cie
ˆncias e Tecnologia em Medicina Molecular (INCT-MM), Faculdade de Medicina, Universidade Federal de Minas
Gerais (UFMG), Belo Horizonte, MG, Brazil.
Departamento de Psicologia, Faculdade de Cie
ˆncias Me
´dicas de Minas Gerais (FCMMG), Belo
Horizonte, MG, Brazil.
Departamento de Educac¸a
´sica, Universidade Federal de Vic¸osa (UFV), Vic¸osa, MG, Brazil.
Departamento de
´sica, UFMG, Belo Horizonte, MG, Brazil.
Departamento de Clı
´nica Me
´dica, Faculdade de Medicina, UFMG, Belo Horizonte, MG,
Departamento de Sau
´de Mental, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil.
Objective: Cognitive impairment is a hallmark of mild cognitive impairment (MCI) and Alzheimer’s
disease dementia (AD). Although the cognitive profile of these patients and its association with
activities of daily living (ADLs) is well documented, few studies have assessed deficits in fine motor
dexterity and their association with ADL performance. The objective of this research paper is to
evaluate fine motor dexterity performance among MCI and AD patients and to investigate its
association with different aspects of ADLs.
Methods: We assessed normal aging controls, patients with multiple- and single-domain amnestic
MCI (aMCI), and patients with mild AD. Fine motor dexterity was measured with the Nine-Hole Peg
Test and cognitive functioning by the Mattis Dementia Rating Scale. We analyzed the data using
general linear models.
Results: Patients with AD or multiple-domain aMCI had slower motor responses when compared to
controls. AD patients were slower than those with single-domain aMCI. We found associations
between cognition and instrumental ADLs, and between fine motor dexterity and self-care ADLs.
Conclusion: We observed progressive slowing of fine motor dexterity along the normal aging-MCI-AD
spectrum, which was associated with autonomy in self-care ADLs.
Keywords: Dementia; mild cognitive impairment; Alzheimer’s disease; motor coordination; activities
of daily living; nine-hole peg test; motor dexterity
Patients with Alzheimer’s disease dementia (AD) exhibit a
progressive impairment of episodic memory and other
cognitive functions, which affects functional status.
In the
early symptomatic stages, known as mild cognitive impair-
ment (MCI), cognitive symptoms occur with only slight loss of
Cross-sectional and longitudinal studies suggest
that cognitive decline (the main difference between normal
aging and MCI) precedes functional decline (the main
difference between MCI and AD).
This pattern is
associated with the main biomarkers of AD and moderated
by several factors, including cognitive reserve.
Motor impairment may emerge as a phenotype of cognitive
Deficits in fine motor dexterity are associated with
functional loss, and are especially impairing of the basic and
instrumental aspects of activities of daily living (ADLs).
Studies have shown deficits in fine motor skills in patients
with AD and MCI.
However, this evidence comes from
complex or experimental motor tasks, involving sophisticated
apparatuses usually available only in research settings. This
type of test is called process-oriented because mechanisms
involved in motor control are of primary interest. Clinical
assessment of motor impairments with single, user-friendly,
and easily interpretable tests, known as task-oriented tests, is
more feasible.
Taking into account previous reports of motor impairment
and ADL loss in MCI and AD, we hypothesized that motor
complications would be detectable in simple, clinically
oriented motor tasks, and that motor and cognitive perfor-
mance might be differently associated with ADLs. The
objective of this study was to evaluate group differences
among normal controls, patients with MCI, and patients with
AD in a simple motor task, and to investigate potential
associations with functional performance.
We evaluated a sample of 20 healthy controls, 34 patients
diagnosed with single-domain amnestic MCI (aMCI),
32 with multiple-domain amnestic MCI (MDaMCI), and
38 with mild AD. Healthy controls had no subjective
Correspondence: Jonas Jardim de Paula, Universidade Federal de
Minas Gerais, Faculdade de Medicina, Instituto Nacional de Cie
e Tecnologia e em Medicina Molecular, Av. Alfredo Balena, 190,
CEP 30130-100, Belo Horizonte, MG, Brazil.
Submitted Dec 02 2015, accepted Jan 23 2016.
Revista Brasileira de Psiquiatria. 2016;38:235–238
˜o Brasileira de Psiquiatria
cognitive complaint, no history of mental or neurological
diseases, and no evidence of cognitive impairment on
objective tests or functional impairment according to a
clinical interview. Patients were evaluated during 2010 to
2013 at an outpatient clinic, within a major university
hospital, that provides specialized investigation and care
of memory deficits in the elderly population.
The diagnosis of amnestic MCI was established on the
basis of: subjective cognitive complaints confirmed by an
informant; objective impairment in neuropsychological tests
of memory (aMCI), language, visuospatial abilities, or
executive functions (MDaMCI); preserved global cognitive
functioning; and absence of functional impairment or mild
impairment restricted to complex aspects of ADLs, accord-
ing to a clinical interview, as described in previous
Diagnosis of AD followed standard clinical
Patients who exhibited active psychotic symp-
toms were excluded from the final sample. All participants
underwent a neuropsychological assessment as published
elsewhere, with tests included in the diagnosis process
and a complementary protocol not involved in the establish-
ment of cognitive status.
Diagnoses were established
by consensus of an expert board, based on clinical,
cognitive, and functional data. All participants and their
caregivers (in cases of dementia) gave written consent for
This study is part of a broader research project
investigating clinical and neurobiological markers of
depression and dementia and their associations. This
project was approved by the local Research Ethics
Committee and is in accordance with the Declaration of
Helsinki. The present study is part of the first author’s
doctoral dissertation, the results of which have been
published elsewhere.
Functional status was reported by each participant’s
caregivers during an interview conducted as part of the
neuropsychological assessment, using the General Activ-
ities of Daily Living Scale (GADL).
This measure involves
sub-scores of basic ADLs (self-care) and instrumental
ADLs (domestic and complex). Higher scores are repre-
sentative of higher independence in daily life. We devel-
oped a scale using the most common ADLs performed by
older adults with low formal education and conducted a
validation study for this specific population, following the
recommendations discussed by Sikkes et al.
As a global
measure of cognitive functioning, we used the total score of
the Brazilian version of the Dementia Rating Scale (DRS)
and a brief neuropsychological battery designed for the
assessment of attention, executive functions, language,
visuoconstructional skills, and memory. Higher scores in
this test represent better cognitive performance. We
created a fine motor dexterity measure summing the time
of four trials (two with the dominant and two with the non-
dominant hand) of the Nine-Hole Peg Test.
In this task-
oriented test, the subject must put nine pegs in nine holes
organized on a small board and subsequently remove
them, as fast as possible. The test is widely used in the
assessment of neurological disorders
and a commercial
version is available.
We analyzed our data by general linear models. To
assess group differences in fine motor dexterity, we
entered the Nine-Hole Peg test as the dependent
measure, the group as a fixed factor, and age and
education as covariates. We compared the estimated
marginal means by corrected (Sidak) post-hoc tests. The
association between fine motor dexterity and ADLs was
tested using a multivariate general linear model with the
three GADL measures as dependent measures, group as
a fixed factor, and age, education, Nine-Hole Peg Test,
and DRS total score as covariates. Statistical significance
was established at p p0.05. The partial eta-squared
represents the effect sizes for previous analysis.
The results suggest a progressive pattern of impairment
in motor task performance. The general linear model used
to assess group differences in fine motor dexterity was
significant and showed a large effect size (F = 14.60, p o
0.001, Z
= 0.38). We found a significant main effect for
diagnosis (F = 10.36, p o0.001, Z
= 0.21) and formal
education (F = 11.02, p = 0.001, Z
= 0.09), but not for
age (F = 2.27, p = 0.135, Z
= 0.02). The model for DRS
total score was also significant (F = 103.29, p o0.001,
= 0.81). Again, we found a significant main effect for
diagnosis (F = 132.38, p o0.001, Z
= 0.77) and formal
education (F = 12.84, p o0.001, Z
= 0.10), but not for
age (F = 0.74, p = 0.391, Z
Figure 1A shows the estimated marginal means for fine
motor dexterity and cognitive functioning in each group. We
found no significant differences on comparison of controls
vs. aMCI (p = 0.568), aMCI vs. MDaMCI (p = 0.195), or
MDaMCI vs. AD (p = 0.719). Significant differences were
found on comparison of controls vs. MDaMCI (p = 0.009),
controls vs. AD (p o0.001), and aMCI vs. AD (p = 0.004).
In DRS scores, group differences were significant for all
comparisons (p o0.001).
Figure 1B synthesize the contributions of fine motor
dexterity and cognitive functioning to each aspect of ADLs.
The multivariate general linear models for ADL measures
were all significant. In the complex ADL model (F = 23.72,
po0.001, Z
= 0.44), cognitive functioning was the main
predictor (F = 56.39, p o0.001, Z
= 0.32), while fine motor
dexterity was not significant (F = 0.85, p = 0.772, Z
The domestic ADL model (F = 12.26, p o0.001, Z
= 0.29)
followed the same pattern, but showed lower effect sizes for
cognitive functioning (F = 0.26, p o0.001, Z
= 0.18) and still
no significance for fine motor dexterity (F = 0.14, p = 0.839,
o0.01). However, the model for self-care ADLs was
significant (F = 11.28, p o0.001, Z
= 0.27) and showed the
opposite pattern, with a significant main effect for fine motor
dexterity (F = 17.88, p o0.001, Z
= 0.13) but not for
cognitive functioning (F = 2.91, p = 0.091, Z
= 0.02). Age
and education were not significantly associated with ADL
performance in this sample (all p 40.05).
Our results suggest that the intensity/severity of cognitive
deficits is associated with greater slowness on a fine
motor dexterity measure. We also documented differential
236 JJ de Paula et al.
Rev Bras Psiquiatr. 2016;38(3)
236 JJ de Paula et al.
patterns of association of motor and cognitive functioning
with basic and instrumental ADLs.
Motor evaluation is often neglected in cases of AD, due to
the more overt cognitive features included in the diagnosis.
Recent data, however, suggest that motor impairment may
be a consequence of cognitive impairment.
Multiple brain
regions and their connectivity are essential to maintenance
of good performance (speed and accuracy) in timed tasks.
The progressive brain atrophy and dysfunction of AD
impair connectivity and lead to a widespread range of
cognitive deficits.
In turn, this progressive reduction of
brain connectivity and consequent inefficient interactions
between specific cognitive functions characterize the MCI
and dementia stages of AD as a disconnection syndrome.
This may underlie the slowness in motor tasks found in
our study. This reduction may also be a compensatory
mechanism to maintain test accuracy (not measured in the
current study), increasing the connectivity of multiple brain
regions. Using a finger-tapping test, Scheller et al.
an increased pattern of connectivity in cortical motor regions
in patients at high risk of motor impairment (preclinical
patients with the genetic mutation associated with Hunting-
ton’s disease).
As seen in our results and in previous studies,
changes in fine motor dexterity and hand function are
associated with functional impairments in self-care activities.
A longitudinal decline in instrumental ADLs usually precedes
the decline of basic/self-care ADLs.
Although predictors
Figure 1 A) Estimated marginal means for fine motor dexterity (summed time of four trials in 9HPT) and cognitive functioning
(DRS total score) after covariating for age (mean, 74.2) and education (mean, 4.6). Significant group differences in fine motor
dexterity were found between controls and MDaMC (p = 0.009), controls and AD (p o0.001), and aMCI and AD (p = 0.004).
For cognitive measures, all comparisons were significant (p o0.001), following the pattern controls 4aMCI 4MDaMCI 4AD.
B) Effect sizes (partial eta-squared) from the main effects of fine motor dexterity and cognitive functioning in self-care,
instrumental-domestic, and instrumental-complex ADLs (AD). We found specific contributions of cognitive functioning
to instrumental ADLs and fine motor dexterity for self-care ADLs. 9HPT = Nine-Hole Peg Test; AD = Alzheimer’s disease
dementia; ADLs = activities of daily living; aMCI = single-domain amnestic mild cognitive impairment; DRS = Dementia Rating
Scale; MDaMC = multiple-domain amnestic mild cognitive impairment.
Rev Bras Psiquiatr. 2016;38(3)
Fine motor dexterity in aMCI-AD and ADL 237
of instrumental ADL changes have been documented,
there are relatively few established predictors of basic ADL
decline in MCI-AD. Our results may have important
implications for patient follow-up and for the prediction of
more severe functional deficits in MCI and dementia.
These results might affect routine clinical assessment
practices, e.g., to incorporate specific measures of fine
motor dexterity in the evaluation of patients with MCI and
AD. Using both cognitive and motor assessments would
allow the clinician to compute better estimates of functional
performance, as seen in other neurocognitive disorders,
such as Parkinson’s disease dementia.
The impairment of
fine motor coordination observed in MDaMCI is important
from the perspective of MCI-AD conversion.
Our study has limitations that should be addressed.
First, its cross-sectional design limits its potential to set
predictive models of functional loss. In a longitudinal
perspective, we could test whether patients with motor
deficits are more likely to experience long-term functional
loss. A second limitation is the absence of patients with
moderate/severe dementia, in whom impairment in basic
ADLs would be more obvious and add variability to our
data. We also excluded patients with active psychotic
symptoms. This may restrict the representativeness of
our findings, as such symptoms are relatively common in
patients with dementia or MCI.
We believe that our results, using a simple and widely
available task-oriented test, are sensitive to detect motor
deficits in these populations. However, these results should
be replicated in a longitudinal design. Participants with
impaired motor dexterity may be at higher risk of loss
of essential ADL performance, and non-pharmacological
interventions focusing on fine motor dexterity may improve
performance in these ADLs. If these findings are corrobo-
rated, this might allow clinicians to predict and intervene
earlier in patients at higher risk of functional decline.
This study was supported by Fundac¸a
˜o de Amparo e
Pesquisa do Estado de Minas Gerais (FAPEMIG; grant
INCT-MM FAPEMIG CBB-APQ-00075-09, APQ-01972/
12-10, APQ-02755-10) and by Conselho Nacional de
Desenvolvimento Cientı
´fico e Tecnolo
´gico (CNPq; grant
The authors report no conflicts of interest.
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... When more papers involved the same population, the first paper in order of publication was included. Eighteen articles were selected (see Table 1, Ref. [29,[32][33][34][35][36][37][43][44][45][95][96][97][98][99][100][101][102]). Different methodological approaches have been used for assessing hand movements in MCI, e.g., reaching tasks [37,95,96], visuomotor integration tasks [45,97], the finger-tapping task [32,34,43,44,98,99], handwrit-ing/graphomotor tasks [33,35,36,100], and the Pegboard test [29,32,44,101,102]. ...
... Eighteen articles were selected (see Table 1, Ref. [29,[32][33][34][35][36][37][43][44][45][95][96][97][98][99][100][101][102]). Different methodological approaches have been used for assessing hand movements in MCI, e.g., reaching tasks [37,95,96], visuomotor integration tasks [45,97], the finger-tapping task [32,34,43,44,98,99], handwrit-ing/graphomotor tasks [33,35,36,100], and the Pegboard test [29,32,44,101,102]. The following is a brief overview of the studies included in this review. ...
... They also demonstrated that PwnaMCI-md were more compromised than PwaMCI-md; however, both groups showed greater difficulties than PwaMCI. In line with these findings, De Paula et al. [102] reported that PwAD showed reduced fine motor dexterity than PwaMCI, whereas PwaMCI-md showed a similar degree of fine motor deterioration compared to PwAD. In sum, except for a few studies finding no hand movement deficits in MCI [32,35,43,95,101,102], the majority of experimental evidence suggests that hand movements in PwMCI are slower [35,37,45,96,97,100], less coordinated [29,[32][33][34]43,98,99,101,102], and less accurate [35,36,45] as compared with HCs. ...
Full-text available
Decreased upper-extremity/visuomotor abilities are frequently encountered in healthy aging. However, few studies have assessed hand movements in the prodromal stage of dementia. The evaluation of visuomotor skills in patients with Mild Cognitive Impairment (PwMCI) may have non-negligible clinical relevance both in diagnostic and prognostic terms, given the strong relationships with executive functioning and functional autonomies. In the present review paper, these issues will be disclosed by describing general pathophysiological and neuropsychological mechanisms responsible for visuomotor deficits, and by reporting the available experimental results on differences in visuomotor functioning between PwMCI, healthy controls and/or patients with dementia. Moreover, the relationships binding visuomotor and executive domains to functional autonomies will be then addressed. Finally, we will propose insights for future research.
... Dans la maladie d'Alzheimer, il a été rapporté récemment que l'avancée de la maladie pourrait affecter les fonctions motrices , en plus des fonctions instrumentales impliquées dans les activités quotidiennes (Yan, Rountree, Massman, Doody, & Li, 2008;de Paula et al., 2016). Par exemple, les personnes atteintes de la maladie d'Alzheimer présentent des temps de réaction plus longs dans une tâche de tapping par comparaison à des personnes n'ayant pas de trouble cognitif . ...
... Par conséquent, une comparaison entre les deux activités devrait être réalisée avec une même personne afin de confirmer l'impact de la musique sur les EFE par comparaison à l'interaction sociale sans musique. Le placement en maison de repos est en effet souvent associé à une sévérité plus importante de la maladie (Smith et al., 2000;Toot, Swinson, Devine, Challis, & Orrell, 2017) incluant notamment un déclin des fonctions instrumentales et motrices (Yan, Rountree, Massman, Doody, & Li, 2008;de Paula et al., 2016) et une augmentation des troubles de l'humeur (Yaffe et al., 2002;Cerejeira, Lagarto, & Mukaetova-Ladinska, 2012). Bien que le score de MMSE ne diffère pas entre les groupes dans cette comparaison, l'impact de la maladie à ce niveau chez les personnes vivant en maison de repos pourrait entraîner une possible différence des réponses comportementales entre les deux groupes. ...
... En effet, le placement en maison de repos dans le cadre d'une maladie d'Alzheimer est souvent associé à l'aggravation des symptômes liés à la progression de la maladie. Les symptômes se traduisent notamment par une réduction des capacités instrumentales qui conduit à une perte de l'autonomie (Yan et al., 2008;de Paula et al., 2016). Bien que nos groupes soient appariés au niveau du score MMSE, il se peut que les fonctions instrumentales soient déficitaires et que ces difficultés aient affecté la précision de la synchronisation. ...
Dans les interventions musicales réalisées auprès de personnes atteintes de la maladie d’Alzheimer ou de maladies apparentées, il est fréquemment demandé aux participants de bouger au rythme de la musique. La synchronisation au rythme musical, particulièrement en groupe, implique des réponses à différents niveaux (moteur, rythmique, social et émotionnel) et pourrait procurer du plaisir ainsi que renforcer les liens sociaux des patients et de leur entourage. Cependant, la synchronisation au rythme de la musique et le lien qui pourrait exister entre ces différents niveaux de la réponse à cette activité sont peu connus dans la maladie d’Alzheimer. L’objectif de cette thèse est d’examiner les différents aspects du comportement des personnes avec une maladie d’Alzheimer (ou maladies apparentées) et des participants avec un vieillissement physiologique ‘normal’ au cours d’une activité de synchronisation au rythme musical réalisée en action conjointe avec un musicien. L’approche préconisée dans ce travail se base sur une méthode pluridisciplinaire incluant les sciences du mouvement, la psychologie sociale et la neuropsychologie. En premier lieu, nous avons étudié l’effet du contexte social et de la musique (et de ses caractéristiques temporelles) sur les performances de synchronisation et sur l’engagement social, émotionnel, rythmique et moteur de personnes atteintes de la maladie d’Alzheimer dans cette activité (étude 1 chapitre 4 et 5). Les résultats ont montré que la présence physique d’une chanteuse réalisant la tâche de synchronisation avec le participant modulait différemment les performances de synchronisation et la qualité de la relation sociale et émotionnelle par comparaison à un enregistrement audio-visuel de cette chanteuse. Cet effet du contexte social était d’ailleurs plus important en réponse à la musique qu’au métronome et était modulé par le tempo et la métrique. De plus, nous avons trouvé que la musique augmentait l’engagement rythmique des participants par comparaison au métronome. Ensuite, nous avons comparé les réponses à la tâche de synchronisation dans le vieillissement pathologique et physiologique (étude 2 chapitre 6 et 7). Les résultats ont révélé que les performances de synchronisation ne différaient pas entre les deux groupes suggérant une préservation du couplage audio-moteur dans la maladie d’Alzheimer à travers cette tâche. Bien que la maladie réduisait l’engagement moteur, social et émotionnel en réponse à la musique par comparaison au vieillissement physiologique, un effet du contexte social était observé sur le comportement dans les deux groupes. Enfin, nous avons comparé les groupes de participants atteints de la maladie d’Alzheimer entre les deux études montrant que la sévérité de la maladie pouvait altérer la synchronisation et l’engagement dans l’activité (chapitre 8). En conclusion, ce travail de thèse a mis en évidence que le couplage audio-moteur est en partie préservé chez les personnes atteintes de la maladie d’Alzheimer et que l’action conjointe avec un partenaire module la qualité de la relation sociale ainsi que l’engagement à la musique. Les connaissances théoriques acquises par ce travail permettent de mieux comprendre l’évolution des comportements en réponse à la musique dans la maladie d’Alzheimer. La méthode mise au point par cette thèse offre ainsi l’opportunité d’évaluer les bénéfices thérapeutiques des interventions musicales à différents niveaux sur le comportement des personnes avec une maladie d’Alzheimer. De telles perspectives permettraient d’améliorer la prise en charge de ces personnes et de leurs aidants.
... A mild decline in fine hand motor function and complex hand motor function were found in older adults and affected to less able to control or adjust the amount force to fit the task, which is essential for activities of daily living (ADL) such as pouring milk, removing money from a wallet, and writing. Especially, hand dexterity is an important component to completely perform the tasks in ADL and the hand dexterity showed a decrease in older adults with MCI [5][6][7][8][9]. Changes in brain from neurodegenerative dementia (e.g., brain atrophy, neuronal loss, or synaptic dysfunction) lead to difficulty to learn movement causing both cognitive and motor dysfunction in MCI [10]. ...
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Background/aims: Many motor impairments are present in older adults with cognitive decline. One of them is the impairment of hand dexterity and bimanual coordination that result in poor functional ability in the activities of daily living (ADL). This study investigated the effects of hand dexterity and bimanual coordination declination on the sub-domains of ADL in older adults with mild cognitive impairment (MCI). Methods: Thirty-one senior individuals with MCI were recruited in this study. The Purdue Pegboard Test was used to measure hand dexterity, and bimanual coordination was assessed by the continuous circle-drawing task. Their ADL were assessed with the General Activity Daily Living questionnaire. Results: The correlations analysis showed an association between the dominant hand and bimanual dexterity with the domestic domain of ADL and all conditions of hand dexterity with the complex domain of ADL. Moreover, the multiple regression analysis showed that the predictor of the greatest effect for domestic and complex domains was dominant hand dexterity. Discussion/conclusion: These results revealed that dominant hand dexterity strongly affected domestic and complex ADL in older adults with MCI. There were age-related changes regarding lateral asymmetrical motor reduction, especially in cognitive tasks. However, complex tasks involving cognitive function may need dominant, nondominant and bimanual hand dexterity.
... A substantial body of literature demonstrates an association between functional self-care capabilities and cognitive function [79][80][81]. In parallel with such reports, declined motor function is reported in persons with CI [82,83]. Motor impairments in persons with CI may be due to both: (1) declined capacity of attentional resources, and (2) increased attentional demands in voluntary movements. ...
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While patients with heart failure experience a wide range of symptoms, evidence is mounting that patients with heart failure suffer from reduced functional independence. Given that the number of patients with heart failure is rising and considering the adverse outcomes of reduced functional independence, understanding the underlying mechanisms of reduced functionality in patients with heart failure is of increasing importance. Yet, little information exists on how heart failure negatively affects functional independence, including motor function. This article summarizes reports of reduced independence and highlights its significant adverse outcomes in the patients with heart failure. Finally, this article discusses potential causes of reduced independence based on existing reports of impaired central and peripheral nervous systems in the patients with heart failure. Overall, the article provides a solid foundation for future studies investigating motor impairments in patients with heart failure. Such studies may lead to advances in treatment and prevention of reduced independence associated with heart failure, which ultimately contribute to the well-being of patients with heart failure.
Background: Despite the prevalence of motor symptoms in mild cognitive impairment (MCI) and Alzheimer’s disease (AD), their underlying neural mechanisms have not been thoroughly studied. Objective: This review summarizes the neural underpinnings of motor deficits in MCI and AD. Methods: We searched PubMed up until August of 2021 and identified 37 articles on neuroimaging of motor function in MCI and AD. Study bias was evaluated based on sample size, availability of control samples, and definition of the study population in terms of diagnosis. Results: The majority of studies investigated gait, showing that slower gait was associated with smaller hippocampal volume and prefrontal deactivation. Less prefrontal activation was also observed during cognitive-motor dual tasking, while more activation in cerebellar, cingulate, cuneal, somatosensory, and fusiform brain regions was observed when performing a hand squeezing task. Excessive subcortical white matter lesions in AD were associated with more signs of parkinsonism, poorer performance during a cognitive and motor dual task, and poorer functional mobility. Gait and cognitive dual-tasking was furthermore associated with cortical thickness of temporal lobe regions. Most non-gait motor measures were only reported in one study in relation to neural measures. Conclusion: Cross-sectional designs, lack of control groups, mixing amnestic- and non-amnestic MCI, disregard of sex differences, and small sample sizes limited the interpretation of several studies, which needs to be addressed in future research to progress the field.
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The unmet timely diagnosis requirements, that take place years after substantial neural loss and neuroperturbations in neuropsychiatric disorders, affirm the dire need for biomarkers with proven efficacy. In Parkinson’s disease (PD), Mild Cognitive impairment (MCI), Alzheimers disease (AD) and psychiatric disorders, it is difficult to detect early symptoms given their mild nature. We hypothesize that employing fine motor patterns, derived from natural interactions with keyboards, also knwon as keystroke dynamics, could translate classic finger dexterity tests from clinics to populations in-the-wild for timely diagnosis, yet, further evidence is required to prove this efficiency. We have searched PubMED, Medline, IEEEXplore, EBSCO and Web of Science for eligible diagnostic accuracy studies employing keystroke dynamics as an index test for the detection of neuropsychiatric disorders as the main target condition. We evaluated the diagnostic performance of keystroke dynamics across 41 studies published between 2014 and March 2022, comprising 3791 PD patients, 254 MCI patients, and 374 psychiatric disease patients. Of these, 25 studies were included in univariate random-effect meta-analysis models for diagnostic performance assessment. Pooled sensitivity and specificity are 0.86 (95% Confidence Interval (CI) 0.82–0.90, I ² = 79.49%) and 0.83 (CI 0.79–0.87, I ² = 83.45%) for PD, 0.83 (95% CI 0.65–1.00, I ² = 79.10%) and 0.87 (95% CI 0.80–0.93, I ² = 0%) for psychomotor impairment, and 0.85 (95% CI 0.74–0.96, I ² = 50.39%) and 0.82 (95% CI 0.70–0.94, I ² = 87.73%) for MCI and early AD, respectively. Our subgroup analyses conveyed the diagnosis efficiency of keystroke dynamics for naturalistic self-reported data, and the promising performance of multimodal analysis of naturalistic behavioral data and deep learning methods in detecting disease-induced phenotypes. The meta-regression models showed the increase in diagnostic accuracy and fine motor impairment severity index with age and disease duration for PD and MCI. The risk of bias, based on the QUADAS-2 tool, is deemed low to moderate and overall, we rated the quality of evidence to be moderate. We conveyed the feasibility of keystroke dynamics as digital biomarkers for fine motor decline in naturalistic environments. Future work to evaluate their performance for longitudinal disease monitoring and therapeutic implications is yet to be performed. We eventually propose a partnership strategy based on a “co-creation” approach that stems from mechanistic explanations of patients’ characteristics derived from data obtained in-clinics and under ecologically valid settings. The protocol of this systematic review and meta-analysis is registered in PROSPERO; identifier CRD42021278707. The presented work is supported by the KU-KAIST joint research center.
Background: The Montreal Cognitive Assessment (MoCA) is a standard test for screening and monitoring cognitive functions. Objective: This study explored the two-year changes in MoCA scores in older adults. Methods: Fifty-seven participants with mild cognitive impairment (MCI) and 87 participants with normal cognition completed the baseline and two-year follow-up assessments. Apart from MoCA, tests on visuospatial judgment, memory, and motor-related executive function were administered. Results: The results identified three MCI subgroups based on the differential changes in MoCA scores. They were the consistently low, consistently high, and low-to-high between-time performances. These heterogeneous test performances are on contrary to the significant deteriorations in executive function and finger dexterity across all subgroups. Repeated exposure to MoCA tests during the follow-up period was found to be a plausible indicator of the MCI subgroup categorization. Conclusion: Findings raise concerns over adopting brief clinical instrument for repeated testing, such as MoCA, for monitoring MCI conditions among older adults. Fulltext access:
Purpose Cowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning. Methods This monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified. Results Fifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman’s facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%). Conclusion Altered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum.
Background: As the global aging population is rapidly advancing, recognizing the full potential of periodontal disease (PD) in the onset or progression of Alzheimer's disease (AD) is important for reducing geriatric morbidity. This review explores the possible role of PD in the pathogenesis of AD, as the pathological mechanisms underlying AD are the most well-studied among all types of dementia. The investigation was conducted using the electronic academic databases PubMed and ScienceDirect, employing a combination of keywords "periodontal disease," "periodontitis," "Alzheimer's disease," "dementia," and "Porphyromonas gingivalis." After applying the selection and eligibility criteria and removing overlaps, from an initial search finding of 5,933 studies, 11 were finally included for qualitative analysis. Highlight: The inflammatory reaction induced by oral pathogenic bacteria related to PD, through complex pathways, may exacerbate inflammation in the central nervous system, thereby contributing to the progression of AD. Conclusion: Maintenance of adequate oral hygiene in patients diagnosed with AD is significant because they suffer from a gradual loss of manual dexterity as the disease advances. Additionally, the evidence presents the potential of systemic inflammation from PD-induced pathogenic bacteria, illustrating the grave cyclical progression of AD.
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Cognitive functioning influences activities of daily living (ADL). However, studies reporting the association between ADL and neuropsychological performance show inconsistent results regarding what specific cognitive domains are related to each specific functional domains. Additionally, whether depressive symptoms are associated with a worse functional performance in older adults is still under explored. We investigated if specific cognitive domains and depressive symptoms would affect different aspects of ADL. Participants were 274 older adults (96 normal aging participants, 85 patients with mild cognitive impairment, and 93 patients probable with mild Alzheimer's disease dementia) with low formal education (∼4 years). Measures of ADL included three complexity levels: Self-care, Instrumental-Domestic, and Instrumental-Complex. The specific cognitive functions were evaluated through a factorial strategy resulting in four cognitive domains: Executive Functions, Language/Semantic Memory, Episodic Memory, and Visuospatial Abilities. The Geriatric Depression Scale measured depressive symptoms. Multiple linear regression analysis showed executive functions and episodic memory as significant predictors of Instrumental-Domestic ADL, and executive functions, episodic memory and language/semantic memory as predictors of Instrumental-Complex ADL (22 and 28% of explained variance, respectively). Ordinal regression analysis showed the influence of specific cognitive functions and depressive symptoms on each one of the instrumental ADL. We observed a heterogeneous pattern of association with explained variance ranging from 22 to 38%. Different instrumental ADL had specific cognitive predictors and depressive symptoms were predictive of ADL involving social contact. Our results suggest a specific pattern of influence depending on the specific instrumental daily living activity.
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Background: Decline in cognitive performance is associated with gait deterioration. Our objectives were: 1) to determine, from an original study in older community-dwellers without diagnosis of dementia, which gait parameters, among slower gait speed, higher stride time variability (STV) and Timed Up & Go test (TUG) delta time, were most strongly associated with lower performance in two cognitive domains (i.e., episodic memory and executive function); and 2) to quantitatively synthesize, with a systematic review and meta-analysis, the association between gait performance and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). Methods: Based on a cross-sectional design, 934 older community-dwellers without dementia (mean±standard deviation, 70.3±4.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental State Examination defined low episodic memory performance. Low executive performance was defined by clock-drawing test errors. STV and gait speed were measured using GAITRite system. TUG delta time was calculated as the difference between the times needed to perform and to imagine the TUG. Then, a systematic Medline search was conducted in November 2013 using the Medical Subject Heading terms "Delirium," "Dementia," "Amnestic," "Cognitive disorders" combined with "Gait" OR "Gait disorders, Neurologic" and "Variability." Findings: A total of 294 (31.5%) participants presented decline in cognitive performance. Higher STV, higher TUG delta time, and slower gait speed were associated with decline in episodic memory and executive performances (all P-values <0.001). The highest magnitude of association was found for higher STV (effect size = -0.74 [95% Confidence Interval (CI): -1.05;-0.43], among participants combining of decline in episodic memory and in executive performances). Meta-analysis underscored that higher STV represented a gait biomarker in patients with MCI (effect size = 0.48 [95% CI: 0.30;0.65]) and dementia (effect size = 1.06 [95% CI: 0.40;1.72]). Conclusion: Higher STV appears to be a motor phenotype of cognitive decline.
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Objective: To propose and evaluate the psychometric properties of a multidimensional measure of activities of daily living (ADLs) based on the Katz and Lawton indices for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: In this study, 85 patients with MCI and 93 with AD, stratified by age (≤ 74 years, > 74 years), completed the Mini Mental State Examination (MMSE) and the Geriatric Depression Scale, and their caregivers completed scales for ADLs. Construct validity (factor analysis), reliability (internal consistency), and criterion-related validity (receiver operating characteristic analysis and logistic regression) were assessed. Results: Three factors of ADL (self-care, domestic activities, and complex activities) were identified and used for item reorganization and for the creation of a new inventory, called the General Activities of Daily Living Scale (GADL). The components showed good internal consistency (> 0.800) and moderate (younger participants) or high (older participants) accuracy for the distinction between MCI and AD. An additive effect was found between the GADL complex ADLs and global ADLs with the MMSE for the correct classification of younger patients. Conclusion: The GADL showed evidence of validity and reliability for the Brazilian elderly population. It may also play an important role in the differential diagnosis of MCI and AD.
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The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.
Purpose The purpose of this study was to examine the relationship between balance control and cognitive functions, gait speed, and activities of daily living. Sample In all, 80 elderly participants with mild cognitive impairment (mean age 67.07 ± 4.3 years) were randomly allocated into the experimental group (n = 40) or the control group (n = 40). Methods Balance control was evaluated by the Balance Evaluation Systems Test (BESTest). Cognitive functions were evaluated by the Trail Making Test and the Nine Hole Peg Test. Gait speed was assessed by the Up and Go test with and without dual task. For evaluation of activities of daily living (ADL), the BADLS test was used. The experimental group underwent CogniPlus 20 training sessions twice a week. Both groups had 30 min of physical training daily for 10 weeks. Results After training, there were five significant correlations found in the experimental group (balance control and visuomotor coordination, psychomotor speed, gait speed with and without cognitive tasks, and activities of daily living). In the control group, one significant correlation was found between balance control and gait speed. Conclusion The cognitive-motor training performed for 10 weeks confirmed more significant relationships between balance control, cognitive functions, gait speed, and activities of daily living, when compared with motor intervention alone.
Introduction: Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow-up. Methods: In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini-mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL). Results: Dementia cases first reported memory complaints 16 years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas APOE-ε4 carriers declined less in daily functioning. Discussion: These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline.
Objectives: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD). Method: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment. Results: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis. Conclusion: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.
Background: We studied the suitability of The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) total score for monitoring Alzheimer's disease (AD) progression in early-diagnosed medicated patients. We also investigated possible differences in progression between patients with very mild or mild baseline AD. Methods: In this three-year follow-up of 115 ALSOVA study patients with clinical dementia ratings (CDR) of very mild (0.5) or mild (1) AD, we analyzed total CERAD-NB, Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory, and Clinical Dementia Rating Sum of Boxes scores. Correlations were identified with efficacy parameters. Results: Over three years, total CERAD-NB declined significantly in both groups. Annual change rates of total CERAD-NB were also significant. Total CERAD-NB revealed annual differences in cognition between study groups, while MMSE did not. Total CERAD-NB correlated well with other cognitive and global measures, but not with NPI. For almost two years, the CDR-0.5 group maintained a higher activities of daily living than the CDR-1 group exhibited at baseline. Furthermore, the CDR-0.5 group showed milder neuropsychiatric symptoms at the end of follow-up than the CDR-1 group showed at baseline. Conclusions: The CERAD total score is a suitable and sensitive follow-up tool in longitudinal AD trials. Cognition progression rates did not significantly differ between study groups; however, patients with very mild AD at baseline had milder neuropsychiatric symptoms after long-term follow-up. This emphasizes the importance of early diagnosis and assessment of neuropsychiatric symptoms at the diagnostic visit and during follow-up.