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Functional impairment as a defining feature of: Amnestic MCI cognitive, emotional, and demographic correlates

  • Reintegra: Centro de Rehabilitación Neurológica

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Early definitions of mild cognitive impairment (MCI) excluded the presence of functional impairment, with preservation of a person's ability to perform activities of daily living (ADL) as a diagnostic criterion. However, recent studies have reported varying degrees of functional impairment associated with MCI. Hence, we aimed to test the potential functional impairment associated with MCI and its predictors. Sixty-nine healthy elderly subjects, 115 amnestic single-domain MCI subjects (a-MCI), and 111 amnestic multi-domain MCI subjects (md-MCI) were assessed using a battery of neuropsychological tests including measures of attention, memory, working memory, executive functions, language, and depression. Additionally, functional ability was assessed by both qualitative (WHO-DAS II) and quantitative (CHART) instruments. Cognitive and functional performance was compared between groups, and regression analyses were performed to identify predictors of functional ability. The md-MCI group was more impaired than the a-MCI group, and both were more impaired than healthy subjects in all cognitive measures, in total CHART score, CHART cognitive and mobility subscores, and WHO-DAS II communication and participation subscales. For the rest of the functional measures, the md-MCI group was more impaired than healthy controls. Prediction of functional ability by cognitive measures was limited to md-MCI subjects and was higher for the CHART than for the WHO-DAS II. The WHO-DAS II was largely influenced by depressive symptoms. Functional impairment is a defining feature of MCI and is partially dependent on the degree of cognitive impairment. Quantitative measures of functional ability seem more sensitive to functional impairment in MCI than qualitative measures, which seem to be more related to depression.
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International Psychogeriatrics (2012), 24:9, 1494–1504 C
International Psychogeriatric Association 2012
Functional impairment as a defining feature of: amnestic MCI
cognitive, emotional, and demographic correlates
Igor Bombin,1,2 Sandra Santiago-Ramajo,3Maite Garolera,5Eva M. Vega-González,1
Noemí Cerulla,4,6 Alfonso Caracuel,3Alicia Cifuentes,1M. Teresa Bascarán7and
Julio Bobes7
1Reintegra Foundation, Oviedo, Spain
2Department of Psychology, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, University of Oviedo, Oviedo, Spain
3Department of Personality Evaluation and Treatment Psychology, University of Granada, Granada, Spain
4Neuropsychology Unit Hospital de Terrassa-Consorci Sanitari de Terrassa, Barcelona, Spain
5Grup de Recerca Consolidat de Neuropsicologia (SRG0941), University of Barcelona, Spain
6Sant Jordi Day Hospital for Cognitive impairment-Consorci Sanitari de Terrassa, Barcelona, Spain
7Department of Medicine, Psychiatry Area, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, University of Oviedo, Oviedo, Spain
Background: Early definitions of mild cognitive impairment (MCI) excluded the presence of functional
impairment, with preservation of a person’s ability to perform activities of daily living (ADL) as a diagnostic
criterion. However, recent studies have reported varying degrees of functional impairment associated
with MCI. Hence, we aimed to test the potential functional impairment associated with MCI and its
Methods: Sixty-nine healthy elderly subjects, 115 amnestic single-domain MCI subjects (a-MCI), and 111
amnestic multi-domain MCI subjects (md-MCI) were assessed using a battery of neuropsychological tests
including measures of attention, memory, working memory, executive functions, language, and depression.
Additionally, functional ability was assessed by both qualitative (WHO-DAS II) and quantitative (CHART)
instruments. Cognitive and functional performance was compared between groups, and regression analyses
were performed to identify predictors of functional ability.
Results: The md-MCI group was more impaired than the a-MCI group, and both were more impaired than
healthy subjects in all cognitive measures, in total CHART score, CHART cognitive and mobility subscores,
and WHO-DAS II communication and participation subscales. For the rest of the functional measures,
the md-MCI group was more impaired than healthy controls. Prediction of functional ability by cognitive
measures was limited to md-MCI subjects and was higher for the CHART than for the WHO-DAS II. The
WHO-DAS II was largely influenced by depressive symptoms.
Conclusions: Functional impairment is a defining feature of MCI and is partially dependent on the degree
of cognitive impairment. Quantitative measures of functional ability seem more sensitive to functional
impairment in MCI than qualitative measures, which seem to be more related to depression.
Key words: mild cognitive impairment (MCI), disability, functional independence, cognition, healthy elderly, WHODAS-II, CHART, neuropsychology
Since the early descriptions of mild cognitive
impairment (MCI) (Petersen et al., 1999), there has
been increasing interest in its clinical characteriza-
tion and prognosis (Nelson and O’Connor, 2008;
Correspondence should be addressed to: Dr. Igor Bombin, PhD, Reintegra
Foundation, Centro de Rehabilitación Neurológica, C/ Eduardo de Fraga
Torrejón, 4, bajo, Oviedo. 33011 Spain. Phone: +34 984 08 48 46; Fax: +34
984 08 48 41. Email: Received 26 Jul 2011; revision
requested 16 Sep 2011; revised version received 2 Mar 2012; accepted 5 Mar
2012. First published online 19 April 2012.
Werner and Korczyn, 2008). In previous reports
(Petersen et al., 1999), subjects with MCI exhibit
poorer cognitive functioning than healthy subjects,
but not as impaired as patients with dementia.
Prognosis studies have stressed the use of this
nosological entity as a risk or prodromic state for
dementia, due to the high rate of conversion of
MCI subjects to dementia (10%–15% of patients
who meet the criteria of amnestic MCI develop
Alzheimer’s-type dementia per year, up to 80% at
5-year follow-up) (Amieva et al., 2004; Petersen,
2004; Gauthier et al., 2006). Approximately 16% of
Functional impairment as MCI defining feature 1495
the populations of older people who have not been
diagnosed with dementia meet the current criteria
for MCI (Petersen et al., 2010) and MCI prevalence
increases with age.
Dementia inevitably involves a loss of functional
independence, resulting in a progressive increase
in disability (Sauvaget et al., 2002). In parallel
with the progressive loss of personal autonomy,
increases in family/caregiver burden and in demand
for health and social resource use have been
reported (Potkin, 2002). However, disability, a
milder form than dementia, is not included as
an MCI diagnostic criterion. Furthermore, the
diagnosis of MCI requires preservation of the
person’s ability to perform activities of daily
living (ADL) (Petersen et al, 1999; Petersen
and Negash, 2008), “or at least that impairment
is minimal” in complex instrumental functions
(Winblad et al., 2004). Recently, the lack of
functional impairments of MCI in daily living
as a diagnostic criterion has been questioned as
the result of studies pointing to impairment in
instrumental ADL rather than basic ADL (Tam
et al., 2007; Pereira et al., 2008; Ahn et al., 2009;
Burton et al., 2009; Schmitter-Edgecombe et al.,
2009; Aretouli and Brandt, 2010; Bangen et al.,
2010; Reppermund et al., 2010; Teng et al., 2010a;
2010b). Although these studies were carried out in
different countries and used different instruments
to assess impairments in ADL, they all suggest that
people who meet the other criteria described for
MCI do show functional impairment of ADL.
Disability in dementia and other neurological
and neuropsychiatric disorders has been largely
associated, and partially attributed, to cognitive
impairment (e.g. Millis et al., 1994 in brain injury;
Green, 1996 in schizophrenia). Those findings
seem to support the apriorihypothesis that MCI
would show some degree of functional impairment,
which could be at least partially predicted by
the cognitive impairment that characterizes MCI.
However, to date there are very few studies that
assess the potential associations between functional
performance and cognitive impairment in MCI
subjects or that attempt to determine which
cognitive areas are more likely to predict functional
abilities in MCI subjects.
In light of the above, we aimed to (1)
determine whether MCI is associated with
functional impairment; (2) identify the role
of sociodemographic, emotional, and cognitive
variables as independent predictors of functional
impairment in elderly healthy subjects, single-
domain amnestic MCI subjects and multi-domain
amnestic MCI subjects; and (3) discuss the extent
to which the two former issues are instrument-
dependent. We hypothesized that (1) MCI patients
will show impaired independent functioning; (2)
among subjects with MCI, such impairment will be
associated with the degree of cognitive impairment,
and to a lower degree with sociodemographic
and anxiety-depression symptoms, whereas in
healthy controls, impaired functioning will be only
associated with sociodemographic and anxiety-
depression symptoms; and (3) in MCI subjects the
degree of impairment and the nature and effect
size of associations will partially depend on the
type of independent functioning, in such a way that
quantitative measures based on performance (Craig
Handicap Assessment and Reporting Technique,
CHART) will be more reliable than qualitative
measures (World Health Organization Disability
Assessment Schedule, second version, WHO-DAS-
II) based on a subjective judgment of disability.
Recruitment of participants was conducted during
2010 and the beginning of 2011 in three
clinical or university settings in three regions
of Spain: the University of Oviedo (northern
Spain), Consorci Sanitari of Terrassa (Barcelona,
northeastern Spain), and the University of Granada
(southern Spain). Recruitment in the Consorci
Sanitari of Terrassa was done by review of clinical
history and application of inclusion and exclusion
criteria to outpatients attending its memory clinic.
The two universities recruited participants by
inviting subjects attending community services
for healthy elderly people to participate in
a free memory-training program. The memory
training program was conducted as part of a
randomized clinical trial, aimed to compare the
efficacy of two neuropsychological rehabilitation
strategies (restitution versus compensation and
substitution) in improving functional independence
and cognition in MCI subjects.
A total of 328 elderly people living in
the community were recruited. Inclusion criteria
included: age over 55 years, meeting the diagnostic
criteria for MCI as defined in Petersen et al.
(1999), living in the community, and signing
informed consent. Exclusion criteria were: living in
an assisted living residence, cognitive functioning
suggesting a possible diagnosis of dementia (see
below), previous diagnosis of dementia, previous
psychiatric disorder according to DSM-IV-TR at
the time of recruitment, presenting a moderate or
higher degree of disability due to other conditions
than MCI, and severe language impairments that
would compromise their active participation in the
neuropsychological rehabilitation clinical trial.
1496 I. Bombin et al.
Neuropsychological assessment
Cognitive assessment was performed by means
of a neuropsychological battery designed to com-
prehensively evaluate attention, working memory,
memory, executive functioning, and language (see
Table 1). In order to obtain a summary score
for each cognitive domain (mean of variables that
compounded a cognitive domain as presented in
Table 1) and a global score for cognition (average
of the four cognitive domains), raw test scores
were converted to T-scores (mean =50, SD =
10) based on normative data published in the
Spanish handbooks of the tests (WAIS-III digits,
Stroop) and normative data obtained in an ongoing
normative study with an independent healthy
sample (N=173). In this ongoing normative study,
normative data were obtained for the following
age groups: 56–65 years (n=56), 66–75 (n=
71), 76 or older (n=46). T-scores were truncated
at 10 (–4 standard deviations), to avoid outlying
values (as suggested in Rousseeuw and Leroy,
1987). Results are reported for cognitive areas
summary scores, in order to avoid an excess
of data (results of single test variables available
upon request). Language summary score was not
included in statistical analyses because none of the
recruited subjects showed language impairment and
distribution of this variable was very asymmetric due
to ceiling effect of the language measures employed.
Neuropsychological assessment was performed by
seven experienced neuropsychologists. Reliability in
administering and scoring the neuropsychological
tests were evaluated prior to baseline estimation in
an independent sample of ten subjects (inter-rater
reliability exceeded 0.80 for all instruments).
Memory complaints were registered by means of
the Spanish version (García Martínez and Sánchez
Cánovas, 1994) of the Memory Failures Everyday
(MFE) test (Sunderland et al., 1984), a 28-item
questionnaire about experiences in daily living
associated with memory and other cognitive area
failures. It is scored according to a 3-point likert-
scale about the frequency of such failure (0 =never
or almost never; 1 =sometimes or rarely; 2 =many
Sample subdivision
Based on the results of neuropsychological
assessment, the sample was divided in six groups:
healthy subjects (control group); subjects with
single domain amnestic MCI (a-MCI); subjects
with multi-domain amnestic MCI (md-MCI);
single non-amnestic MCI; multi-domain non-
amnestic MCI; and subjects with a dementia-like
cognitive functioning. Sample sociodemographic
and clinical characteristics of the groups are
described in Table 2. The classification of
Table 1. Neuropsychological tests and variables
grouped by cognitive domain
Attention WAIS-III digits forward
Time to complete TMT-A
Number of correct items
stroop 1 words
Number of correct items
stroop 2 colors
Working memory WAIS-III digits backward
Time to complete TMT-B
Learning and memory HVLT total learning
HVLT long term free recall
HVLT discrimination
Executive functions Number of words on
Number of words on verbal
fluency (animals)
Stroop interference score
BADS key search test
Language Token test (comprehension)
Boston naming test (30 items)
WAIS-III =Wechsler Adult Intelligence Scale, 3rd Edition;
TMT-A =Trail Making Test, part A; TMT-B =Trail
Making Test, part B; HVLT =Hopkins Verbal Learning Test;
COWAT =Control Oral Word Association Test. Total phonetic
cueing (F+A+S); BADS =Behavioral Assessment of the
Dysexecutive Syndrome.
subjects to different groups was made according to
performance in four cognitive domains (attention,
memory, working memory, and executive function):
Healthy Group (HG; n=69):
subjects who, after neuropsychological
assessment, presented a performance
within normal limits. A cutoff point
of T-score equal or higher than 40
(z ≥−1 SD) in all the four cognitive
domains was established. All healthy
subjects were recruited at the above
cited community services for healthy
Subjects with MCI (n=238): subjects
with at least one cognitive domain
summary T-score equal to or below 35
(z≤−1.5), but whose possible dia-
gnosis of dementia was not supported.
This group was subdivided into four
subgroups, according to the four types
of MCI proposed by Petersen et al.
- Amnestic Single-domain MCI Group
(a-MCI; n=115): subjects whose
T-score in the cognitive domain of
memory or in the long-term free-recall
of the Hopkins Verbal Learning Test
Functional impairment as MCI defining feature 1497
Table 2. Comparison of demographic, emotional, neuropsychological, and functional variables between healthy and MCI subjects
N=69 N =226 χ2N=115 N =111 χ2(p<0.05)
Demographic variables: Mean/SD Mean/SD pMean/SD Mean/SD p
- Age 70.10/8.5 73.50/8.4 0.004 71.79/8.3 75.27/8.2 <0.001 HG and a-MCI <md-MCI
- Education (years) 9.15/4.5 6.82/3.7 <0.001 8.01/3.7 5.61/3.2 <0.001 HG and a-MCI >md-MCI
- Gender: % Female 78.3% 68.6% 0.122 69.6% 67.6% 0.286
- Type of residence:
Rural 36.2% 38.2% 0.948 38.6% 37.8% 0.991
Urban 60.9% 58.7% 58.8% 58.6%
Semi-urban 2.9% 3.1% 2.6% 3.6%
Subjective memory complaints Mean/SD Mean/SD T Student Mean/SD Mean/SD ANOVA post hoc Bonferroni1(p<0.05)
MFE 13.85/8.5 20.68/11.6 <0.001 18.56/10.02 22.90/12.82 <0.001 HG <a-MCI <md-MCI
Emotional status Mean/SD Mean/SD T Student Mean/SD Mean/SD ANOVA
- GDS 9.57/5.9 10.72/6.3 NS 9.56/5.7 12.03/6.6 0.008 HG and a-MCI <md-MCI
Neuropsychological functioning: Mean/SD Mean/SD Mean/SD Mean/SD MANCOVA post hoc Bonferroni2(p<0.05)
- Attention 51.64/6.4 41.52/8.9 <0.001 47.26/5.8 35.57/7.6 <0.001 HG >a-MCI >md-MCI
- Memory 50.77/6.9 31.69/7.2 <0.001 34.54/6.5 28.74/6.8 <0.001 HG >a-MCI >md-MCI
- Working memory 52.91/7.7 39.44/11.2 <0.001 48.30/6.0 30.25/7.2 <0.001 HG >a-MCI >md-MCI
- Executive function 49.98/6.0 43.61/7.0 <0.001 46.47/6.7 40.56/5.8 <0.001 HG >a-MCI >md-MCI
- Global cognition 51.33/4.9 39.01/6.6 <0.001 44.14/4.2 33.69/4.0 <0.001 HG >a-MCI >md-MCI
Functional independence: Mean/SD Mean/SD Mean/SD Mean/SD MANCOVA post hoc Bonferroni2(p<0.05)
WHODAS II total : 41.82/13.0 51.65/19.0 <0.001 46.42/14.3 57.16/21.7 <0.001 HG and a-MCI <md-MCI
- Communication 8.34/3.7 10.92/4.8 0.001 9.79/3.5 12.11/5.7 <0.001 HG <a-MCI <md-MCI
- Mobility 6.89/3.3 8.60/4.3 <0.001 7.89/3.8 9.34/4.6 <0.001 HG <md-MCI
- Self- care 4.17/0.8 5.29/2.7 <0.001 4.71/1.7 5.89/3.4 <0.001 HG and a-MCI <md-MCI
- Interpersonal 4.56/1.7 5.58/2.6 <0.001 5.25/2.0 5.94/3.1 0.006 HG <md-MCI
- Life activities 6.68/3.5 8.13/4.7 0.007 6.80/3.6 9.53/5.3 <0.001 HG and a-MCI <md-MCI
- Participation 11.15/4.2 13.11/5.1 0.002 11.96/4.6 14.32/5.4 <0.001 HG and a-MCI <md-MCI
CHART total: 350.42/37.6 303.78/68.0 <0.001 320.46/57.8 286.79/73.4 <0.001 HG >a-MCI >md-MCI
Cognitive 93.82/13.5 75.42/24.3 <0.001 82.15/19.4 68.57/26.9 <0.001 HG >a-MCI >md-MCI
Mobility 97.85/5.5 91.64/12.9 <0.001 93.22/11.8 90.03/13.8 <0.001 HG and a-MCI >md-MCI
Occupation 73.58/24.7 60.70/31.5 0.001 66.76/29.74 54.53/32.3 0.002 HG >md-MCI
Social integration 85.16/20.1 76.00/28.4 0.004 78.32/26.9 73.64/29.9 0.009 HG >md-MCI
Note: GDS =Geriatric Depression Scale; MFE =memory failures everyday; WHODAS II =the World Health Organization Disability Assessment Schedule; SD =Standard Deviation;
CHART =Craig Handicap Assessment and Reporting Technique. HG =Healthy Group; a-MCI =amnestic-MCI group; md-MCI =multidomain-MCI group.
1Bonferroni post hoc test for the ANOVA. 2Bonferroni post hoc test for the MANCOVA after controlling for age, years of education, and GDS score.
1498 I. Bombin et al.
(HVLT) was equal to or below 35 (z
1.5), and the other cognitive domain
summary T-scores above 35 (z >1.5).
- Amnestic multi-domain MCI Group
(md-MCI; n=111): subjects with
T-scores below 35 (z ≤−1.5) in at
least two cognitive domain summary
T-scores, including memory summary
score or long-term free recall of HVLT.
- Non-amnestic single-domain MCI
Group (n=10): subjects with a unique
cognitive domain other than memory
or HVLT long-term free-recall T-score
equaltoorbelow35(z≤−1.5), and
the other cognitive domain summary
T-scores above 35 (z >1.5).
- Non-amnestic multi-domain MCI
Group (n=2): subjects with T-scores
below 35 (z ≤−1.5) in at least two
cognitive domains, other than memory
summary score or long-term free recall
of HVLT.
Given the low sample size of the non-amnestic
single-domain (n=10) and the non-amnestic multi-
domain (n=2) MCI groups, these two groups were
not included in further analyses.
Subjects with a dementia-like cognitive
functioning (n=21): subjects with at
least two cognitive domain summary
T-score below 25 (z<2.5). The
diagnosis of dementia was not proven
due to the lack of neuroimaging
data, but this conservative strategy was
adopted in order to minimize a potential
magnifying effect of differences on func-
tional ability between groups exclusively
due to outliers.
Functional independence assessment
Assessment of functional independence was
performed by means of two different scales, one
based on subjective judgment of disability – the
World Health Organization Disability Assessment
Schedule, second version (WHO-DAS-II) – and
another based on frequency rates of time spent
performing ADL – Craig Handicap Assessment and
Reporting Technique (CHART). The WHO-DAS
II (Federici et al., 2009) is a 36-item inventory
based on the World Health Organization’s
(WHO) International Classification of Functioning,
Disability and Health Framework (WHO-ICF) that
evaluates six domains of functioning in daily life:
understanding and communicating, mobility, self-
care, interpersonal, life activities, and participation
in society. The participants interviewed were
asked to rate the experienced level of “difficulty”
(none, mild, moderate, severe, extreme), by taking
into account the way in which they normally
perform a given activity, and including the use of
whatever support or/and help by a person (aids).
For every item receiving a positive answer, the
subsequent question asks the number of days (“in
thelast30days) in which the interviewee has
found such a difficulty; however, for the present
study only the 36-item answers were analyzed.
A total WHODAS-II functional impairment score
was obtained by adding up all functional areas
subscores, except for the work subscale (possible
total score range: 36–180), higher values indicating
higher degree of functional impairment. The
WHO-DAS II is available at http://www.who.
int/icidh/whodas/whodasversions/36sa.pdf, and ex-
amples of items are “How much difficulty did you
have in: Moving around inside your home? Washing
your whole body? Getting along with people who
are close to you? Taking care of your household
The CHART was designed to provide a simple,
objective measure of the degree of impairments
and disabilities (Whiteneck et al., 1992). Each
CHART dimension is characterized by directly
observable qualities which lend themselves to
easy quantification. CHART consists of six
subscales assessing (1) physical independence; (2)
cognitive independence; (3) mobility / accessibility
to activities and resources inside and outside
the home; (4) occupation, including household
activities, caring activities, volunteer activities,
entertainment, etc.; (5) quantity and quality
of interpersonal relationships, and (6) financial
independence (this subscale was not administered).
For each subscale a percentage score (0%–
100%) is calculated by raw scores conversions
and mathematical operations, indicating a 100%
absolute independence for that domain. A total
CHART functional impairment score was obtained
by adding up all functional areas subscores, except
for the Physical Independence and Economic Self-
Sufficiency subscales (possible total score range: 0–
400), with higher values indicating lower degree of
functional impairment. The Physical Independence
subscore was not included in the summary score
because presence of a moderate or higher degree
of disability due to other conditions than MCI
was an exclusion criterion, so all subjects scored
100. The economic self-sufficiency was excluded
in order to preserve participants’ privacy given
the fact that the fulfillment of this subscale
requires providing data of annual income. The
CHART is available at http://www.craighospital.
org/Research/CHART%20Manual.pdf, and ex-
amples of items are “How many hours per week
do you spend in active homemaking including
parenting, housekeeping, and food preparation?”;
“In a typical week, how many days do you get out
Functional impairment as MCI defining feature 1499
of your house and go somewhere?”; How many
friends... do you visit, phone, or write to at least
once a month?”
Both functional independence scales, which
gather information about both basic and in-
strumental ADL, were administered by trained
neuropsychologists within the context of an
interview in such a way that information was
provided by subjects and a caregiver together when
available, or by subjects alone (some of these
subjects lived alone, or with a spouse with higher
degrees of disability).
Depression symptoms
The presence and severity of depression symptoms
were assessed by the Geriatric Depression Scale
(GDS) (Yesavage, 1988). The GDS is a
screening depression scale for geriatric populations
comprising 30 items to which the subject provides
a “yes” or “no” answer. Each item is scored
as 1 (presence of a depression/anxiety symptom)
or 0 (absence of a depression/anxiety symptom).
According to previous reports, scores ranging 0–10
indicate the absence of depression; 11–20 would
suggest a mild possible depression; and scores
higher than 20 would be suggestive of severe
depression. The GDS was administered by the
neuropsychologists who performed the cognitive
and functional evaluation.
Statistical analyses
Mean and standard deviation are provided
for continuous variables. Discrete variables are
expressed as frequencies and/or percentages.
Distribution of variables was tested by the
Kolmogorov–Smirnov test, and when dividing the
sample into the three subgroups (Healthy, a-MCI,
md-MCI), only the variables of years of education
and WHO-DAS II total score showed non-
normal distributions. On the basis of the normal
distribution of most variables, the sample sizes, the
robustness of the parametric tests based on analysis
of variance, and the need to use post hoc analyses,
these techniques were chosen for statistical analyses.
For sociodemographic data Student’s t-test for
two independent samples (Healthy Group versus
MCI subjects) were used to compare means for
continuous variables. When more than two groups
were considered (for sociodemographic and clinical
data), one-way analysis of variance (ANOVA)
was conducted. When significant differences were
detected the Bonferroni post hoc test was used to
identify which specific groups differed. The χ2
statistics were used for comparison of categorical
measures. As healthy control and MCI groups
differed for age and years of education, the
healthy group differed from the md-MCI group
in age and years of education, analyses on
neuropsychological and functioning variables were
performed controlling for these variables when
required. For doing so, full factorial multivariate
analysis of covariance (MANCOVA) models were
performed, using group (MCI/control and a-
MCI/md-MCI/controls) as fixed factors, cognitive
summary T-scores and WHO-DAS-II and CHART
scores as dependent variables, and age, years of
education, and GDS as covariates. Again, the
Bonferroni post hoc test was performed to identify
specific differences/effects when the MANCOVA
was significant.
Receiver operating characteristic (ROC) curve
analyses were conducted to test diagnostic accuracy
(Healthy vs. all MCI as a group) of the WHO-DAS
II, CHART, MFE, and total cognition variables.
The estimate of the area under the ROC curve was
computed using a binegative exponential model.
Multiple regression analyses were performed
separately with the total sample together and for the
three groups independently (a-MCI, md-MCI, and
controls), with total WHO-DAS II and CHART
scores as dependent variables, and age, years of
education, GDS, and cognitive domain summary
scores as independent variables or predictors.
The step-wise method was used in the regression
analyses due to the fact that it provides a final
model including only significant predictors, which
are presented decreasingly according to the amount
of variance explained.
All statistical analyses were performed with SPSS
v13 (Statistical Package for the Social Sciences,
Chicago, Illinois), and a 2-tailed p-value lower than
0.05 was considered statistically significant.
Differences in demographic and clinical
Comparisons of demographic, cognitive, depression
symptoms, and functional independence variables
are presented in Table 2. Both healthy subjects
and a-MCI were younger and had more years of
education and less depression symptoms than md-
MCI, with no differences in these variables between
the two former groups. Similarly, the md-MCI
group showed higher rates of depression symptoms
than both healthy and a-MCI subjects. Given these
results, for the following comparisons between
the three groups (MANCOVA) age, years of
education, and GDS were introduced as covariates.
MANCOVA analyses results suggested that healthy
subjects had a better cognitive functioning than
both a-MCI and md-MCI in all cognitive areas
1500 I. Bombin et al.
1,0 0,8 0,6 0,4 0,2 0,0
MFE Total
Global Cognition
Figure 1. ROC curve to distinguish normal from the MCI using total CHART, total WHO-DAS II, total MFE, and global cognitive score.
assessed, and that cognitive performance of the a-
MCI group was superior to that of md-MCI in all
cognitive areas. Frequency and severity of subjective
memory complaints followed an identical pattern:
more prominent in md-MCI than in a-MCI, and in
both MCI groups than in healthy subjects.
As to functional independence, the healthy
group showed better functional adjustment than
the MCI group according to both WHO-DAS II
and CHART total scores. When the MCI group
was subdivided into a-MCI and md-MCI, CHART
total score and cognitive domain, and WHO-DAS
II communication subscale showed a similar profile
as cognitive functioning, after controlling for age,
education, and GDS score: md-MCI was more
functionally impaired than a-MCI, showing that
both MCI groups had higher rates of disability than
the healthy group. The md-MCI group showed
a higher degree of functional impairment than
both healthy subjects and a-MCI in the WHO-
DAS II total score and self-care, life activities, and
participation subscales, and in the CHART mobility
domain. The remaining functional ability measures
showed a consistent functional impairment only of
md-MCI in comparison with healthy subjects (for
more details, see Table 2).
In comparing the ROC curves, the CHART
appears with a larger area under the curve (AUC =
0.707) than the WHO-DAS II (AUC =0.347) and
the MFE (AUC =0.331), but less than the global
cognition score (AUC =0.923), and very close to
MMSE (AUC =0.714) (Figure 1).
Predictors of functional status (regression
The results of the regression analyses are shown
in Table 3. When the whole sample was analyzed
together, attention and memory summary scores
explained a total variance of 8.2% and 0.8% of the
WHO-DAS II, respectively, and 9.8% and 1.8%
of the CHART, respectively. When depression
and age were entered in both former models, the
WHO-DAS II score was predicted by depression
symptoms as measured by the GDS (19.2%) and
by executive functions (8.1%) only in the healthy
group. By contrast, CHART total score was only
predicted by age among healthy subjects. For both
MCI groups, WHO-DAS II was predicted by
depression symptoms only, with a total variance
explained of 17.3% for a-MCI and 13.9% for md-
MCI. CHART score was predicted only by age on
a-MCI subjects, and by age, attention, and GDS
score on md-MCI subjects. Attention explained
9.1% variance of CHART total score.
Our results show that functional impairment is a
defining feature of MCI, and that the impairment
Functional impairment as MCI defining feature 1501
Table 3. Regression analyses with total WHO-DAS II and CHART as dependent variables
All subjects together (N=295) WHODAS-II GDS 0.184 58.318 <0.001
Attention 0.266 47.313 <0.001
Age 0.281 34.154 <0.001
Memory 0.289 26.910 <0.001
CHART Age 0.203 65.552 <0.001
Attention 0.301 55.633 <0.001
GDS 0.320 40.931 <0.001
Memory 0.338 33.470 <0.001
Healthy group (n=69) WHODAS-II GDS 0.192 15.301 <0.001
Executive functions 0.273 12.248 <0.001
CHART Age 0.117 8.805 0.004
Amnestic-MCI group (n=115) WHODAS-II GDS 0.173 22.576 <0.001
CHART Age 0.178 22.837 <0.001
Multidomain-MCI group (n=111) WHODAS-II GDS 0.139 15.571 <0.001
CHART Age 0.138 15.722 <0.001
Attention 0.229 14.644 <0.001
GDS 0.271 12.372 <0.001
Method: Step-wise. Independent variables: age, years of education, GDS, attention, memory, working memory and executive functions.
GDS =Geriatric Depression Scale; WHODAS-II =the World Health Organization Disability Assessment Schedule, second edition;
CHART =Craig Handicap Assessment and Reporting Technique; Adj. R2=adjusted R2.
showed by MCI subjects is partially dependent
on the degree of their cognitive impairment.
Furthermore, measures of functional ability show
adequate psychometric properties (i.e. discriminant
power) to contribute to the MCI diagnosis.
Functional measures based on quantitative rates of
number and quality of ADL performed seem to be
more sensitive to identifying functional impairment
in MCI than those based on a subjective judgment
of disability.
The idea of a functional compromise associated
with MCI is not new, and previous studies have
reported a higher degree of functional impairment in
MCI subjects when compared with matched healthy
subjects (Tam et al., 2007; Pereira et al., 2008;
Ahn et al., 2009; Burton et al., 2009; Schmitter-
Edgecombe et al., 2009; Aretouli and Brandt,
2010; Bangen et al., 2010; Reppermund et al.,
2010; Teng et al., 2010a; 2010b). Independent
of the instrument used to evaluate functional
ability, most of these studies agree that higher
order ADL are more likely to be impaired than
those ADL with a lower degree of cognitive
involvement/demand (Burton et al., 2009; Aretouli
and Brandt, 2010; Reppermund et al., 2010). In
our results, the highest effect sizes between healthy
controls and MCI subjects were functioning areas
related to cognitive difficulties (CHART cognitive
subscale; WHO-DAS II communication subscale),
and participation in productive and social activities
(CHART occupation and mobility subscales;
WHO-DAS II life activities and participation
subscales). All these data support the apriori
intuitive notion that highly cognitive-dependent
living skills are more likely to be affected as a
consequence of cognitive impairment, and that
MCI subjects show significant impairment in these
functional domains. On the other hand, it is
noteworthy that differences between healthy and
MCI subjects were not restricted to higher order
ADL, but also to functional areas such as moving
around and self-care, usually referred to as basic
The early descriptions of MCI excluded the
presence of disability or functional impairment
as a characteristic, perhaps to differentiate from
dementia. However, as a consequence of the
enrichment and improvement of the conceptual
definitions of functional independence and parti-
cipation, and the increasing importance of these
concepts in the sphere of health and well-being (see
WHO International Classification of Functioning,
Disability and Health: WHO-ICF), instruments to
assess independent living abilities have improved
their ability to identify impairments included in
WHO-ICF activity and participation levels. In
WHO-ICF, the concept of disability is no longer
restricted to the notion of “inability to perform
basic ADL,” but includes quantitative (inability,
reduction in the number of times the ADL
is performed) or qualitative (increased time or
difficulty in performing ADL) difficulties with both
basic and instrumental ADL (see Wade, 2005 for an
interesting approach to the application of the WHO-
ICF model to patients with cognitive deficits). As
a result of this paradigm shift, and in the light of
1502 I. Bombin et al.
previous and the present results, it would be very
helpful for clinicians, caregivers, and health-system
managers if MCI definitions included the presence
of impairment of functional abilities as a clinical
feature inherent to MCI.
Moreover, given the moderately good psy-
chometric properties demonstrated in our study
of the CHART in discriminating healthy from
MCI subjects, assessing functional ability would
improve the identification of MCI subjects, and the
use of qualitative and/or quantitative impairment
of functional abilities as an MCI diagnostic
criterion should be further explored. Goldberg
et al. (2010) found that a sensitive performance-
based measure they developed (the University of
California, San Diego Performance-Based Skills
Assessment; UPSA) had a remarkably good
discriminant power to distinguish healthy from
MCI (area under the curve 0.84), and to
distinguish MCI subjects from Alzheimer’s disease
patients (area under the curve 0.88). Hence, the
inclusion of functional competence measures seems
convenient for the screening and early identification
of neurodegenerative processes characterized by
cognitive impairment.
As to the type of functional assessment
instrument, our results suggest that performance-
rate measures of functioning are superior to those
based on a subjective judgment of disability.
The latter was consistently more biased by
depressive symptoms, and the CHART showed
better discriminant power between healthy and
MCI groups than the WHO-DAS II, suggesting
that the more objective the approach to measuring
independent functioning, the more sensitive it
was to to functioning loss secondary to cognitive
impairment. In this regard, the study by Pereira
et al. (2008) also reported high effect sizes
between healthy subjects, MCI subjects, and
Alzheimer’s disease patients with an objective
measure of functioning; the Direct Assessment
of Functional Status Scale (DAFS-R) (Loewen-
stein et al., 1989), which evaluates functional
competence by simulating ADL (time orientation,
communication skills, ability to deal with finances,
shopping, grooming, eating, and transportation).
Additionally, the associations found between the
DAFS-R and cognitive measures of executive
functions were quite robust (r=−0.872, p<
0.001). The previously noted study of Goldberg
et al. (2010) showed that their performance-based
measure of functional ability was more discriminant
of healthy-MCI- Alzheimer’s disease groups than a
questionnaire based on a caregiver response. Hence,
independent functioning assessment instruments
should be designed in a way that places emphasis
on the subject’s ability to perform complex ADL
and the frequency with which such activities are
performed, rather than on subjective judgments of
Our results also noted that subjective judgments
of disability (i.e. WHO-DAS II) are more influenced
by depressive symptoms, suggesting depression
may play a confounding role in this measure.
That the most robust predictor of the WHO-
DAS II score was the severity of depressive
symptoms, and that the amount of variance
explained was close to 20% support this
hypothesis. By contrast, the more objective measure
of functional ability was less influenced by
depression, although it is noteworthy that in md-
MCI subjects, depression symptoms influenced
functional impairment as measured by both WHO-
DAS II and CHART, and that this group showed
higher rates of depressive symptoms than the other
two (healthy and a-MCI groups). Hence, it may
be the case that when depressive symptoms reach
syndromic levels, they play a more important
role in independent functioning. The alternative
hypothesis would be that depressive symptoms
are partially secondary to functional impairment.
The relationship between depression and functional
impairment in MCI subjects requires further
examination, because our study design does not
allow us to disentangle the relationship between
depression and functional impairment. On the other
hand, the influence of depression on functioning
measures may have been partially increased in
those cases in which these scales were administered
to subjects without an independent informant to
contrast information.
We found several results supporting the associ-
ation of the degrees of functional impairment with
cognitive impairment. The evidence supporting this
association is the finding that the higher the number
of impaired cognitive domains the higher the degree
of functional impairment, so that healthy controls
showed more functional independence than a-
MCI, and these more than md-MCI. A similar
gradual profile of global cognitive functioning can
be found between the three groups. The ability of
cognitive functioning to predict performance rates
of functional activities (CHART) was restricted to
MCI subjects also supports this notion, suggesting
that the impact of cognition on functional ability
gets higher as cognitive impairment increases. In
other words, variability on cognitive functioning
is irrelevant when cognitive functioning is within
normal limits, but when cognitive resources are
impaired they show a higher weight on functional
independence. The higher contribution of cognitive
measures on the regression model of all subjects
together (around 11.6%) is putatively due to
the heterogeneity of the entire sample, whereas
Functional impairment as MCI defining feature 1503
no cognitive measure seems to predict functional
ability in a-MCI subjects because these subjects
have a very similar cognitive profile (i.e. all subjects
present memory impairment alone). In other words,
the stratification based on their degree of cognitive
impairment is likely to be the best predictor of
functional impairment.
Limitations of the study include the potential
measure error derived from the fact that in
many cases the MCI subjects were the informants
of their own functional independence levels.
Although functional assessment was conducted in
an interview context with the collaboration of a
caregiver when available, for approximately half
the sample the subject was the key informant
and the accuracy of the subjects’ reports might
have been mediated by their cognitive impairment
and/or depression symptoms. However, given that
recruitment was mostly conducted in community
locations, a close informant was not always
available with enough knowledge of the subject’s
daily routine. Unfortunately, the exact number of
measures gathered from subjects only versus those
gathered from subjects and caregivers together was
not recorded. A second methodological issue is that
the sample recruitment may have been biased as
invitation to participate in the study was addressed
to people willing to participate in a memory training
program, and hence it could be argued that people
with subjective memory complaints were more
likely to enroll in the study. As a consequence,
our healthy subjects might have presented more
subjective memory complaints than the general
population. However, given the large sample size,
the effect size differences between healthy and
MCI groups on the subjective memory complaints
scale (MFE), and that most participants (including
all healthy subjects) were recruited in community
settings, we consider the sample to be representative
of the elderly living in the community. Finally,
cognitive and functional assessments were in most
cases performed by the same person, and although
group assignment (healthy vs. a-MCI vs. md-MCI)
was not undertaken until the conclusion of all data
gathering, this may have led to possible bias in
functional ability assessment.
In summary, these and previous results
emphasize the presence of qualitative and
quantitative functional impairments of both basic
and instrumental ADL in MCI as a logical
consequence of cognitive impairment. Although
dementia is characterized by a more severe
degree of disability than MCI, the WHO-ICF
conceptualization of disability would include MCI
as a disabling condition, although to a lower degree.
The need for a better definition of disability as
a diagnostic criterion (putatively, by shifting from
a categorical notion of able/disable to a more
spectrum/gradual approach) to discriminate MCI
from dementia must not conceal the fact that
MCI subjects have their own health/functional
assistance needs. Researchers and clinicians have
the responsibility and opportunity of designing,
testing, and implementing effective therapeutic
strategies targeted to improve, or at least preserve,
both functional and cognitive functioning in MCI.
Conflict of interest
Description of authors’ roles
I. Bombin designed the study, supervised the data
collection, and wrote the paper. S. Santiago-Ramajo
collected the data and assisted with writing the
paper. M. Garolera, E. M. Vega-González, N.
Cerulla, A. Caracuel, A. Cifuentes, and M. T.
Bascarán collected the data and assisted with
preparation of data for analyses. J. Bobes assisted
with design of the study. All authors reviewed the
paper and contributed to its final version.
This study was financially supported by the Spanish
Ministry of Science and Innovation, Instituto
de Salud Carlos III, and European Regional
Development Fund (ERDF).
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... To our knowledge, only one study examined the interplay between negative mood, physical health, and EFs in patients with MCI. It documented that objectively assessed functional independence of individuals exhibiting amnestic multidomain MCI was predicted by age, a composite index of attention (which also included some measures of inhibition), and self-reported depressive signs (Bombin et al., 2012). Despite this relevant evidence, further research is needed to clarify the nature of the associations between the different dimensions of psychological well-being, EFs, and HGS of cognitively impaired older individuals. ...
... Based on previous literature: 1) significant negative associations between HGS and depressive symptoms were expected (Ashdown-Franks et al., 2019;Taekema et al., 2010), as well as a positive association between the former and psychological well-being was hypothesized (Metz, 2000); 2) significant relationships between EFs and HGS were also hypothesized (Camargo et al., 2016;McGough et al., 2013;Tseng et al., 2013); 3) better EFs were expected to be associated with better coping strategy (Nieto et al., 2020); 4) EFs were expected to be a significant predictor of HGS (Hesseberg et al., 2020;Mose, 2016) and life satisfaction (Toh et al., 2020), respectively; 5) motor deficits were expected to predict depressive symptoms (Veronese et al., 2017); 6) more cognitively impaired participants were expected to exhibit less motor efficiency and fewer coping strategies than older participants with MCI (Bombin et al., 2012;Siltanen et al., 2019); and 7) individuals with MCI were expected to show better perceived psychological well-being than demented peers (Carmel et al., 2017). Due to the lack of relevant evidence, a priori further hypotheses were not stated. ...
... Thus, it can be concluded that even when cognitive decline occurs, the efficiency of control processes is essential to maintain hand muscular strength, and that the maintenance of both motor and higher-order cognitive resources is necessary to handle everyday problems, and therefore, to maintain adequate levels of perceived psychological well-being. Additionally, extending previous studies (Bombin et al., 2012;Carmel et al., 2017;Siltanen et al., 2019), when HGS was used as a covariate, participants displaying less cognitive impairment also self-reported better total psychological well-being, coping, and higher emotional competence. Compared to the national norms for healthy older people provided by De Beni et al. (2007), our participants with the most severe cognitive decline had very low levels of coping, emotional competence, and total well-being, whereas the participants with MCI reported medium levels in the aforementioned measures. ...
Full-text available
The contribution of motor efficiency to the maintenance of psychological well-being in cognitively impaired older individuals is still insufficiently examined. This investigation primarily intended to evaluate whether muscular strength mediates the relationship between different facets of psychological well-being (i.e., personal satisfaction, emotional competence, coping), negative mood, and central executive efficiency through the Clock-Drawing, Trail-Making (Part A), and verbal fluency tests. Furthermore, the impact of cognitive decline on self-reported psychological well-being and depression was explored, using the handgrip strength (HGS) measure as a covariate. One hundred and nineteen older participants, 44 males and 75 females, aged 63 years and older (M age = 77.7 years, SD = 5.6 years), completed a battery of tests assessing executive functions, HGS, depression, and psychological well-being. Significant low to moderate associations were found between distinct executive functions, HGS, psychological well-being, and depression. In addition, personal satisfaction did not correlate with any measure of executive functions, the clock-drawing score was associated only with coping index, and self-reported depression correlated only with the Trail-Making Test score. Moreover, a series of mediation analyses documented that executive functions (primarily assessing verbal fluency and motor speed) and HGS explained approximately 20-46% of the variance in perceived psychological well-being and depression. Finally, more cognitively impaired participants reported worse total psychological well-being, emotional competence, and coping. In conclusion, motor proficiency mediates the relationship between selective measures of executive functions and perceived psychological well-being and depression in cognitively impaired individuals.
... Numerous studies have confirmed that cognitive impairments persisted throughout the degeneration process from aMCI to AD (Dunn et al., 2014;Lehrner et al., 2005;Liu et al., 2019b;Serra et al., 2010). Our study findings are in consistence with previous studies (Bombin et al., 2012;Liao et al., 2017) which also demonstrated that aMCI patients had cognitive impairment across five cognitive domains, including executive function, language, memory, processing speed, and visuospatial ability, similar to RGD patients. In addition, we found that the RGD-aMCI group showed more severe impairments in both executive function and memory compared to RGD and aMCI groups. ...
Objectives: Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer's disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD. Design: Cross-sectional study. Participants: A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited. Measurements: All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted. Results: In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups. Conclusions: The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.
... The presence of functional impairment was excluded in early definitions of MCI, but some recent studies have reported varying degrees of functional impairment associated with MCI (Farias et al., 2006). Furthermore, functional impairment is a defining feature of MCI and is partially dependent on the degree of cognitive impairment, and functional ability seems to be more related to depression (Bombin et al., 2012). Executive functions are independently related to anxiety disorders in MCI patients (Rozzini et al., 2009). ...
Full-text available
Objective: Mild cognitive impairment (MCI) is an important risk state for dementia, particularly Alzheimer’s disease (AD). Depression, anxiety, and apathy are commonly observed neuropsychiatric features in MCI, which have been linked to cognitive and functional decline in daily activities, as well as disease progression. Accordingly, the study’s objective is to review the prevalence, neuropsychological characteristics, and conversion rates to dementia between MCI patients with and without depression, anxiety, and apathy. Methods: A PubMed search and critical review were performed relating to studies of MCI, depression, anxiety, and apathy. Results: MCI patients have a high prevalence of depression/anxiety/apathy; furthermore, patients with MCI and concomitant depression/anxiety/apathy have more pronounced cognitive deficits and progress more often to dementia than MCI patients without depression/anxiety/apathy. Conclusions and Implications: Depression, anxiety, and apathy are common in MCI and represent possible risk factors for cognitive decline and progression to dementia. Further studies are needed to better understand the role and neurobiology of depression, anxiety, and apathy in MCI.
... This dependency is greater in severe and moderate cases. These results are in line with the findings of Bombin et al. [29] and De Vriendt et al. in Belgium [13]. ...
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Introduction: The escalating rate of old people with a functional impairment in Iran and the weakness of the family support due to the diminishing of family size have increased the demand for long-term care for the elderly with cognitive impairment (CI). Objective: The purpose of this research is to explore the frequency of cognitive impairment in the elderly and its association with their daily functional impairment and disability. Method: This is a cross-sectional and descriptive-analytic study conducted in 2016-2017. The study sample consisted of 393 elderly people who were 60 years old or older who live in of Guilan different counties. Samples were selected by using multi-stage cluster sampling. Subsequently, data were analyzed by using the Chi-square test and correlation and regression analysis conducted in SPSS 22. Results: It was observed that 4.3, 28.6, and 37% of the subjects suffered from severe, moderate, and mild cognitive impairment, respectively. Cognitive impairment had a significant relationship with daily functioning and activities requiring special tools. Moreover, cognitive impairment in women, people with low education, and those over 70 years old was more common, and the difference between them was significant (p <0.001). Also, disability was significantly greater in the elderly with cognitive impairment. Conclusion: Many old people need to be cared for after the appearance of cognitive impairment. Therefore, appropriate screening of cognitive impairments is conducive to early diagnosis and prevention of executive functioning problems.
... These findings build on previous work and suggest that executive dysfunction may impact more discrete upper extremity components of these tasks such as reaching for and grasping objects central to task completion. It follows that frontally-mediated cognitive processes (e.g., processing speed, selective attention, self-monitoring) are required for the execution and/or coordination of seemingly basic motor components of daily tasks, which is further supported by research revealing relations between cognition and motor abilities (12)(13)(14)(15)(16). Further, that the mdMCI group specifically demonstrated poorer self-reported upper extremity activities than no-MCI participants is consistent with research showing that the combination of executive and memory impairment in MCI is associated with more severe functional activity limitation than single-domain MCI (44,45). ...
Background Individuals with mild cognitive impairment (MCI), often a precursor to dementia, experience limitations in completing daily activities. These limitations are particularly important to understand, as they predict risk for dementia. Relations between functional changes and both cognitive decline and upper extremity motor impairments have been reported, but the contribution of motor function to relations between cognitive function and functional independence remains poorly understood. We examined the relationship between cognition and upper extremity activities, and if this relation was mediated by motor function. Methods 430 community-dwelling primary care patients ages ≥ 65 from the Boston Rehabilitative Impairment Study of the Elderly (RISE) completed self-report measures of upper extremity function, tests of neuromuscular attributes to measure motor function (reaction time, pronosupination of the hands), and neuropsychological measures. Participants were classified based on cognitive performance into groups: MCI and without MCI; with MCI further classified by cognitive subtype. Regression and mediation analyses examined group differences and relations between cognitive function, upper extremity function, and neuromuscular attributes. Results MCI participants demonstrated poorer neuromuscular attributes and self-reported upper extremity function, and neuromuscular attributes significantly mediated positive relations between cognitive status and self-reported upper extremity function. Poorer self-reported upper extremity function was most prominent for groups with executive dysfunction. Conclusions Together with previous research, results suggest that the relationship between cognitive function, motor function, and functional activities are not confined to mobility tasks but are universally related to body systems and functional activities. These findings inform new approaches for dementia risk screening and rehabilitative care.
... The presence of a major depression was ruled out prior to the diagnosis in MCI and AD. However, mild to moderate depressive symptoms are an important comorbidity of cognitive disorders and may have an impact on everyday activities [99][100][101][102]. ...
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Background Assessment of activities of daily living (ADL) is paramount to determine impairment in everyday functioning and to ensure accurate early diagnosis of neurocognitive disorders. Unfortunately, most common ADL tools are limited in their use in a diagnostic process. This study developed a new evaluation by adopting the items of the Katz Index (basic [b-] ADL) and Lawton Scale (instrumental [i-] ADL), defining them with the terminology of the International Classification of Human Functioning, Disability and Health (ICF), adding the scoring system of the ICF, and adding the possibility to identify underlying causes of limitations in ADL. Methods and findings The construct validity, interrater reliability, and discriminative validity of this new evaluation were determined. From 2015 until 2016, older persons (65–93 y) with normal cognitive ageing (healthy comparison [HC]) (n = 79), mild cognitive impairment (MCI) (n = 73), and Alzheimer disease (AD) (n = 71) underwent a diagnostic procedure for neurocognitive disorders at the geriatric day hospital of the Universitair Ziekenhuis Brussel (Brussels, Belgium). Additionally, the ICF-based evaluation for b- and i-ADL was carried out. A global disability index (DI), a cognitive DI (CDI), and a physical DI (PDI) were calculated. The i-ADL-CDI showed high accuracy and higher discriminative power than the Lawton Scale in differentiating HC and MCI (area under the curve [AUC] = 0.895, 95% CI .840–.950, p = .002), MCI and AD (AUC = 0.805, 95% CI .805–.734, p = .010), and HC and AD (AUC = 0.990, 95% CI .978–1.000, p < .001). The b-ADL-DI showed significantly better discriminative accuracy than the Katz Index in differentiating HC and AD (AUC = 0.828, 95% CI .759–.897, p = .039). This study was conducted in a clinically relevant sample. However, heterogeneity between HC, MCI, and AD and the use of different methods of reporting ADL might limit this study. Conclusions This evaluation of b- and i-ADL can contribute to the diagnostic differentiation between cognitively healthy ageing and neurocognitive disorders in older age. This evaluation provides more clarity and nuance in assessing everyday functioning by using an ICF-based terminology and scoring system. Also, the possibility to take underlying causes of limitations into account seems to be valuable since it is crucial to determine the extent to which cognitive decline is responsible for functional impairment in diagnosing neurocognitive disorders. Though further prospective validation is still required, the i-ADL-CDI might be useful in clinical practice since it identifies impairment in i-ADL exclusively because of cognitive limitations.
Individuals with mild cognitive impairment (MCI) can often progress into Alzheimer’s Disease (AD). Research suggests that decline in episodic memory and semantic memory, as well as functional abilities, can be sensitive in predicting disease progression. This study aimed to (a) investigate episodic and semantic memory performance differences between AD and MCI, (b) determine if memory performance predicts observation-based activities of daily living (ADLs), and (c) explore whether semantic memory mediates the relationship between episodic memory and ADLs. Fifty-eight AD, 53 MCI, and 72 healthy control participants were administered the Rey-O, California Verbal Learning Test, Animal Fluency Test, Boston Naming Test, and Direct Assessment of Functional Status (DAFS). The results revealed, first, that AD participants performed significantly lower than the MCI participants across semantic memory and episodic memory tasks, with the exception of the Boston Naming Test. Second, hierarchical-stepwise regression analyses found that semantic memory significantly predicted DAFS orientation, communication, and financial skills in AD, but episodic memory predicted shopping skills. Furthermore, semantic memory significantly predicted DAFS transportation skills in AD and MCI. Third, within the overall sample, semantic memory mediated the relationship between episodic memory and ADLs. Taken together, the findings suggest decline in semantic memory (as measured by confrontational naming and category fluency) and episodic memory (as measured by list and complex visual design learning and recall) may lead to decline in different and specific aspects of functional abilities in AD and MCI.
Background: Ageing is associated with increased morbidity, depression and decline in function. These may consequently impair the quality of life (QoL) of older adults. Purpose: This study was used to investigate the prevalence of functional disability, depression, and level of quality of life of older adults residing in Uyo metropolis and its environs, Nigeria. Method: This cross sectional survey involved 206 (116 females and 90 males) older adults with mean age of 69.8±6.7. The World Health Organization Quality of Life-OLD, Functional status Questionnaire (FSQ) and Geriatric Depression Scale (GDS) were used to measure quality of life, functional disability and depression respectively. Data was analysed using frequency counts and percentages and Spearman rank-order correlation coefficient, at 0.05 alpha level. Results: 45.5% of participants had depression, and at least 30% had functional disability in at least one domain, but their quality of life was fairly good (>60.0%) across all domains. Significant correlation existed between depression scores and individual quality of life and functional disability domains and between overall QoL and each functional disability domain (p<0.001). Conclusions: Depression and functional disability were quite prevalent among sampled older adults but their QOL was not too severely affected. Since the constructs were interrelated, it seems interventions targeted at depression and functional status may invariably enhance the quality of life of the older adults.
Remitted late life depression exhibits persistent cognitive impairments and enhances the risk of dementia. This study aimed to examine the characteristics of cognitive dysfunction in remitted late life depression and amnestic mild cognitive impairment (MCI). Remitted late life depression (n=61), amnestic MCI (n=61) and age-education-matched controls (n=65) were evaluated with a battery of neuropsychological tests grouped into executive function, memory, processing speed, attention and visuospatial domains. Compared with control subjects, amnestic MCI individuals showed more severe cognitive impairments in all domains, while remitted late life depression individuals performed worse in executive function and memory. The pattern of cognitive profiles significantly differed between remitted late life depression and amnestic MCI groups, which might be mainly attributed to worse impairments in memory and executive function in amnestic MCI individuals. Executive function was the core impaired cognitive domain mediating the influence of predictors on other cognitions in both remitted late life depression and amnestic MCI groups, which indicated a possible etiopathogenic mechanism underlying the conversion to dementia.
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Purpose: This systematic review examines research and practical applications of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) as a basis for establishing specific criteria for evaluating relevant international scientific literature. The aims were to establish the extent of international dissemination and use of WHODAS 2.0 and analyze psychometric research on its various translations and adaptations. In particular, we wanted to highlight which psychometric features have been investigated, focusing on the factor structure, reliability, and validity of this instrument. Method: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology, we conducted a search for publications focused on “whodas” using the ProQuest, PubMed, and Google Scholar electronic databases. Results: We identified 810 studies from 94 countries published between 1999 and 2015. WHODAS 2.0 has been translated into 47 languages and dialects and used in 27 areas of research (40% in psychiatry). Conclusions: The growing number of studies indicates increasing interest in the WHODAS 2.0 for assessing individual functioning and disability in different settings and individual health conditions. The WHODAS 2.0 shows strong correlations with several other measures of activity limitations; probably due to the fact that it shares the same disability latent variable with them. Implications for Rehabilitation WHODAS 2.0 seems to be a valid, reliable self-report instrument for the assessment of disability. The increasing interest in use of the WHODAS 2.0 extends to rehabilitation and life sciences rather than being limited to psychiatry. WHODAS 2.0 is suitable for assessing health status and disability in a variety of settings and populations. A critical issue for rehabilitation is that a single “minimal clinically important .difference” score for the WHODAS 2.0 has not yet been established.
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This is a book, not a paper.
This chapter advocates the use of the World Health Organization's International Classification of Functioning (WHO ICF) model when thinking about cognitive rehabilitation, and shows how research into effectiveness needs to consider careful study of both individual patients and group studies. The WHO ICF model is a descriptive system that can be transformed into a powerful way of analysing illness. In relation to cognitive deficits, it highlights the fact that cognitive impairments are conceptual constructs that are derived from behavioural observations, and that the associated disability or disabilities are not in themselves specifically attributable to a single 'cognitive' deficit. It also highlights that rehabilitation for patients with cognitive losses may well involve many different interventions at many different levels, not simply attempting to reverse the loss itself. Models of illness are important. They facilitate a systematic and logical analysis of clinical problems and hopefully thereby allow for a more coherent plan of treatment to be devised and implemented. The World Health Organization's International Classification of Functioning (WHO ICF) is a descriptive system that can be transformed into a powerful way of analysing illness. In relation to cognitive deficits, it highlights the fact that cognitive impairments are conceptual constructs that are derived from behavioural observations, and that the associated disability or disabilities are not in themselves specifically attributable to a single 'cognitive' deficit. It also highlights that rehabilitation for patients with cognitive losses may well involve many different interventions at many different levels, not simply attempting to reverse the loss itself.
Instrumental activities of daily living (IADL) are complex activities necessary for independent living, such as handling finances, managing medication or using domestic appliances. The loss to perform IADL independently is a major factor affecting the quality of life in patients with dementia. The diagnostic criteria for mild cognitive impairment (MCI) allow for minimal impairment in complex IADL (Petersen et al., 2004, Winblad et al., 2004), however, neither is minimal impairment defined nor are clinicians and research studies using the same instruments to assess IADL. It has been shown that IADL can be impaired before a diagnosis of dementia is warranted. The presence of MCI combined with impaired IADL is associated with a higher conversion rate to dementia, a shorter time to clinically manifest a diagnosis of dementia and a lower chance to reverse to normal (Luck et al., 2010). These findings also indicate that individuals with MCI require help with complex IADL and can result in financial and psychological burden for family members. Some IADL are more cognitively demanding than others and recent findings suggest that restrictions in functional abilities in individuals with MCI are in particular present in high cognitively demanding activities (Reppermund et al., 2011). These high cognitively demanding IADL are associated with cognitive performance in several domains and men seem to have more difficulties than women to perform IADL with a higher demand on cognitive capacities. Future research into IADL in MCI should focus on the distinction between physical disabilities and low IADL performance and on how assistance can be provided for individuals who do not suffer from dementia but whose cognitive and functional performance is not normal either.
Background Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials.Objective To characterize clinically subjects with MCI cross-sectionally and longitudinally.Design A prospective, longitudinal inception cohort.Setting General community clinic.Participants A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn.Main Outcome Measures The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale–Revised, Wechsler Memory Scale–Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, respectively.Results The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD.Conclusions Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
Many patients with brain damage are left with a range of neuropsychological deficits that impair normal cognitive process. It is generally recognised that these less obvious cognitive deficits (including memory, language, perception, attention and executive disorders) militate against full recovery often to a greater extent than more traditional medical deficits (e.g. paralysis, sensory loss, etc). Recognition of this has helped fuel the exponential growth in cognitive neuropsychology and neuroscience over the past 30 years. In turn, this theoretical approach has been used to guide and inform the development of cognitive therapies designed to remediate cognitive impairments and their functional consequences. Cognitive rehabilitation has over the last decade grown to become an established and influential therapeutic approach. There is now a considerable body of knowledge describing the principles and theoretical basis for analysing and directing treatments to selective cognitive deficits. Despite this, the clinical effectiveness and extent to which cognitive theory can inform therapeutic treatment has been questioned. It is timely, therefore, to evaluate and discuss the type and quality of evidence used in support of cognitive rehabilitation. In this book, some of the most influential clinicians and cognitive neuroscientists in the world critically review and discuss the effectiveness of rehabilitation methods currently used to treat patients with cognitive impairments following acquired brain damage. It provides a much needed critique and consensus about what should constitute best practice. The book will be valuable for all those who have to deal with the neuropsychological and neurological effects of brain damage, including, neuropsychologists, neuropsychiatrists, neurologists, experimental pscyhologists, and neuroscientists.
While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between individuals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions. The sample of 762 community-living participants aged 70-90 were assessed with a comprehensive neuropsychological test battery and with the informant-completed Bayer-Activities of Daily Living Scale (B-ADL). Compared to cognitively normal individuals, the MCI group was rated as having more difficulties on the B-ADL and performed worse on cognitive tests. Factor analysis of the B-ADL items yielded two factors, which were labelled 'high cognitive demand' (HCD) and 'low cognitive demand' (LCD). Individuals with MCI scored worse than cognitively normal participants on the HCD factor but similarly on the LCD factor. Men were rated as having more difficulties on the HCD, but not the LCD, factor compared to women. The HCD factor score correlated significantly with all five cognitive domains measured, but the LCD factor correlated significantly only with attention/processing speed and to a lesser extent with executive function. Having more difficulties in IADL, especially those with higher demand on cognitive capacities, was found to be associated with MCI and overall cognitive functioning. This has implications for the definition of MCI, as lack of functional impairment is generally used as a criterion for diagnosis.
We investigated the prevalence of mild cognitive impairment (MCI) in Olmsted County, MN, using in-person evaluations and published criteria. We evaluated an age- and sex-stratified random sample of Olmsted County residents who were 70-89 years old on October 1, 2004, using the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychological testing to assess 4 cognitive domains: memory, executive function, language, and visuospatial skills. Information for each participant was reviewed by an adjudication panel and a diagnosis of normal cognition, MCI, or dementia was made using published criteria. Among 1,969 subjects without dementia, 329 subjects had MCI, with a prevalence of 16.0% (95% confidence interval [CI] 14.4-17.5) for any MCI, 11.1% (95% CI 9.8-12.3) for amnestic MCI, and 4.9% (95% CI 4.0-5.8) for nonamnestic MCI. The prevalence of MCI increased with age and was higher in men. The prevalence odds ratio (OR) in men was 1.54 (95% CI 1.21-1.96; adjusted for age, education, and nonparticipation). The prevalence was also higher in subjects who never married and in subjects with an APOE epsilon3epsilon4 or epsilon4epsilon4 genotype. MCI prevalence decreased with increasing number of years of education (p for linear trend <0.0001). Our study suggests that approximately 16% of elderly subjects free of dementia are affected by MCI, and amnestic MCI is the most common type. The higher prevalence of MCI in men may suggest that women transition from normal cognition directly to dementia at a later age but more abruptly.
Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices. We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ). IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function. IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk.
Current criteria for mild cognitive impairment (MCI) require "essentially intact" performance of activities of daily living (ADLs), which has proven difficult to operationalize. We sought to determine how well the Functional Activities Questionnaire (FAQ), a standardized assessment of instrumental ADLs, delineates the clinical distinction between MCI and very mild Alzheimer disease (AD). We identified 1801 individuals in the National Alzheimer's Coordinating Center Uniform Data Set with MCI (n=1108) or very mild AD (n=693) assessed with the FAQ and randomized them to the development or test sets. Receiver-operator curve (ROC) analysis of the development set identified optimal cut-points that maximized the sensitivity and specificity of FAQ measures for differentiating AD from MCI and were validated with the test set. ROC analysis of total FAQ scores in the development set produced an area under the curve of 0.903 and an optimal cut-point of 5/6, which yielded 80.3% sensitivity, 87.0% specificity, and 84.7% classification accuracy in the test set. Bill paying, tracking current events, and transportation (P's<0.005) were the FAQ items of greatest diagnostic utility. These data suggest that the FAQ exhibits adequate sensitivity and specificity when used as a standardized assessment of instrumental ADLs in the diagnosis of AD versus MCI.