Mental Fatigability and MCI……
1
Mental Fatigability and MCI
2
Reliability, validity and prevalence of an index of cognitive symptoms
3
A Starmark1, M.Sc.; P Hellström1, M.Sc.; M Rödholm1*, M.D. Ph.D.; E Svensson2; Ph.D., U
4
Norrsell1, M.D. Ph.D.; J-E Starmark1, M.D., Ph.D; L Rönnbäck, MD., PhD1.
5
1
6
bilitation, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; 2 Depart-
7
ment of Statistics (ESI), Örebro University, Örebro, Sweden. *present address: Adult Psychi-
8
atric Clinic 2, Södra Älvsborg Hospital, Borås, Sweden.
9
Corresponding author: Anders Starmark, Institute of Neuroscience and Physiology, Depart-
10
ment of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at Göteborg
11
University, Blå Stråket 7, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden. E-
12
mail: Anders_Starmark@yahoo.se
1
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Reha-
13
ACKNOWLEDGEMENTS: The authors are grateful to Peter F Berglund M.D., Ph.D. for
14
valuable comments. The work was supported by the Swedish Parkinson Foundation,
15
Göteborg’s Parkinson Foundation, Hjalmar Svensson’s Foundation, Rune and Ulla Almlöf’s
16
Foundation, Edith Jacobsson’s Foundation and the Sahlgrenska Academy at Göteborg Uni-
17
versity.
18
Full Title: Mental Fatigability and MCI. Reliability, validity and prevalence of an index of
19
cognitive symptoms.
20
Cover Title: Mental Fatigability and MCI.
21
Tables: 2
Mental Fatigability and MCI……
1
Figures: 5 black-and-white drawings
2
Key Words: Cognitive disorders; disability evaluation; Trail Making Test; MCI; inter-
3
observer agreement
4
Word Count: 5731 words
5
2
Mental Fatigability and MCI……
1
ABSTRACT
2
CONTEXT: Mental fatigability, impaired concentration and memory disturbances are common
3
symptoms among patients after aneurysmal subarachnoid hemorrhage (aSAH).
3
4
5
OBJECTIVES: To develop an index of mental fatigability, concentration and/or memory
6
difficulties (FCM) and to study the reliability, validity and the point prevalence rates of FCM
7
in psychiatric disorders at 12 months after a aSAH.
8
9
DESIGN: An exploratory cross-sectional study of a new index using CPRS items. Reliability
10
was recalculated from an earlier published series. Validity was estimated as agreement with
11
social function (Glasgow Outcome Scale; GOS) including a set of complex ADL activities.
12
Five groups of patients were analyzed: “recovered”, FCM only, depressive/anxiety disorders,
13
Personality Change from a General Medical Condition (PCGMC) and dementia. The validity
14
of diagnostic groups was checked with a developed extension of the MMSE and Trail Making
15
Test (E-TMT).
16
17
SETTING: University Hospital, outpatient clinic.
18
19
PATIENTS: Eighty consecutive patients after aSAH from two cohorts were pooled for the
20
validity study. Median age was 55 years (quartiles 48 to 62).
21
22
MAIN OUTCOME MEASURES: Spearman Rho, Monotonic Agreement (MA), Pass/fail
23
scoring (E-TMT). Fatigability effect. Prevalence rates.
24
Mental Fatigability and MCI……
4
1
RESULTS: Inter-correlations between symptoms varied between 0.39 (FM), 0.44 (CM) and
2
0.69 (FC) (p<0.001). The inter-observer agreement of FCM was 0.99 and the MA between the
3
new index and GOS was 0.92. MA for FCM versus MMSE score was 0. 56. The prevalence
4
rates of FCM was 77% overall, 96 % in depressive anxiety/disorders (n=24) and 85 % in
5
PCGMC (n= 20). The E-TMT successfully classified 58 % patients with FCM only, and
6
showed a good discrimination of PCGMC. No effect of mental fatigability was observed.
7
8
CONCLUSION: FCM can be assessed with a high inter-observer agreement, agrees well with
9
social impairment and is frequent in common psychiatric disorders after aSAH. Mental
10
11
fatigability should be considered for inclusion in MCI criteria.
Mental Fatigability and MCI……
1
5
Introduction
2
3
Aneurysmal subarachnoid haemorrhage (aSAH) is a subgroup of stroke disorders, mainly
4
affecting individuals 40-60 years old. It may result in a global brain disorder, which is asso-
5
ciated with psychiatric disorders and neuropsychological deficits.
6
7
Most neuropsychological studies on outcome after aSAH agree that the patients are particu-
8
larly impaired in functions of memory, attention, concentration and cognitive speed and flexi-
9
bility (Ljunggren 1985, Hütter 1995, Hellawell 1999). The most common symptoms
10
reported are concentration difficulties (21 % to 71%), memory dysfunction (37% to 57%) and
11
fatigue (47 % to 68 %). If these symptoms were to appear in a patient, the most suitable
12
DSM-IV diagnosis would be Mild Neurocognitive Disorder (MNCD). However, mental
13
fatigue is not part of the MNCD criteria (APA 1994, Gauthier 2006).
14
15
There are few studies done on MNCD, and Petersen (ref 2006) has suggested that Mild
16
Cognitive Impairment (MCI) should be included in DSM V. Most studies on MCI emphasize
17
the need for an objective measure for reported cognitive symptoms. “In order to determine the
18
specific subtype of MCI, comprehensive cognitive testing is necessary, using
19
neuropsychological testing, although there are currently no generally accepted instruments
20
recommended” (Winblad et al 2004, emphasis added). Rödholm et al (coverage 2003)
21
reported that, after the exclusion of patients fulfilling criteria of major depression, anxiety
22
disorders and patients with neuropsychological deficits, many patients will not receive a
23
specific psychiatric diagnosis according to DSM IV (64 %) or ICD10 (33%).
24
Mental Fatigability and MCI……
6
1
Although mental fatigability is not part of the MCI definition (Winblad 2004), De Luca (De
2
Luca 2005) considers mental fatigue a cognitive symptom. Clinical experience suggests a
3
strong relation between mental fatigability and concentration difficulties (Rödholm 2001).
4
We here propose a global index for the most common cognitive difficulties after an aSAH.
5
The reported symptoms: mental Fatigability, Concentration difficulties, impaired Memory
6
(FCM) can be assessed with high inter-observer agreement (Rödholm 2001). FCM symptoms
7
are considered as equal indicators of a global index of cognitive dysfunction. The validity of
8
FCM index could be investigated by the strength of the association between the index and the
9
social function of the patient such as the SOFAS scale in DSM IV (APA 1994), Glasgow
10
Outcome Scale (van Gijn 1994) and impairment in complex activities of daily living
11
(Perneczky 2006). Since aSAH patients are younger than the patients included in typical MCI
12
studies, this means that the capacity for work will be an important factor when considering
13
complex activities of daily living. Such an index should also be validated with an objective
14
test (Winblad 2004).
15
16
Many aSAH patients perform normally on isolated neuropsychological tests in spite of being
17
unable to work or socially handicapped (Rödholm 2003) and often the neuropsychologist
18
remarks on a patient’s fatigue in the status. It is difficult to perform a full neuropsychological
19
test battery before and after a blinded clinical assessment in order to measure an eventual
20
mental fatigability effect. For that reason, we decided to develop a new version of an existing
21
test, the Trail Making Test (TMT) - a measure of attention (Reitan 2004, 12; Rabin 2005)
22
and executive dysfunction (Tranel 2000) - as a suitable candidate for a surrogate measure of
23
overall “brain dysfunction”. This test is one of the most commonly used neuropsychological
24
tests (Rabin 2005). It is constructed in a manner which makes it possible to increase the
25
cognitive demands without altering the basic characteristics of the test, and it is easy to use.
Mental Fatigability and MCI……
1
The relationships between cognitive impairments, i.e. a broad cognitive state that is not part
2
of normal aging and different psychiatric disorders, especially depressive disorders are
3
seldom investigated (Steffens 2006). The FCM triad is part of the operational criteria for
4
major depression, minor depression and generalized anxiety disorder (GAD) (APA 1994). If
5
reliable and valid, the FCM index could be used for investigation of the prevalence rates in
6
common psychiatric disorders. Few studies on aSAH has investigated the prevalence of
7
depressive symptoms. Carter et al 2000, reported that 36 % of patients showed depressive
8
symptoms at follow-up, while Morris et al (2004) reported that 40 % of their patients
9
experienced severe anxiety 16 months after aSAH and 20 % experienced moderate to severe
10
depressive symptoms.
11
12
AIMS: Our aim was to construct an index for FCM, investigate the inter-observer reliability,
13
its relation to global social outcome, evaluate how the FCM severity and fatigability rating
14
affects performance on the new tests, and to estimate the prevalence of FCM in major
15
depressive, minor depressive, anxiety disorders, MCI (post-hoc) and in Personality Change
16
due to a General Medical Condition (PCGMC) after an aSAH.
17
18
19
7
Mental Fatigability and MCI……
8
1
2
MATERIAL AND METHODS
3
Patients
4
STUDY A
5
Reliability study
6
Data from 36 consecutive patients (Table 1) suffering from aSAH in a previously published
7
study of inter-observer agreement (Rödholm 2001) were reanalyzed using the method de-
8
scribed for FCM below.
9
Methods
10
The methods for assessment of symptoms are identical to Study B.
11
Study B
12
Studies of validity and prevalence.
13
Patients
14
The patients (Table 1) were admitted to the Department of Neurosurgery, Sahlgrenska
15
University Hospital, due to aSAH. The catchment area was the western region of Sweden,
16
with approximately 1.6 million inhabitants. The patients belonged to two different cohorts.
17
The first cohort (n=64) consisted of patients admitted between June 1996 and June 1997.
18
Patients in the second cohort were admitted between April 1997 and December 2002. This
19
cohort (n=98) was part of an international study of aSAH treatment (Molyneux 2002).
20
Patients in the first cohort all underwent embolization, while patients in the second cohort
21
were randomized to embolization or clip surgery. Altogether 24 patients died within a year
22
after surgery, 13 patients were lost to follow-up and 15 patients were excluded due to severe
Mental Fatigability and MCI……
9
1
dementia or severe aphasia. Twenty-five patients participating in a pilot study on TMT B and
2
extended TMT version C were also excluded. This group did not differ from the included
3
patients in terms of age, sex, education or FCM levels (data not shown). Finally, for various
4
reasons, five patients did not perform the extended TMT. Included in this study were 80
5
consecutive patients who all performed the TMT battery (see below and Table 1).
6
Table 1
7
8
Neuropsychiatric interview
9
All patients were investigated in a standardized way and in an outpatient setting. The order of
10
assessment instruments are shown in Figure 1. The whole assessment procedure took about
11
two hours.
12
Figure 1
13
14
After a general overview of the purposes of the investigation and collection of demographic
15
data, the TMT battery, A, B (Reitan 2004) and the new extended versions C and D was
16
performed by the patients.
17
The global cognitive level was assessed by means of the Mini-Mental State Examination
18
(MMSE; Folstein 1975). For the assessment of the patients’ neurological deficits the NIH
19
Stroke Scale (Goldstein 1989) was used supplemented with the Boston Naming Test (Kaplan
20
1983).
21
The initial testing was followed by a structured clinical interview according to the DSM-III-R
22
(Spitzer 1992) (the data from this interview were later translated to DSM IV (APA 1994)
23
criteria). This included the evaluation of presence or absence of Organic Mental Syndromes
24
including a modified version of the Comprehensive Psychopathology Rating Scale (Åsberg
25
1978, Svanborg 1994, Rödholm 2003). Information from relatives was used together with
Mental Fatigability and MCI……
10
1
CPRS item 45 (observed lack of appropriate emotion), item 5 (reported inability to feel), item
2
43 (hostility), item 44 (labile emotional responses), item 31 (ideas of persecution) and item 48
3
(distractibility) (Åsberg 1978) to establish the diagnosis and sub grouping of PCGMC (APA
4
1994).
5
6
An assessment of global social function was made according to the Swedish eight-degree
7
version of the Glasgow Outcome Scale (GOS; Svensson 2002). The eight categories are
8
Good recovery-High, Good Recovery-Low, Moderate Disability-High, Moderate Disability-
9
Low, Severe Disability- High, Severe Disability-Low, Vegetative State and Dead. The
10
operational definitions are given in (Svensson 2002). The five main categories are identical to
11
the original version by Jennett and Bond (Jennett and Bond 1975). The main differences
12
within Severe Disability (SD) is the number of impairments of aspects of personal ADL,
13
within Moderate Disability (MD) the number of impairments of instrumental and complex
14
ADL activities, and reduction of work capacity and within Good Recovery (GR) is whether or
15
not new physical or mental symptoms are occurring with an otherwise socially re-integrated
16
patient. The performance on complex ADL activities were recorded separately as Yes or No
17
questions related to cleaning the house, shopping, traveling with public transport, cooking,
18
recreation and social interaction. This information was used for the final classification of GOS
19
levels.
20
21
The battery of TMT with parallel versions of C and D tests concluded the evaluation.
22
23
All patients were examined by the same psychiatrist 12 months after the aSAH.
24
25
Constructing the FCM index
Mental Fatigability and MCI……
11
1
CPRS items are operationalised as 7-point scales, with four well-defined categories labeled 0,
2
1, 2, and 3; and three intermediate categories labeled 0.5, 1.5, and 2.5. We constructed a con-
3
dition based index, the Fatigability-Concentration-Memory index (FCM Index), in which the
4
individual’s level of FCM was defined by pairing the two highest levels of dysfunction in the
5
assessments of CPRS Item 15 (mental fatigability), Item 16 (concentration difficulties) and
6
Item 17 (memory disturbances) (Åsberg 1978). According to our hypothesis, the two worst
7
reported symptoms represent the “weakest links” of the patient’s cognitive function, and since
8
all are considered equally debilitating it does not matter which two of them are worst in the
9
individual case. The scheme of possible combinations of pairs is shown in Figure 2 as well as
10
the criteria for the four ordered categories of FCM according to our proposed index. The
11
numbers are CPRS levels for the worst two of mental fatigability, concentration difficulties
12
and memory difficulties. Since the index is symmetrical around the diagonal, which of the
13
items is “item 1” and which is “item 2” is immaterial. An individual with assessed levels of
14
2.5 in mental fatigability, 2 in memory difficulties and 1.5 in concentration difficulties will
15
get the pair [2, 2.5]. The corresponding cell (marked with a †) indicates Severe dysfunction.
16
Another individual reported 0 in mental fatigability and concentration difficulties, and 2 in
17
memory difficulties. The patient has the pair [0, 2], representing Moderate dysfunction.
18
19
(Figure 2)
20
21
Assigning patients to groups
22
The focus was on those patients who reported FCM symptoms traceable to aSAH. We
23
decided to divide them into seven mutually exclusive groups (see Table 1). The groups were
24
designed as an ordered grading from most to least severe neuropsychiatric disability. A
25
dementia diagnosis was considered if MMSE was less than 25.
Mental Fatigability and MCI……
1

2
3
“Unassessable” patients had either severe dementia or severe aphasia, and were unable
to give a valid report of their problems.

Assessable patients with dementia, i.e. MMSE < 25 and impairments in personal and
4
instrumental ADL. Two of three patients also had multiple neurological deficits, but
5
only one a slight aphasia. Two of them also had a major depression.
6
12

Patients with Personality Change Due to a General Medical Condition had flattening
7
of affect or evidence of lasting personality changes according to interview with
8
relatives. Although this group may have anhedonia and be depressed, the most
9
common symptom for classifying them in this group was CPRS 45 (observed lack of
10
appropriate emotion). This group was labeled the “PCGMC” group. One patient had
11
MMSE 22 and all the others >=25. One patient had a slight aphasia. The PCGMC was
12
further subdivided into a combined group or after the dominating symptom or
13
according to DSM IV criteria.
14

Patients with anxiety or depressive disorders according to DSM IV (whether
15
medicated or not and including research criteria for minor depression). This group was
16
labeled the “depression/anxiety” group. No patient had neglect or aphasia. One patient
17
(an immigrant), had MMSE below 25.
18

Patients with a FCM index of “Mild” or worse. This group was labeled the “Pure
19
FCM” group. No patients had neglect or aphasia and only one (mild mental
20
retardation) had MMSE below 25.
21

“Miscellaneous” patients had problems not specified above. Two patients had mild
22
problems prior to the aSAH; one was recovering from a recent heart attack; and the
23
fourth patient had lasting neurological deficits without cognitive or psychiatric prob-
24
lems. No patient had an MMSE less than 25.
Mental Fatigability and MCI……
1

13
Finally, “Recovered” patients were judged to be GOS category 8 (Good Recovery,
2
High), i.e. full time working or no reduction of complex ADL activities. They
3
expressed no neurological, psychiatric, or FCM symptoms or signs. One patient
4
showed signs of cognitive reduction (MMSE 24), but neither the patient nor the
5
relative had noted any problems in the patient’s everyday life.
6
7
The Trail Making Test, with Extensions
8
TMT A and B were administered according to standard procedure (Lezak 1995)
9
complemented with written instructions by an experienced neuropsychologist. The outcome
10
variable was time until completion. If a test was discontinued for some reason, the patient was
11
not exposed to the more difficult TMT: s. The test was discontinued and considered failed,
12
when either five minutes had passed or the patient felt unable to continue. The pilot study
13
revealed no important differences between versions B and C (data not shown). Version D
14
(trial runs according to Figure 3) was constructed for use in this study and, mutatis mutandis,
15
administered with similar instructions. The B test was used as a template for the C and D
16
tests.
17
(Figure 3)
18
In TMT C, patients were instructed to draw lines between circles containing a member of
19
three different sets of ordered labels: numbers, letters and the names of the months in a cor-
20
rect order from the lowest (e.g. 1 to A to January) to the highest label. The new tests were
21
preceded by a trial run. Any errors made by a patient were indicated verbally to the patient,
22
but the correct solution was not revealed. Finally, errors observed by the investigator were
23
documented, as was the patient’s behavior. In TMT D, the order between the two first items
24
was exchanged, and weekdays were added to the series.
25
Mental Fatigability and MCI……
14
1
STATISTICAL METHODS
2
The variables assessed by scales were described by the median and 95% confidence interval
3
for proportion. Patient age was described by the median and inter-quartile range. Spearman’s
4
Rho was calculated as needed.
5
Cut-offs for TMT A and B were calculated using data from Tombaugh (2004). Since longer
6
times indicate poorer performance, an upper limit was defined as 1.5 SD above the mean
7
times given in that study. Patients with slower performance were judged to have failed the
8
test. In the absence of normative data for the new tests, the simpler pass/fail scoring was
9
chosen. The cumulative proportion of patients who failed in each group allows an evaluation
10
of the discriminative properties of the new tests.
11
12
Overall Hit Rate is widely used in neuropsychological literature (e.g. Stanczak 1998). The
13
Overall Hit Rate is the proportion of patients that perform as expected.
14
15
In this study, the expected pattern is that patients from the assessable dementia, PCGMC and
16
“Pure FCM” groups fail TMT C or D, while patients from the “Recovered” and
17
“Miscellaneous” groups should pass all tests. Patients from the “depression/anxiety” group
18
are expected to fail if they have an FCM score of “Mild” or worse.
19
20
To evaluate the classifications by the FCM Index we compared the individual’s FCM
21
category with the outcome according to the level of social function (GOS). The consistency in
22
the ordered distribution of pairs of outcomes (FCM Index, GOS) was expressed as the
23
monotonic agreement (Svensson 2000). This is a measure of order consistency based on the
24
difference between the proportions of concordant and discordant pairs of classifications,
25
adjusted for bivariate ties (i.e., observations are regarded as tied only for identical pairs of
Mental Fatigability and MCI……
15
1
observations.) Monotonic Agreement can take the values from -1 (totally reversed ordering of
2
all pairs) to 1 (total order consistency).
3
The Rank-Transformable Pattern (Svensson 2000) for the comparison of the two scales was
4
also displayed. This is the pattern of total order consistency given the marginal distributions
5
of the two scales. This allows the determination of cut-offs for corresponding categories
6
between two scales measuring the same variable.
7
8
ETHICAL APPROVAL
9
The study was approved by the Ethics Committee at Sahlgrenska University Hospital.
10
RESULTS
11
STUDY A
12
Study on reliability
13
Monotonic (inter-observer) agreement for FCM grading was 0.99 (0,5 % discordant pairs).
14
STUDY B
15
Studies of validity and prevalence
16
Symptoms
17
Of the eighty included patients, 50 (62.5 %; 95% CI 59 to 64 %) reported mental fatigability,
18
50 (62.5%; 95% CI 59 to 64%) reported concentration difficulties and 40 (50%; 95% CI 47 to
19
53%) reported memory impairment. Nineteen (24%; 95% CI 22 to 27 %) of the patients
20
reported none of the three symptoms (see Table 3 below). Inter-correlations between
21
symptoms varied between 0.39 (FM), 0.44 (CM) and 0.69(FC) (p<0,001).
22
Mental Fatigability and MCI……
16
1
We found no dominating FCM profile within the diagnostic groups in Table 1 (data not
2
shown).
3
4
5
FCM Index and eight-graded Glasgow Outcome Scale (GOS-8)
6
Monotonic agreement for the individual symptoms versus social outcome (GOS) were all
7
below 0, 9. Sixty-one (76%) of the 80 patients had an FCM score of “Mild” or worse. Figure
8
4 shows the frequency distribution of individual pairs of data from GOS-8 and FCM Index
9
assessments. Monotonic agreement between the FCM index and GOS-8, was 0.92 (i.e. 4% of
10
all unique pairs were discordant) and thus better than individual symptoms.
11
(Figure 4)
12
13
Shaded cells in Figure 4 indicate the rank-transformable pattern; i.e., the pattern of total order
14
consistency given the two sets of distributions of classification. This indicates corresponding
15
categories in the two scales. According to the Rank-Transformable Pattern, FCM “Severe”
16
corresponds to GOS-8 level “SD Low”; FCM “Moderate” corresponds to GOS-8 levels “SD
17
High”, MD “Low” and MD “High”; FCM “Mild” corresponds to GOS-8 levels “MD High”
18
and “GR Low”; and FCM “Asymptomatic” corresponds to GOS-8 levels “GR Low” and “GR
19
High”.
20
Monotonic Agreement for the subgroups was 1.00 (no discordant pairs) for “Pure FCM”
21
patients; 0.64 (18% discordant pairs) for patients with depression or anxiety, and 0.98 (1 %
22
discordant pairs) for those with Personality Change Due to a General Medical Condition. The
23
low value for Depressive Disorders is almost entirely due to two patients with Mb Bechterew
24
and severe neurological deficits respectively. Their conditions lower the social function
Mental Fatigability and MCI……
17
1
without lowering the cognitive function. If these patients are excluded the MA is 0. 97. MA
2
for the group “Assessable dementia” is not meaningful (only three patients).
3
4
For the distribution of FCM levels within each group, see table 2.
5
(Table 2)
6
7
FCM grade and MMSE
8
Median and interquartile range (IQ) MMSE values for the grades were FCM Asymptomatic:
9
29 (IQ 28 to 30), FCM Mild 29 (IQ 27.5 to 29) and FCM moderate 28 (IQ 27 to 30). The
10
patient with FCM severe had a value of 21. Monotonic agreement for FCM versus MMSE
11
score was 0.56, indicating 22 % discordant pairs.
12
13
Trail Making Test
14
Figure 5 shows the cumulative pass/fail proportions for patients from the “Recovered”, “Pure
15
FCM” and PCGMC group. Failure was defined as 1.5 SD above the norms given by
16
Tombaugh (2004) for tests A and B, and failure to complete within 5 minutes for tests C and
17
D.
18
(Figure 5)
19
For example, 16% of the patients in the “Pure FCM” group (3 of 19) failed the C test,
20
compared to 43% of the patients in the PCGMC group (10 of 23). Similarly, 3 of the 11
21
“Recovered” group failed the D test, compared to 11 of 19 (58%) in the FCM group.
22
23
Overall hit rate for all 80 patients was 26% for the A test, 49% for the B test, 40% for the C
24
test and 64% for the D test. Test D it is better than existing tests, despite the crude scoring
25
method.
Mental Fatigability and MCI……
18
1
2
No important differences between patients with minor and major depression with regards to
3
TMT performance were found.
4
5
All three patients from the “Recovered” group who failed the D test had less than nine years
6
of education. Two of them also had low MMSE scores (24 and 26), and the third was 74 years
7
old. Two patients in the FCM group failed the B test. One patient had had less than nine years
8
of education, and the other patient had been diagnosed with a mild mental retardation.
9
Fatigability Effect
10
The differences between test occasions were small, and no specific effect of mental
11
fatigability could be observed (data not shown).
12
Prevalence rates of FCM in other psychiatric disorders
13
Sixty-three of 80 patients presented with psychiatric symptoms. The overall prevalence rate of
14
FCM was 76 % (Table 2), but of those with FCM, 69 % occurred also had other psychiatric
15
co-morbidity. All but one of the patients diagnosed as having an Anxiety or Depressive (AD-
16
group) disorders also had FCM, in four of five cases of grade 2. The AD group consisted of 9
17
patients with minor depression, one patient with GAD and 14 patients with Major Depression.
18
The most heterogeneous disorder was the PCGMC, of which 20% (4 of 20) had FCM and
19
Anxiety or Depressive disorders, while 60% (12 of 20) had FCM only. Fifteen (3/20) percent
20
of the PCGMC lacked FCM, Anxiety or Depressive disorders. The PCGMC was subdivided
21
in 14 patients with apathy as the most prominent symptom and 6 patients had combined forms
22
of labile-aggressive and apathic types (one also had compulsive laughter). No patient of the
23
paranoid or disinhibited subtype was found in this series.
Mental Fatigability and MCI……
1
19
The co-morbidity of FCM in different psychiatric diagnosis is displayed in Table 3.
2
(Table 3)
3
We also performed a post-hoc analysis of MCI in the “pure FCM”, “depression/anxiety” and
4
PCGMC groups. We used the following MCI criteria: a) subjective complaints about
5
concentration difficulties or impaired memory; b) lowered social function (GOS 7 or less); c)
6
and objective evidence for difficulties on at least one of neuropsychological test (1.5 SD
7
above norms on TMT A or B), visuo-spatial difficulties (checked with MMSE) or aphasia
8
(checked with Boston Naming Test and MMSE).
9
According to these criteria, the MCI prevalence in the three groups was 32% (6 of 19;
10
FCM), 33% (8 of 24; depression/anxiety) and 55% (11of 20; PCGMC). There was no
11
difference in social outcome between patients with and without MCI in the FCM group.
12
Median GOS level for patients with MCI was somewhat lower in the depression/anxiety
13
group and the PCGMC group (5 versus 6 for those without MCI in both groups).
14
Comments
15
This study introduces two new concepts for the analysis of MCI and interactions with
16
psychiatric disorders: first, FCM index of reported cognitive dysfunction and second, an
17
Extension of the original Trail-Making Test.
18
19
Symptoms and status of FCM index
20
Of the 80 patients in this study, 62.5 % reported mental fatigability, 62.5 % reported
21
concentration difficulties and 50 % reported memory impairment. These figures are, in spite
22
of differences in patient selection and assessment methods, comparable to those in different
23
neuropsychological studies on aSAH (Ljunggren 1985, Hütter 1995, Hellawell 1999).
Mental Fatigability and MCI……
20
1
The FCM index is based on the hypothesis that these common symptoms are indicators of a
2
global brain dysfunction. The index might be viewed as an alternative to a sum score index,
3
which has an ambiguous interpretation and a Fatigability-Concentration-Memory (FCM)
4
profile, which is difficult to handle. As for the sum score, the symptoms are considered equal
5
indicators of the overall index and the number of possible profiles is reduced by the
6
requirement that the two worst symptoms should be entered (Figure 2). Thus, in this study,
7
the FCM is defined as a global cognitive index which is compared to global social function –
8
(GOS-8), global cognitive function (MMSE) and to neuropsychological function (Extended
9
TMT). Compared to MCI, this is a different approach in which one seeks a
10
neuropsychologically based subdivision of the MCI syndromes (Winblad 2004, Nordlund
11
2005). The intercorrelations between symptoms of FCM index indicates that the individual
12
symptoms contribute differently to the index, but the greatest overlap is between mental
13
fatigability and concentration difficulties. The specific information of for example memory
14
disturbances or mental fatigability can be investigated in a longitudinal study and might guide
15
the clinical symptoms defined for MCI. Furthermore, FCM might be defined as a subjective
16
cognitive dysfunction (Gauthier 2006, Petersen 2004) eventually preceding an objective
17
cognitive dysfunction as the definition of MNCD or MCI.
18
The high inter-observer agreement of FCM index (MA 0.99, i.e. only 0,5 % of assessments
19
was discordant between observers) in this study was unexpected, but might be explained by
20
the construction of FCM, where slight differences in assessment are cancelled out by the
21
definition of FCM grading (Figure 2).
22
FCM is part of constellation of symptoms which also includes sensory symptoms (Hellawell
23
1999, Rödholm 2001) and the relationship between these groups of symptoms must be
Mental Fatigability and MCI……
21
1
examined in longitudinal studies on aSAH. The interaction with emotional symptoms will be
2
discussed below.
3
FCM index and eight-graded GOS
4
GOS is the recommended scale for assessment of outcome after aSAH (van Gijn 1994) and
5
correspond to SOFAS in DSM IV. Definitions of grades are very similar. The choice of
6
twelve months as end-point was based on an earlier study (Svensson & Starmark 2002),
7
which showed an optimum of outcome assessment 6-12 months after aSAH.
8
9
The most heterogeneous FCM category, with regards to GOS score, was the “Moderate”
10
category. We believe that there are two principal reasons for this. Patients from all groups
11
with FCM (FCM group, PCGMC group, and depression/anxiety group) belonged to this cate-
12
gory. This means that the patients classified as “Moderate” are heterogeneous. Also, the sub-
13
jective experience of the cognitive dysfunction varies depending on the subject’s social and
14
medical context. As an example of this, the depressed patients had a higher proportion of
15
“Moderate” FCM but this might reflect their depressed mood.
16
17
Given the high agreement between FCM and GOS ( defined reduction 0of instrumental and
18
complex daily ADL activities, and capacity for work taken into account) (Figure 3), we
19
conclude that most of the information needed for the classification of social outcome after an
20
aSAH is acquired by combining the CPRS ratings of the two worst cognitive symptoms in the
21
manner described above (Figure 2). This might not be true for ordinary MCI groups which are
22
10-20 years older. However, care must be taken with patients lacking self-awareness of
23
symptoms in e.g. severe Personality Change or dementia. These patients may not be able to
24
give an accurate description of their problems and this information must be collected from
Mental Fatigability and MCI……
1
relatives or close friends as in this study. In patients with other diseases that reduce social
2
function the link between cognitive and social functions may be attenuated.
3
FCM and MMSE
4
MMSE did not discriminate between FCM-grades and this result is in agreement with other
5
studies on MCI (Steffens 2006).
22
6
7
FCM and the Extended Trail Making Test
8
The normal TMT is widely used to assess attention (Rabin 2005). Reitan and Wolfson
9
(Reitan 2004) state that it involves ”the use of symbols, the ability to deal effectively with
10
spatial configurations, and the ability to demonstrate flexibility in shifting between numbers
11
and letters while keeping both sequences in mind simultaneously”. A study of Index Medicus
12
and Psych Info revealed no other tests where extra series have been added to the original two.
13
The E-TMT differs from TMT B in that the number of sequences to be kept in mind is
14
greater, but there may be other factors that make E-TMT more sensitive to FCM symptoms.
15
16
A major finding of the study was that a large number of patients reporting FCM symptoms
17
were unable to finish the D test (and, to a lesser extent, the C test) within 5 minutes (Figure
18
5). The only patient from the “Recovered” group who failed the D test was old and was less
19
educated. The patients who had symptoms but passed the D test were younger and better
20
educated than those who failed, so the application of test in this group of patients will require
21
a comparison with a larger group of healthy controls in future studies. All this agrees well
22
with what is known about TMT A and B (Tombaugh 2004).
23
Mental Fatigability and MCI……
23
1
Our “hit rates” (69 % for the entire group) are similar to the hit rates reported for the standard
2
TMT, which varies from 63% (Stanczak 1998) up to 78% (Reitan 2004). The “pass/fail”
3
criterion used by us is rather conservative, and proper normative data (like those used for the
4
standard TMT) may improve the discriminative power of the test. The test misses patients
5
who are young and well educated. This is a common problem with neuropsychological tests,
6
and a single test can not be expected to give a perfect classification of brain-damaged and
7
normal subjects (Reitan 2004). It is not very specific (as shown by the misclassification of
8
patients with low MMSE or poor education), but this is not necessarily a weakness in a
9
screening test (Reitan 2004).
10
As could be expected, patients with Personality Change fail the test more often than those
11
without such problems. Emotional problems due to anxiety or depression do not seem to in-
12
fluence test performance, but since this is an exploratory study it is prudent not to draw any
13
definite conclusions.
14
Fatigability
15
The fatigability effect we looked for could not be demonstrated, and this is in agreement with
16
De Luca (De Luca 2005). This may be because the training effect is larger than we thought or
17
because the interview is not as tiring as we expected. It is also possible that TMT is not
18
sensitive to this effect. There may also be subgroups that show this effect, but our study was
19
too small to perform a detailed analysis.
20
21
FCM, Emotional Disorders MCI and Personality Change
22
In this study, 24 of 80 (30 %) patients were diagnosed as having a depressive and anxiety
23
disorders. Two of these cases also hade a Personality Change. (Table 3).Our prevalence of
Mental Fatigability and MCI……
24
1
depressive disorders agrees well with previous studies on other cohorts of aSAH ranging from
2
20-36 % (Carter, Morris). Nine patients were diagnosed as having a minor depression. The
3
proportion between minor and major depression (9 and 14 respectively) is similar to that
4
reported by Robinson 2003.
5
6
In the post-hoc analysis of MCI, we used information from symptoms, GOS, complex ADL-
7
activities, E-TMT, NIH Stroke Scale, Boston Naming test and MMSE. We can not exclude
8
the possibility that some patients might fail on other tests or show objective evidence of
9
fatigability on other tests. Moreover, this study cannot shed light on the problem of different
10
subgroups of MCI (Nordlund 2006).
11
The validity of TMT is shown by the literature (Rabin 2005), but our finding that the TMT A
12
and B did not discriminate between the groups might be problematic for a MCI diagnosis
13
based on TMT only. The results show that no dominating FCM profile provided further
14
information of subdivision of FCM and there were no differences in GOS and complex ADL
15
between the groups of FCM only and FCM+MCI. Patients with MCI and depression/anxiety
16
or PCGMC had a slightly worse social outcome, but the difference is small and may not be
17
statistically significant. It may also reflect our criteria, which use TMT to determine whether a
18
person has MCI or not. Together these results leads to the question if mental fatigability
19
should be included in future revisions of MCI criteria. Fatigue is already part of the diagnostic
20
criteria of postconcussional disorder. Winblad et al (2004) also discuss trauma as an etiology
21
of MCI.
22
An interesting finding in this study is that 23/24 patients diagnosed with depressive-anxiety
23
disorders and 16/20 patients diagnosed as having PCGMC also had FCM, in 60-80 % of
24
moderate severity (Tables 2 and 3). Thus, FCM might be seen as vulnerability factor for
25
depressive disorders. We don’t know any specific treatment for the FCM symptoms. The
Mental Fatigability and MCI……
25
1
implication might be that it is not possible to achieve complete remission of all symptoms
2
after proper treatment for depressive disorders. There is an earlier case report on this
3
phenomenon (Malmgren et al 2002). Future prospective studies are needed.
4
The proportion of Personality Change was 29 % in this material. Information from relatives
5
was necessary for diagnosis. Rödholm (2002) earlier reported that 36 % of his patients
6
showed evidence of PCGMC. The difference between studies can be attributed to differences
7
in patient selection (ISAT study) and in treatment (embolization).
8
We found no reports in the literature related to prevalence of depression or subtypes of
9
PCGMC.
10
11
Limitations
12
The pilot study on B & C (Table 1) did not reveal any important differences between TMT B
13
and C. A post-hoc control of bias did not reveal any important differences between this group
14
and the included group regarding, age, sex, and social outcome or MMSE distributions.
15
The main limitation of this study is a possible bias due to the fact that the same neuropsy-
16
chiatrist performed the clinical assessments GOS-8 levels and the checklist of complex ADL-
17
activities , MMSE and the E-TMT. Since the extended TMT was performed before the
18
clinical assessments, the results on the E-TMT may have influenced the assessment. The
19
findings must be replicated in a prospective blinded study. Second, many of the patients had
20
less than nine years of education. Since education is known to affect TMT performance as
21
well as MMSE performance ((Tombaugh 2004, Aevarsson ), it is reasonable to assume that
22
patients with a longer education may show superior performance in our patients (median age
23
55 yrs). The findings must be replicated in a prospective blinded study. Third, since this is a
24
cross-sectional study, it does not capture the temporal development of these disorders. Fourth,
Mental Fatigability and MCI……
26
1
we have no control group so we do not know how common FCM is in the population at large.
2
The use of norms (Tombough 2004) for TMT A and B versus a simple pass/fail score for
3
TMT C and D introduces a definitive bias and a drawback for the extensions. Bias from the
4
most clear cut cases of aphasia, extinction and/or neglect were avoided by using the combined
5
information from investigations with NIH Stroke Scale (Goldstein 1989) including the
6
Boston Naming Test (Kaplan 1983) and the MMSE item “copy a figure” (Folstein 1975).
7
8
Mental Fatigability and MCI……
27
1
REFERENCES
2
Ljunggren B, Sonesson B, Säveland H, Brandt L. Cognitive impairment and adjustment in
3
patients without neurological deficits after aneurysmal SAH and early operation. J Neurosurg
4
1985; 62:673-9.
5
6
Hütter BO, Gilsbach JM, Kreitschmann I. Quality of life and cognitive deficits after su-
7
barachnoid hemorrhage. Br J Neurosurg 1995; 9:465-75
8
9
10
Hellawell DJ, Taylor R, Pentland B. Persisting symptoms and carers’ views of outcome after
subarachnoid haemorrhage. Clin Rehabil 1995; 13:333-340.1.
11
12
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders,
13
Fourth Edition. Washington, DC, American Psychiatric Association, 1994.
14
15
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S,
16
Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M,
17
Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B; International Psychogeriatric
18
Association Expert Conference on mild cognitive impairment. Mild cognitive impairment.
19
Lancet. 2006;367(9518):1262-70.
20
21
Petersen RC, O'Brien J. Mild cognitive impairment should be considered for DSM-V. J
22
Geriatr Psychiatry Neurol. 2006; 19:147-54
23
24
25
Mental Fatigability and MCI……
28
1
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A,
2
Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C,
3
Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser
4
P, Petersen RC. Mild cognitive impairment--beyond controversies, towards a consensus:
5
report of the International Working Group on Mild Cognitive Impairment. J Intern Med.
6
2004; 256:240-6.
7
8
Rödholm M, Hellström P, Bilting M, Starmark J-E. Diagnostic classification of organic
9
psychiatric disorders after aneurysmal subarachnoid hemorrhage: a comparison between ICD
10
DSM-IV and the Lindqvist & Malmgren classification system. Acta Psychiatr Scand 2003;
11
108: 222-31.
12
13
De Luca J: Fatigue, Cognition and Mental Effort. In de Luca J, ed. Fatigue as a Window to
14
the Brain. Cambridge, Mass, MIT Press. 2005; pp 37-57.
15
16
Rödholm M, Starmark J-E, Svensson E, von Essen C. Astheno-emotional disorder after aneu-
17
rysmal SAH: reliability, symptomatology and relation to outcome; Acta Neurol Scand 2001;
18
103:379-85
19
20
van Gijn J, Bromberg JE, Lindsay KW, Hasan D, Vermeulen M. Definition of initial
21
grading, specific events, and overall outcome in patients with aneurysmal subarachnoid
22
hemorrhage. A survey. Stroke. 1994; 25:1623-7
23
Mental Fatigability and MCI……
29
1
Perneczky R, Pohl C, Sorg C, Hartmann J, Tosic N, Grimmer T, Heitele S, Kurz A.
2
Impairment of activities of daily living requiring memory or complex reasoning as part of the
3
MCI syndrome. Int J Geriatr Psychiatry. 2006; 21:158-62.
4
5
Reitan RM, Wolfson D. The Trail Making Test as an initial screening procedure for neuro-
6
psychological impairment in older children. Arch Clin Neuropsychol 2004; 19:281-8
7
8
Rabin LA, Barr WB, Burton LA. Assessment practices of clinical neuropsychologists in the
9
United States and Canada: a survey of INS, NAN, and APA Division 40 members. Arch Clin
10
Neuropsychol. 2005; 20: 33-65.
11
12
Tranel D, Bechara A, Damasio A R. Decision Making and the somatic marker hypothesis. In
13
Gazzaniga M S, ed. The New Cognitive Neuroscience. Cambridge, Massachusetts: MIT
14
Press; 2000. p.1047-1061.
15
16
Steffens DC, Otey E, Alexopoulos GS, Butters MA, Cuthbert B, Ganguli M, Geda YE,
17
Hendrie HC, Krishnan RR, Kumar A, Lopez OL, Lyketsos CG, Mast BT, Morris JC, Norton
18
MC, Peavy GM, Petersen RC, Reynolds CF, Salloway S, Welsh-Bohmer KA, Yesavage J.
19
Perspectives on depression, mild cognitive impairment, and cognitive decline. Arch Gen
20
Psychiatry. 2006; 63:130-8
21
22
Carter BS, Buckley D, Ferraro R, Rordorf G, Ogilvy CS. Factors associated with
23
reintegration to normal living after subarachnoid hemorrhage. Neurosurgery. 2000; 46:1326-
24
33
25
Mental Fatigability and MCI……
30
1
2
Morris PG, Wilson JT, Dunn L. Anxiety and depression after spontaneous subarachnoid
3
hemorrhage. Neurosurgery. 2004; 54:47-52
4
5
Molyneux A, Kerr R, Stratton I et al. International Subarachnoid Aneurysm Trial (ISAT)
6
Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical
7
clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a
8
randomised trial. Lancet 2002; 360 (9342):1267-1274.
9
10
Folstein MF, Folstein SE, McHugh PR. "Mini-Mental-State". A practical method for grading
11
the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189-98.
12
13
Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH Stroke Scale. Arch
14
Neurol 1989; 46:660-2.
15
Kaplan, E. & Goodglass, H. Boston Naming Test. Philadelphia: Lea & Febiger. 1983.
16
Spitzer RL, Williams JBW, Gibbon M, First MB. The structured clinical interview for DSM-
17
III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 1992; 49:624-629.
18
19
Åsberg M, Montgomery SA, Perris C, Schalling D, Sedvall G. A comprehensive
20
psychopathological rating scale. Acta Psychiatr Scand Suppl 1978; 271:5-27.
21
22
Svanborg P, Åsberg M. A new self-rating scale for depression and anxiety states based on
23
the Comprehensive Psychopathological Rating Scale. Acta Psychiatr Scand. 1994; 89:21-8.
24
Mental Fatigability and MCI……
1
Rödholm M. Astheno-Emotional Disorder after Aneurysmal Subarachnoid Haemorrhage.
2
Classification, outcome, and relation to anxiety and depressive disorders. (Dissertation).
3
Göteborg: Göteborg University; 2003.
31
4
5
Svensson E, Starmark JE. Evaluation of individual and group changes in social outcome after
6
aneurysmal subarachnoid haemorrhage: a long-term follow-up study. J Rehabil Med. 2002;
7
34:251-259.
8
9
10
Jennett B, Bond M. Assessment of outcome after severe brain damage. A practical scale.
Lancet 1975; i:480-4.
11
12
Lezak MD: Neuropsychological assessment. 2nd Edition. Oxford University Press, Oxford,
13
1995.
14
15
Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education
16
Arch Clin Neuropsychol. 2004; 19:203-14.
17
18
Stanczak DE, Lynch MD, McNeil CK, Brown B. The expanded Trail Making Test: rationale,
19
development, and psychometric properties. Arch Clin Neuropsychol. 1998; 13:473-87.
20
21
Svensson E. Concordance between ratings using different scales for the same variable. Stat
22
Med 2000; 19:3483-3496.
23
24
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256:183-
25
94
Mental Fatigability and MCI……
32
1
2
Nordlund A, Rolstad S, Hellstrom P, Sjogren M, Hansen S, Wallin A. The Goteborg MCI
3
study: mild cognitive impairment is a heterogeneous condition. : J Neurol Neurosurg
4
Psychiatry. 2005; 76:1485-90
5
6
Robinson RG. Poststroke depression: prevalence, diagnosis, treatment, and disease
7
progression. Biol Psychiatry. 2003; 54:376-87
8
9
Malmgren K, Starmark JE, Ekstedt G, Rosen H, Sjoberg-Larsson C. Nonorganic and
10
Organic Psychiatric Disorders in Patients after Epilepsy Surgery. Epilepsy Behav. 2002; 3:67-
11
75.
12
13
Rödholm M, Starmark JE, von Essen C. Organic psychiatric disorders after aneurysmal
14
SAH: outcome and associations with age, bleeding severity, and arterial hypertension. Acta
15
Neurol Scand 2002: 106: 8-18.
16
17
Aevarsson O, Skoog I. A longitudinal population study of the mini-mental state examination
18
in the very old: relation to dementia and education. Dement Geriatr Cogn Disord. 2000;
19
11:166-75.
20
21
22
23
Mental Fatigability and MCI……
Figure legends
Figure 1. Order of investigations.
Figure 2. Fatigability-Concentration-Memory (FCM) Index. A= Asymptomatic, Mi= Mild,
Mo= Moderate, S=Severe
Figure 3
Trial Runs for Trail Making Tests C and D
Figure 4
Frequency table for paired assessments with the FCM Index and GOS. Asympt =
Asymptomatic. SD = Severe disability. MD = Moderate Recovery. GR = Good Recovery.
Figure 5
Cumulative Failure on Extended TMT
33
Mental Fatigability and MCI……
34
FIGURE 1
Basic Demographic Data
TMT
Battery
Baseline
MMSE
Cognitive Function
NIHSS
BNT
Neurology
SCID
CPRSItems
Psychiatry
GOS
Complex
ADL
TMT
Battery
Social Function
Fatigability
Mental Fatigability and MCI……
35
FIGURE 2
Item 1
FATIGABILITY-CONCENTRATION- MEMORY (FCM) INDEX
3
MO
MO
MO
S
S
S
S
2,5
MO
MO
MO
MO
S
S
S
2
MO
MO
MO
MO
MO
S
S
1,5
Mi
Mi
Mi
MO
MO
MO
S
1
Mi
Mi
Mi
Mi
MO
MO
MO
0,5
R
Mi
Mi
Mi
MO
MO
MO
0
R
R
Mi
Mi
MO
MO
MO
0
0,5
1
1,5
2
2,5
3
Item 2
Mental Fatigability and MCI……
36
FIGURE 3
SAMPLES OF TRAIL MAKING TESTS C AND D
Mental Fatigability and MCI……
37
FIGURE 4
INTER-SCALE AGREEMENT FOR THE FCM INDEX AND GOS-8
FCM
Recovered
Mild
Moderate
SD low
1
SD high
3
MD low
1
1
11
MD high
1
6
24
GR low
6
10
2
GR high
11
2
Severe
1
Mental Fatigability and MCI……
38
FIGURE 5
Recovered (n=11)
FCM (n=19)
A
B
Depression (n=24)
PCGMC (n=20)
1
Proportion
0,75
0,5
0,25
0
Test
C
D
Mental Fatigability and MCI……
39
TABLE 1
DEMORAPHIC DATA
n
F
Median age
(quartiles)
A. Reliability Study *) †
32
B.Validity/Prevalence Study Admitted
162
24
53 (46 to 59)
55 (51 to 62)
Deceased
24
Refused
13
Incomplete data: Dementia and aphasia (n=15), TMT
45
37
80
57
Assessable dementia‡
3
2
43, 44, 67
PCGMC
20
12
59 (52 to 64)
Depression, anxiety
24
19
52 (48 to 58)
Fatigability-Concentration-Memory only
19
13
55 (42 to 58)
Miscellaneous ‡
3
2
21, 47, 60
Asymptomatic and restored social function
11
9
53 (44 to 56)
not done (n=5), Pilot study on TMT B and C (n=25)
Groups included in analysis
*) Four patients were assessed twice at different times
Table 1. Summary of patients included in the study on cognitive symptoms. n = number of patients; F = number
of females; PCGM = Personality Change Due to a General Medical Condition. †Rödholm 2001. ‡Since there
are only three patients in these groups, all data are given.
Mental Fatigability and MCI……
40
TABLE 2
FATIGUE-CONCENTRATION-MEMORY INDEX IN PSYCHIATRIC DISORDERS
Diagnosis
FCM Score
Asympt.
Mild
Moderate
Severe
“Pure” FCM (n=19)
0%
58%
42%
0%
Depression/Anxiety (n=24)
4%
16%
79%
0%

minor depression (n=9)
0%
22%
78%
0%

major depression (n=14)
7%
14%
78%
0%

GAD (n=1)
0%
0%
100%
0%
20%
20%
60%
0%
PCGMC (n=20)

Combined form (n=6)
0%
33%
57%
0%

Apathic form (n=14)
29%
14%
66%
0%
0%
0%
67%
33%
Dementia (n=3)
Table 2. FCM = Fatigue-Concentration-Memory index; Asympt.= Asymptomatic; GAD = Generalized Anxiety
Disorder; PCGMC = Personality Change due to a General Medical Condition. Note that some groups are very
small, so percentages need to be carefully interpreted.
Mental Fatigability and MCI……
41
Table 3
DIAGNOSIS DISTRIBUTION (N=80)
n
Recovered
Miscellaneous
Pure FCM
Depression
 minor
 major
 GAD
PCGMC
 Combined
 Apathetic
Dementia
11
3
19
24
9
14
1
20
6
14
3
No
Comorbidity
11
3
19
1
0
1
0
3
0
3
0
+FCM
+ Depr.
23
9
13
1
12
6
6
1
1
0
1
0
+FCM
+Depression
4
0
4
2
Table 3:
Diagnosis distribution for all patients. FCM = FATIGABILITY-CONCENTRATION- MEMORY (FCM) INDEX , GAD =
Generalized Anxiety Disorder; PCGMC = Personality Change due to a General Medical Condition.
Mental Fatigability and MCI……
42