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Memory Components
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Spaan, Raaijmakers, and Jonker, Neuropsychology, Vol…………
Appendix A: More Detailed Methodological Information
Participants
Subjects were selected from the Longitudinal Aging Study Amsterdam
(LASA), a large-scaled population-based study of elderly individuals with the
objective of determining the predictors and consequences of changes in physical,
cognitive, emotional and social functioning in elderly people (Deeg, Beekman,
Kriegsman & Westendorp-De Serière, 1998). In 1992/1993, the first cycle of
interviews and (medical) examinations took place; every three years the participants
were invited to participate in a new cycle. The LASA participants had given informed
consent to volunteer in additional studies coordinated by LASA, such as the study
described in this paper.
At T1, recent LASA data (from the third cycle held in 1998/1999) were used to
select subjects for the current research. All subjects were community dwelling elderly
people. First, the LASA participants were screened for depression by means of the
‘Center for Epidemiologic Studies Depression Scale’ (CES-D; Radloff, 1977).
Participants scoring 16 or above were excluded (Beekman et al., 1997). Secondly, the
participants were screened for Cerebrovascular Accidents (CVA). Participants were
excluded if they ever experienced a CVA.
In addition, in order to create a cognitively heterogeneous sample at T1 (which
should result, at T2, in as many demented subjects as possible), two subgroups were
created according to their global level of cognitive functioning, measured by the Mini-
Mental State Examination (MMSE; Folstein, Folstein & McHugh, 1975): the
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cognitively impaired (CI) group and the normal control (NC) group. The CI group
scored in the 21-25 range of the MMSE. The NC group scored in the 27-30 range of
the MMSE1. A systematic decision procedure was constructed, which included two or
three administrations of the MMSE (obtained from T1, the third LASA cycle and, if
these were discrepant, the second cycle three years before). In this way, each subject
was classified to the most representative subgroup and the most consistent score was
determined (see Appendix B for details). This procedure takes into account the fact
that the MMSE score is not 100% reliable. CI subjects were matched to NC subjects
for age, years of education, and sex.
Additional data derived from recent LASA data showed that the subjects
screened for the CI group performed significantly worse than the NC subjects on three
available different cognitive measures: the 15 Words Test (similar to the Auditory
Verbal Learning Test, delayed recall; p=.010), the Coding Task (similar to WAIS
Digit Symbol, measuring information processing speed; p<.001), and the Raven
Coloured Progressive Matrices (measuring nonverbal abstract reasoning ability;
p<.001). The CI group is supposed to be at risk for developing dementia (within a few
years). The NC group is supposed to be cognitively intact.
The CI subjects might be interpreted as suffering from Mild Cognitive
Impairment (MCI). The corresponding criteria proposed by Petersen et al. (1999) are:
(1) subjective memory impairments, preferably corroborated by an informant, (2)
objective memory impairment, when compared with persons of similar age and
education, (3) ‘normal’ general cognitive function (although processing speed and
cognitive flexibility may be impaired as well (Petersen, 2000)), (4) normal activities
of daily living (ADL), and (5) not demented. The only criterion that we cannot meet
in our study is the first one regarding the subjective memory impairment since we do
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not have systematic information on this criterion. Although subjective memory
complaints were (not surprisingly given the nature of this group) frequently voiced
when subjects were initially tested, no systematic questionnaire was administered that
might have measured the existence of subjective memory complaints in a valid and
reliable way. Thus, strictly speaking, the CI group does not officially meet the MCI
criteria, though there will be a high resemblance (most likely similar to the ‘Multiple
Cognitive Deficits’-type; e.g., Lopez et al., 2003a, 2003b; Busse, Bischkopf, Riedel-
Heller & Angermeyer, 2003). Therefore, we will apply the descriptive term
‘cognitively impaired’ (CI) instead of MCI, which is associated with Petersen’s
criteria.
At T1, all subjects should be non-demented, in order to be able to examine
preclinically demented cases. Because the MMSE is merely a cognitive screening
measure, the at risk group of CI subjects was additionally administered a validated
short version of the Cambridge Examination for Mental Disorders of the Elderly
(CAMDEX; Neri, Rubichi, DeVreese, Roth & Cipolli, 1998). Thus, demented
subjects (n=7) and subjects with other neurological or psychiatric causes of cognitive
dysfunctioning were excluded. This instrument provides for a dementia diagnosis
consistent with the DSM-IV criteria. It consists of an extensive cognitive/memory
section (the CAMCOG) and other questions related to the DSM-IV criteria. In
addition, subjects who were not able or willing to continue the test administration
were excluded (n=4; excluding also non-native Dutch speakers). Ultimately, at T1,
valid and complete data sets were available for 119 clinically non-demented subjects:
51 CI subjects and 68 NC subjects.
These subjects were approached for a second test two years after the initial
administration of the memory test battery (T2). Subjects who had died or had become
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physically (e.g., deaf, blind, suffered from CVA or were otherwise seriously ill) or
mentally (e.g., seriously depressed) incapable to participate in the second
administration (according to recent LASA data) were not approached. Ultimately,
valid and complete data sets were available for 96 subjects at T2 (43 CI ss. and 53 NC
ss.).
In addition to the repeated administration of the memory test battery, the
CAMDEX was re-administered in order to determine the subjects that had developed
dementia in the intervening period (i.e., CAMDEX diagnosis ‘mild/moderate
dementia’; n=6). Furthermore, the general practitioner (GP) of the subjects that
dropped out at T2 was asked whether the particular subject had become demented in
the past two years according to the official medical records (resulting in three
additional demented cases). All of these 9 subjects that turned out to be demented at
T2 originated from the CI group created at T1 (i.e., CI subjects who had developed
dementia at T2). In this way, three clinical subgroups were obtained, based on the
dementia assessment at T2 and screening of cognitive performance at T1:
(1) Normal Control (NC; n=68): no cognitive dysfunctions, intact ADL functioning,
not demented, not depressed, no CVA history.
(2) Cognitively Impaired (CI; n=42): various cognitive dysfunctions (i.e., MMSE,
delayed recall, processing speed, nonverbal abstract reasoning ability), but intact
ADL functioning and not demented, not depressed, no CVA history. Considered
to be at risk for developing dementia in the (near) future.
(3) (Pre)clinically Demented (PCD; n=9): various cognitive dysfunctions, intact ADL
functioning and not demented at T1, but diagnosed as demented according to
DSM-IV criteria at T2 – preclinically demented (PCD) at T1; clinically demented
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(CD) at T2 (most likely cause: Alzheimer’s Disease considering the absence of
CVA history or depression).
See Table 1 in main manuscript for further characteristics (demographic and
screening variables) of these three clinical subgroups.
In addition, the characteristics of the group of subjects that were re-tested at T2
(n=96) were compared with the characteristics of the subjects that dropped out at T2
(n=23). The only difference between these two groups was that the dropped out
subjects, with a mean age at T1 of 82.00 years (SD 6.58), were significantly older than
the at T2 re-tested subjects (mean age 78.10 (SD 8.45); p=.008).
General Procedure
At T1, an appointment for the memory test administration was made with the
LASA participants that conformed to the inclusion and exclusion criteria after they
had given informed consent. The administration of the memory test battery took place
in the home environment of the subject by means of a laptop computer. The test
administration was conducted by a neuropsychologist (P.E.J.S.), who operated the
computer (i.e., the subject only had to look at the screen on which the stimuli were
presented). The instructions (for each subtest) were presented orally. The subject was
explained beforehand that distracting circumstances had to be avoided in order to
concentrate well (noises of TV, telephone, inexpected visitors, etc.). Since there were
many short breaks between subtests (or between different trials), interruptions hardly
ever occurred during testing. If performance was clearly affected by an occasional
interruption, the particular subtest data were indicated as ‘missing values’. Subsequent
to the memory test administration, the CI subjects were informed that they would be
visited by a physician, who administered the short version of the CAMDEX (Neri et
al., 1998). This visit took place within six weeks of the memory test administration.
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Two years later, the subjects that were still available at T2 were invited for the
second administration phase. The repeated administration took place, on average,
103.47 weeks (SD 3.88) after the first administration of the memory test battery (95-
122 weeks). The procedure of the test administration at T2 was identical to the
procedure at T1, except for the additional administration of the CES-D and questions
regarding CVA in order to control for these variables (as was done at T1).
In addition, the subjects scoring 26 or below on the MMSE, administered at
T2, were visited by the physician who administered the validated short version of the
CAMDEX in order to identify the subjects that had become clinically demented in the
past two years. Subjects who scored 27 of above on the MMSE were considered not
to be demented (i.e., the same procedure was applied at T1). However, subjects who
scored 27 or above and, nevertheless, demonstrated cognitive deficits that caused
doubts about their non-demented status were visited by the physician as well. This
procedure made sure that no demented cases were missed. All subjects that were
administered the CAMDEX were discussed with an experienced neurologist (C.J.),
who was responsible for the final assessment.
Since it was not possible to conduct a physical examination, the diagnosis
simply said ‘demented’ or ‘not demented’, rather than a specification of the type of
dementia. The CAMDEX did specify the severity of the disease: ‘minimal’, ‘mild’,
‘moderate’ or ‘severe’ dementia. In mild, moderate and severe dementia, all of the
DSM-IV criteria of dementia are satisfied (i.e., the PCD group in the current
research). In minimal dementia, the DSM-IV criteria are not satisfied, because (1) no
additional cognitive deficits are observed (only (‘episodic’) memory impairments are
found), and (2) cognitive deficits do not cause evident impairment in occupational or
social functioning. Therefore, subjects with a ‘minimal dementia’ diagnosis were
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classified as ‘non-demented’ (all originated from the CI group). See Roth et al. (1986)
for more detailed information. It may be argued that the subjects with a ‘minimal
dementia’ classification meet criteria for the MCI ‘amnestic’-type (e.g., Lopez et al.,
2003a, 2003b; Busse et al., 2003; Luis et al., 2004). These subjects are, however, not
presented as a separate group because the category seems rather unstable regarding
conversion to dementia (see Appendix B for details).
Material
Memory Test Battery
The memory tests were administered by means of an Apple PowerBook laptop
computer with an 11.3” active-matrix colour screen (800x600 resolution). Below, the
subtests will be described in the same order as they were presented in the battery.
Ten word list-learning test.
Ten semantically unrelated but concrete imaginable words (nouns) were
consecutively presented on the screen (2 s each; interval 0.5 s), in three trials
presenting the same words but in a different sequence (in order to prevent sequential
effects at free recall). Between presentation and recall phase, a three-digit number was
presented on the screen for 20 seconds, from which the subject had to count
backwards by steps of three. This task was aimed at distracting the subject in order to
prevent recency effects, thus, measuring retrieval from long-term store rather than
from short-term store. The total number of words reproduced over three trials was
used as the main score of this subtest in data analyses (range of scores: [0, 30]).
Digit span task.
After a fixation point (1 s) in the middle of the screen, random digits (varying
from 1 to 9) were consecutively presented on the screen (1 s each; interval 1 s).
Logical sequences of digits were excluded. Immediately after presentation, the subject
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had to orally reproduce the digits in the same order as they were presented on the
screen. The actual task of 10 trials was preceded by two practice trials, both starting
with a four-digit-sequence. Subsequent to a correct response, the next trial presented a
one-digit-more-sequence; subsequent to a wrong response, the next trial presented a
one-digit-less-sequence (ranging between 1- and 10-digit-sequences). The longest
sequence correctly reproduced was not selected as the main ‘digit span’-score,
because this score might not be a representative measure when it occurred only once
or twice in 10 trials. Instead, a span score was computed that was less susceptible to
chance: (1) the longest sequence presented on three or more trials, of which at least
50% of the sequences was correctly reproduced, or (2) the longest sequence presented
on two trials, if both sequences were correctly reproduced.
Word-recognition test (yes/no).
In this subtest, the words from the ‘Ten word list-learning test’ (the ‘targets’)
had to be recognised (by answering ‘yes’ or ‘no’) from a list that also included 10
words not presented previously but semantically related to the targets (the
‘distractors’; matched to the targets for word length). The subject was not alerted to
the semantic relation between the targets and the distractors. Main score: total of
correct decisions (true positive and true negative answers). Range: [0, 20].
Paired-associate learning test.
This subtest was administered according to the same format as the ‘Ten word
list-learning test’, except for the presentation of 10 word pairs (instead of 10
unrelated, separate words). Five pairs were semantically related, the other five were
unrelated (each presented for 3 s; interval 0.5 s); the subject was not alerted to the
semantic relation of the word pairs. Semantic associations between words were
derived from Dutch word association norms (De Groot, 1980; Van Loon-Vervoorn &
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Van Bekkum, 1991). During recall phase, the cues (i.e., the first word of each pair)
were presented in random order. Main score: total of word pairs reproduced over three
trials. Range: [0, 30].
Block span task.
This test is the visuospatial variant on the ‘Digit span task’ (i.e., the same
procedure and the same specific ‘span’-score were applied). Ten square-fields
(‘blocks’) were presented on the screen like the black squares of a chessboard. A
sequence of random blocks flashed consecutively (by turning into black on the white
background; for 1 s each; interval 1 s). Immediately after presentation, the subjects
had to reproduce the sequence by indicating the correct blocks in the correct sequence
at the screen.
Word stem completion task.
Two- or three-letter word stems were consecutively presented on the screen.
For each stem, the subject had to name a word that started with the letters presented
and was the first (Dutch) word that came to mind. This word should add a minimum
of two letters to the presented stem. The test consisted of 10 ‘experimental’ stems –
which could be completed with the words from the ‘Ten word list-learning test’ – and
10 ‘control’ stems, which referred to words that were not presented before. The 20
‘target words’ were selected from a list of word stem completion norms (Phaf &
Wolters, 1991). Words were selected that were not frequently named (twice in 200
completions), in order to reduce the possibility of spontaneous completion. The
experimental and control stems were matched for the number of different words
named for each stem, the number of incorrect words named for each stem and length
of the corresponding target. The subject was not alerted to the relation of this task
with the ‘Ten word list-learning test’. None of the words that were presented in
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previous subtests could complete the stems used in this task. Main score: number of
experimental stems that were completed with a target word minus number of control
stems that were completed with a target word. Range: [-10, 10].
Category fluency test.
The categories ‘animals’ and ‘occupations’ were used. The subject had to
name as many exemplars that belonged to these categories as he could think of within
60 seconds per category. All responses were judged on whether they represented
unique exemplars of the category. Incorrect responses were: repeated responses,
perseverations on previous responses (that represent the same category exemplar, e.g.,
sex-specific and age-specific names of the same animal species), and intrusions (i.e.,
no valid members of the category). Main score: sum of correct animals and correct
occupations that were generated within 60 seconds each.
Mirror-reading task.
Sixty mirror-words were consecutively presented on the screen. The letters
were rotated on the vertical axis. The words had to be read from right to left and were
presented in capital letters2. The subject had to read each word as quickly as possible
without making mistakes. Each stimulus was presented on the screen until the subject
had generated a response. Two practice trials were given in advance. The six blocks
of 10 consecutively presented words (in order to analyse practice effects of mirror-
reading during the task) were matched for word length. Main score: mean reading
time (in seconds) over all correctly read mirror words.
Perceptual identification task.
After a fixation point (1 s) in the middle of the screen, the subject had to
identify words that were briefly presented on the screen, as quickly as possible, by
reading them aloud. Every word was repeatedly presented in ‘tics’ of 16 msec: each
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consecutive presentation of a word lasted one tic longer (it started at two tics and
ended at a maximum of 20 tics). Before and after each presentation of the word, a
mask (XXXXXXXX) was presented for five tics consistently. When the subject
identified the word correctly, the word was clearly presented for 1 s. This was done
because 12 words were presented in another trial as well – in order to be able to
measure the effect of repetition (the perceptual priming effect), the subject must have
had the opportunity to encode the word sufficiently. The subject was not alerted to the
repeated presentation of words in order to prevent explicit remembering. Three
practice trials were given in advance. The test consisted of a total of 48 words, among
which 12 low-frequency (‘LF’) words, 12 middle-frequency (‘MF’) words, 12 high-
frequency (‘HF’) words and 12 repeated presentations of the middle-frequency words
(‘rep-MF’). The word frequencies were derived from the CELEX database (CELEX
Dutch Database Release N31, 1990). The three groups of different words (LF, MF,
HF) were matched for word length. In order to control for practice effects, the
presentation procedure comprised three blocks of 16 words, each block consisting of
four words of each condition (LF, MF, HF, rep-MF). The three blocks were matched
for word frequency, word length and the number of words presented between a MF
word and its repeated presentation. Main ‘semantic memory’ score: mean reaction
time (in tics of 16 ms) over all HF, MF and LF words. Main ‘priming’ score: mean
reaction time (in tics of 16 ms) over the MF words minus mean reaction time over the
rep-MF words.
Two-alternative word-recognition test.
Two words were simultaneously presented on the screen: one was a word from
the ‘Ten word list-learning test’ (a ‘target’) and the other was its semantically related
distractor (the same distractors as in the ‘Word-recognition test’). The subject had to
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recognise the targets (randomly presented on the left or the right of the screen), thus,
measuring delayed recognition. Main score: total of correct decisions (recognised
targets). Range: [0, 10].
Visual Association Test
This test was developed by Lindeboom (Lindeboom, Schmand, Tulner,
Walstra & Jonker, 2002) with the purpose to detect serious (episodic) memory
disorders in elderly persons of 65 years and older, which might be associated with
dementia. This test was additionally administered in the current research in order to
investigate its predictive value with regard to dementia. Six line drawings of common
objects (the ‘cues’; e.g., a chair) were presented. The subject had to name them (aided
by the experimenter if necessary). Subsequently, the same six line drawings were
presented with the addition of a second object (the ‘targets’: e.g., a hedgehog was
sitting on the chair), which the subject also had to name. In the final trial, the original
line drawings (the cues) were presented; the subject had to recall the targets. All
drawings were illogical combinations of (interacting) objects. Main score: total of
target objects that were recalled. Range: [0, 6].
References
CELEX Dutch Database Release N31. Computer Software, Nijmegen: Centre
Lexical Information, 1990.
Groot, de, A. M. B. (1980). Mondelinge woordassociatienormen: 100
woordassociaties op 460 Nederlandse zelfstandige naamwoorden [Oral word
association norms: 100 word associations to 460 Dutch nouns]. Lisse: Swets &
Zeitlinger.
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Loon-Vervoorn, van, W. A., & Van Bekkum, I. J. (1991). Woordassociatie
lexicon: Gebaseerd op 1299 woorden en 100 proefpersonen [Word association
lexicon: Based on 1299 words and 100 subjects]. Amsterdam/Lisse: Swets &
Zeitlinger.
Molster, F., & Koekkoek, M. (1997). Meting van het geheugen bij ouderen:
Afname en evaluatie van een verbeterde en aangepaste versie van een
geautomatiseerde geheugentestbatterij [Measurement of memory in elderly:
Administration and evaluation of an improved and adapted version of a computerised
memory test battery]. Unpublished master’s thesis, University of Amsterdam,
Amsterdam.
Phaf, R. H., & Wolters, G. (1991). Spontane aanvulfrequenties voor 168 twee-
en drieletterige woordstammen [Spontaneous completion frequencies for 168 two-
and three-letter word stems]. Internal report, University of Leiden, Leiden.
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Appendix B: Flow Sheet of the Sampling and Testing Protocol
7 prevalent demented
(CAMDEX)
65 CI (based on 2 or 3 MMSE scores*)
82 NC(based on 2 or 3 MMSE scores*)
excluded
4 unwilling or unable to complete test administration
Second screening phase: after CAMDEX and MMSE* administration at T1:
excluded
51 CI 68 NC
Third screening phase: for selecting ss. for analyses presented in current paper: excluding ss. with missing values on 1 subtests and ss. that ever experienced a CVA;& Additional analyses: LASA 3rd cycle data: CI < NC on 3 cognitive measures: 15 Words Test (delayed recall; p=.010), Coding Task (p<.001), Raven CPM (p<.001): CI MCI-‘multiple cognitive deficits’-type;
43 CI 53 NC
Available ss. at second test, 2 years later (T2):
6 converted to dementia (CAMDEX)
3 converted to dementia (GP)
9 Preclinically Demented (PCD)
at T1
42 CI (at T1; at T2 (still) non-
demented)68 NC
* according to systematic decision procedure: if MMSE from LASA 3rd cycle and MMSE from T1 are discrepant (e.g., LASA3: 27, T1: 24), then MMSE from LASA 2nd cycle (‘95/’96) determines the final group classification (NC or CI). Final MMSE score that is applied for analysis in the current paper is equal to the T1 MMSE score if T1 MMSE score and LASA 3rd cycle score are not discrepant (i.e., are both within same range of 21-25 or 27-30 respectively); or equal to average of T1 MMSE score and LASA 3rd cycle score if these scores are discrepant.
15 NC dropped out
Available for analyses (using T1 data):
First screening phase: according to LASA 3rd cycle data (1998/1999; n=1872), for selecting ss. for T1
baseline administration of Memory Test Battery (in 1999/2000): CES-D < 16 (exclusion of depression) + no CVA residual symptoms + MMSE [21,25] (CI ss.) or MMSE [27,30] (matched NC ss.) that agreed to participate:
158 LASA ss. administered at T1: Memory Test Battery and additional MMSE
8 CI dropped out
Dementia assessment, 2 years later (T2): CAMDEX, GP medical records or MMSE > 26 (NC):
Nr. of ss. classified to CAMDEX ‘minimal dementia’ category:
6 min.dem. (T1) 10 min.dem. (T1);T2 ‘non-demented’
5 min.dem. (T2);T1 ‘non-demented’
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Footnotes
1 Tombaugh and McIntyre (1992) reported that the most frequently used cut-off value
for cognitive impairment is 23/24, but their review (Table 2) showed that cognitively
intact elderly subjects generally score higher than 24 – on average 28. Thus, LASA
participants with MMSE>26 are most likely not demented or in cognitive decline,
especially regarding their low average level of education. In addition, when the CI
range would be extended from 21-25 to 18-25, this might result in too many demented
subjects (or ‘mild cognitively impaired subjects’; Tombaugh & McIntyre).
2 A pilot study with elderly subjects (Molster & Koekkoek, 1997) showed that mirror-
reading words in lower-case letters was too difficult, because several lower-case
letters that are rotated on the vertical axis, produce other normal letters (e.g., “b” and
“d”). Using upper-case letters avoids this problem.
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