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DOI 10.1007/s00702-004-0159-2
J Neural Transm (2004) 111: 1141–1154

Aging and working memory: early deficits in EEG

activation of posterior cortical areas

P. Missonnier1;2;
, G. Gold3;
, U. Leonards1 , L. Costa-Fazio2;3 ,

J.-P. Michel3 , V. Ibáñez1 , and P. Giannakopoulos2;4
1
Neuroimaging Unit,
2
Service of Geriatric Psychiatry, Department of Psychiatry, and
3
Department of Geriatrics, University Hospitals of Geneva, Geneva, and
4
Department of Experimental Psychology, Service of Old Age Psychiatry,
University Hospitals of Lausanne, Prilly, Switzerland

Received April 1, 2004; accepted April 17, 2004

Published online June 21, 2004; # Springer-Verlag 2004

Summary. Using the n-back task, we recently identified, in young subjects, a

positive-negative event related potential component (PNwm) in a time-range
window between 140 and 280 ms after stimulus onset representing an electro-
physiological correlate of working memory load. To evaluate age-related elec-
trophysiological changes in working memory processing, we applied the same
neuropsychological paradigm and compared densities of the PNwm component
in 17 young (mean age: 26) and 17 healthy elderly individuals (mean age: 75).
Both age groups displayed a PNwm component during the two working memory
tasks. For the 1-back task, densities were similar in both young and elderly
individuals. In contrast, PNwm densities increased with higher memory load
(2-back>1-back) in the younger but not in the older group. This difference
was mainly observed over parietal electrodes suggesting an impaired activation
of neural generators within this brain region. The present results are consistent
with the hypothesis of decreased brain reserve in the elderly and provide evi-
dence for age-related deficits in the recruitment of posterior cortical neurons
with increasing working memory load.
Keywords: Aging, event-related potentials (ERPs), working memory.

Introduction
Working memory (WM) refers to processes involved in the short term main-
tenance and manipulation of incoming information that are required for the
performance of complex time-limited tasks such as learning, comprehension,

Both authors have contributed equally to this work

1142 P. Missonnier et al.

planning, reasoning and decision making. Working memory includes the en-
coding of incoming information through sensory processing and storage in
short-term buffers, continuous upgrade of these buffers, and the activation of
executive processes, such as on-line manipulation, inhibition, and response co-
ordination which operate on the contents of the short term buffers. In terms of
Baddeley’s working memory model (Baddeley, 1992, 1986), the first two stages
involve a modality-specific, limited short-term buffer or slave system, e.g. the
‘‘visuospatial sketchpad’’ located in primary and secondary visual cortices, and
the posterior parietal cortex. The third stage involves a ‘‘central executive’’ in
the prefrontal cortex, which is responsible for the allocation of processing
abilities into the ‘‘visuospatial sketchpad’’. In other models of working mem-
ory, the three processes can be distinguished into those that are automatic,
primarily driven by the external stimulus (‘‘bottom-up’’, pre-attentive process-
ing), and those that are under voluntary control (‘‘top-down’’, attention de-
manding) (e.g. Desimone et al., 1995; Tomita et al., 1999).
It is generally accepted that working memory performance declines with
age (Craik and Byrd, 1982; Craik and Jenning, 1992). Earlier studies showed
that elderly individuals have decreased limits in storage abilities indicating a
decline of bottom-up processing (Foos, 1989). Consistent with these observa-
tions, age-related activation changes during working memory processes were
described in the extra-striate cortex and temporal lobe (Cabeza et al., 1997;
Grady et al., 1998), suggesting impaired sensory information processing.
Deficits in executive control have also been described in the elderly (Craik,
1990; Morris et al., 1988), and recent functional imaging studies show that
decreased activation of the dorsolateral prefrontal cortex correlates well with
working memory deterioration in normal aging (Reuter-Lorenz et al., 2000;
Rypma and D’Esposito, 2000). However, storage in the short-term memory
buffer takes place following sensory input across several hundred milliseconds
(Cowan, 1984, 1995) and functional imaging studies cannot identify such early
cognitive processes. Electrophysiological studies, which can provide a high
temporal resolution, have thus been used to explore age-related modifications
of working memory processes in a variety of paradigms (Friedman, 1995, 2000;
McEvoy et al., 2001; Rugg et al., 1997) but have mostly focused on late event-
related potentials (ERPs; for review see Onofrj et al., 2001).
Although early contributions pointed to the presence of early ERP with a
poststimulus peak before 280 ms related to visual short-term memory (Begleiter
et al., 1993; Chapman et al., 1978), only one previous report focused on early
ERP responses during the successful performance of spatial and verbal n-back
working memory paradigms (Mc Evoy et al., 1998). Mc Evoy and colleagues
found an EP deflection occurring 250 ms after spatial stimulus in central areas
and proposed that this response may reflect an activity related to spatial working
memory update. However, these results are difficult to interpret in the absence of
a control task. Using an adapted version of the n-back working memory task, we
identified a significant Positive-Negative waveform (PNwm) component between
140 and 280 ms after stimulus onset by subtracting ERP waveforms of memory
tasks (1-back and 2-back) from memory-free control tasks (detection or 2-back
passive). The amplitude of the PNwm increased significantly with higher memory
 EEG activation of posterior cortical areas 1143

load (2-back>1-back). This PNwm component is superimposed on the standard

ERP P200 and N200 components and provokes shortening of their peak laten-
cies for the memory tasks compared to controls (2-back<1-back<control). As
shown by Independent Component Analysis, the PNwm consists of two indepen-
dent sources localized over parietal electrodes, both specific for the memory
tasks and absent for control tasks (Missonnier et al., 2003). We report here an
EEG activation study using the same neuropsychological paradigm in cogni-
tively intact young and elderly individuals and compare the patterns of the PNwm
component between the two age groups. Supporting the notion of decreased
brain reserve in the elderly, our data reveal for the first time to our knowledge
early age-related changes in the electrophysiological activation of posterior cor-
tical neurons when increased working memory load is present.

Subjects and methods

Participants
Thirty-four healthy right-handed (Oldfield, 1971) volunteers (aged 23–88 years) participated in
this study. There were 17 young adults (9 women, 8 men; mean age: 26.15  3.10 SD) and 17
elderly individuals (8 women, 9 men; mean age: 75.05  8.72 SD). All participants had normal or
corrected-to-normal visual acuity, and none reported a history of sustained head injury, or neu-
rological or psychiatric disorders. Moreover, none exhibited alcohol or drug abuse or the presence
of a severe physical impairment. Participants with regular use of psychotropics, stimulants and
b-blockers were excluded. The young adult group included undergraduate or graduate students
of the University of Geneva. Elderly participants, with a high school degree or equivalent,
were recruited through the University of Geneva and the Department of Geriatrics. All subjects
displayed normal performance on an extensive neuropsychological testing (Table 1). Informed
written consent was obtained from all participants and the study was approved by the local Ethics
Committee.

Experimental design
Subjects watched a continuous stream of letters (pseudo-random sequences of consonants and
vowels) common to the French alphabet on a computer screen and pressed a computer-controlled
pushbutton with the index finger of their right hand as soon as a target appeared (response trials).
For non-target trials, no motor response was required (no-response trials). Targets were defined
according to the n-back design (Fig. 1).
Stimuli consisted of white letters, type ‘‘Arial’’ (2  2.5 visual angle), with 10% grey noise,
embedded in a 50% random noise grey rectangular background patch (6  6.7 visual angle).
There was no change in the mean luminance when letters or background patches appeared.
Stimuli were presented for a duration of 0.5 sec, separated by 5 sec intervals (onset to onset)
during which a dot helped subjects maintain fixation.
Three different tasks were used: in a simple detection task (control), sequential letters or
background patches without letters were presented. Subjects responded as fast as possible when
background patches without letters appeared. In the 1-back task, the target was any letter identical
to the one immediately preceding it. In the 2-back task, the target was any letter that was identical
to the one presented two trials back. Thus, working memory load increased from control (mem-
ory free-condition) to 1-back (moderately demanding) and 2-back tasks (highly demanding).
Each task was tested in three stimulus sequences of 30 images each, adding up to 90 trials per
task. Before each sequence block, subjects were informed about the nature of the task, and several
warm-up trials were performed. A control task block was followed by one block of the 1-back
condition, three blocks of the 2-back condition, two blocks of the 1-back condition, and two
blocks of the control task. No feedback on performance was provided.
1144 P. Missonnier et al.

Table 1. Neuropsychological values (mean  standard deviation) in the present series of elderly
controls

Functions Tests Values

Global test Mini Mental State 28.80 (1.32)

(Folstein et al., 1975)
Executive function Verbal Fluency Test 23.25 (6.50)
(Borkowski et al., 1967)
Trail Making Test B (sec) 83.25 (38.19)
(Reitan, 1958)
Language abilities Boston Naming Test 19.86 (4.93)
(Kaplan et al., 1983)
Standardised praxis Transitive Ideomotor praxis 4.93 (0.26)
(Schnider et al., 1997)
Intransitive Ideomotor praxis 10.00 (0.00)
(Schnider et al., 1997)
Reflexive praxis (Poek, 1985) 3.87 (0.35)
Gnosis Ghent’s Overlapping 3.93 (0.26)
Figures Test (Ghent, 1956)
Attention WAIS-R; Code (Wechsler, 1981) 11.56 (2.22)
Trail Making Test A (sec) 50.76 (16.77)
(Reitan, 1958)
Memory tests Digit Span Forward 6.50 (2.74)
(Wechsler, 1955)
Corsi Block-Tapping test 5.33 (0.81)
(Milner, 1971)
French adaptation of the
Buschke Double Memory
Test (Van der Linden et al., 1999)
free recall total 31.00 (4.97)
induced recall total 15.50 (3.41)
recognition 16.00 (0.00)
deferred free recall 11.25 (0.96)
deferred induced recall 4.00 (1.36)
Shapes Test (Baddeley, 1994) 34.75 (2.50)

Electrophysiological recordings
Continuous electroencephalography (Micromed, Brain Quick system 98, Treviso, Italy) was
recorded, using twenty surface electrodes placed over the scalp according to the 10–20 interna-
tional electrode placement system (Homan et al., 1987). Linked earlobes were used as a refer-
ence. Skin impedance was kept below 5 k
. Physiological signals were sampled at 1024 Hz, the
lower cut-off was 0.33 Hz and the upper cut-off was 500 Hz. Right, left, supra- and infra-orbital
electrodes monitored horizontal and vertical electro-oculograms. TTL-pulses were used to syn-
chronise with stimulus onset, and off-line to segment the continuous electroencephalography data
into epochs. Reaction times and subjects’ performances were recorded.

Waveform analysis
Data were analysed with NeuroScan software (NeuroScan Inc, Herndon, VA, USA). After arte-
fact removal and off-line correction of ocular artefacts (threshold reduction algorithm), data from
trials with correct answers were averaged according to the task condition (control, 1-back,
 EEG activation of posterior cortical areas 1145

Fig. 1. A Schematic representation of the control task (first row) and the two working memory
tasks (second and third row). In the control task, the subject’s task was to press a pushbutton as
soon as a non-letter patch appeared. During 1-back and 2-back tasks, the subject was asked to
press the button only when the presented letter was identical to the one that had been shown one
trial back (1-back task) or two trials before (2-back task) in the sequence (response trials). Note
that both response and no-response trials require working memory. B Sequence timing: each
stimulus was presented for 0.5 sec, followed by a delay interval (4.5 sec) during which the
subject fixed a small point

2-back). All correct answers were combined (response to a target and no response in the absence
of a target) since working memory is required in both situations and since prior research has
shown that there is no difference between response and no response conditions on the studied
ERPs (Missonnier et al., 2003). Combined ERPs were then averaged over a window of 700 ms
with a 200 ms pre-stimulus onset and band-pass filtered between 0.33 Hz and 30 Hz, 24
dB=octave for low-pass filter. Peak latencies of the ERP components were measured from the
stimulus onset to the time of the peak maximum.
The visual P100 component latency was measured at the O1, Oz, and O2 electrode sites. The
maximal peak amplitudes of the N160 component were measured over frontal and central
electrode sites in both age groups. The N160 component was best distinguished from the
N100 at the C3, Cz, and C4 sites and these sites were thus selected for the N160 latency
measurements. For these two components, peak latencies were measured from the stimulus onset
to the time of the peak maximum, and the amplitudes were measured from the pre-stimulus
baseline to the peak maximum and then normalised through logarithmic transformation.
To isolate the PNwm component, we performed an ERP waveform subtraction analysis
between the n-back and the control tasks. Electrodes F3, Fz, F4, C3, Cz, C4, P3, Pz and P4
were selected for analysis in keeping with the antero-posterior distribution of the PNwm compo-
nent (Missonnier et al., 2003). The intersection of the positivity and negativity component with
baseline was the temporal limitation for the calculation of the density (area in mV2). Temporal
limits were not identical in both age groups and subjects. Densities of both the positivity and
negativity components were divided by the time range defined by the temporal limits in each
subject and condition to correct for this difference and then normalised through logarithmic
transformation.
Repeated measures ANOVA was used to compare reaction times (RT) and performances (%
of correct responses) between age groups and task conditions. Similar ANOVAs were used to
compare EEG-latency and densities among the different task conditions (control, 1-back and
1146 P. Missonnier et al.

Table 2. Mean reaction times (in milliseconds) and mean performances (in percent) with
standard errors (SE) for the control task, 1-back and 2-back tasks for young and elderly
subjects (n ¼ 17)

Tasks Reaction times Performances

Young subjects Elderly subjects Young subjects Elderly subjects

Control 662.68 (2.44) 854.35 (2.92)

99.88 (0.87) 99.47 (0.24) ns

1-back 712.42 (2.64) 917.00 (3.08)
99.35 (0.26) 99.11 (0.27) ns
2-back 802.22 (3.22) 1064.72 (3.47)
97.29 (0.39) 91.99 (0.51)


p < 0.001;

p< 0.0001; compared to young subjects. See text for details

2-back). The significance values were determined using the Greenhouse-Geisser correction. Two-
tailed differences of p< 0.05 were considered significant. The Scheffe test was used for post-hoc
analyses. Multivariate analysis of variance was performed to control for a potential interaction
between age and education in their effect on PNwm densities.

Results
Behavioural data
Averaged reaction times increased significantly with age (F(1, 32) ¼ 20.76,
p<0.0001) (Table 2). Young subjects responded faster than did elderly subjects
whether the performed task required working memory (1-back and 2-back) or not
(control). A significant task effect was also observed (F(2, 64) ¼ 41.30, p<0.0001)
as subjects responded the fastest in the control task and the slowest in the 2-back
task, independently of their age. There was no interaction between age and task.
Performance was related to task (F(2, 64) ¼ 61.19, p<0.0001). Although
performances for the control and 1-back tasks did not differ significantly, all
subjects performed significantly worse in the 2-back task (Scheffe p<0.001).
Subjects’ performances were also affected by age (F(1, 32) ¼ 13.94, p<0.001).
Post hoc analyses revealed that this effect was restricted to the 2-back task
(Scheffe p<0.001). There was a significant interaction between age and task
(F(2, 64) ¼ 15.69, p<0.0001) (Table 2).

ERP components
In Fig. 2, averaged waveform ERPs (for correct trials with and without required
motor-response combined) were plotted for each of the three tasks (control, 1-
back and 2-back) (Fig. 2A: young, Fig. 2B: elderly subjects). As expected, the
visual stimuli elicited a topographically distinct positive response over occipital
regions about 100 ms after stimulus onset (P100 component). This component
was observed for all three tasks (detection, 1-back and 2-back). Its latency and
amplitude were free from age-, electrode- or task-related effects. The N160

Fig. 2. Grand average waveforms, from a subset of 12 electrode sites, for the control task
(dashed lines), the 1-back (dotted lines) and 2-back (solid lines) tasks, averaged over response
and no-response trials for young (A) and elderly (B) subjects
EEG activation of posterior cortical areas 1147
1148 P. Missonnier et al.

component occurred 13 ms later in the older group (peak latency of 167 ms

versus 154 ms in the young group; F(1, 32) ¼ 14.96, p<0.001). There was no
task or electrodes-related effects. However, the N160 amplitude was free from
age-, electrode- or task-related effects.

The positive-negative working memory component

(PNwm component)
Figure 3 shows the PNwm component, obtained by subtracting ERP waveforms
for the control task from the 2-back (Fig. 3A) and 1-back tasks (Fig. 3B), in
young and elderly subjects. The PNwm component was delayed in the older

Fig. 3. Frontal (Fz), central (Cz) and parietal (Pz) grand average waveforms of the PNwm
component, representing ERP differences between 2-back task and control task and between
1-back task and control task respectively, for young (dashed lines) and elderly (solid lines)
subjects. For younger subjects, the temporal window on Cz electrode lasted from 120 to 228 ms
for the positivity and from 228 to 295 ms for the negativity of the 1-back PNwm component, and
from 123 to 220 ms for the positivity and 220 to 286 ms for the negativity of the 2-back PNwm
component. For elderly subjects, the positivity of the PNwm component provoked by the 1-back
task lasted from 166 to 247 ms and its negativity from 247 to 313 ms, whilst the positivity of the
PNwm component provoked by the 2-back task lasted from 164 to 244 ms and its negativity from
244 to 311 ms, response and no-response conditions averaged. The shaded area of the PNwm
component represents the temporal window for young subjects. Grand average waveforms of
the PNwm component, representing ERP differences between 2-back task and 1-back task.
Waveform ERP differences were observed in younger subjects only with a temporal window
for the positivity from 140 to 208 ms and for the negativity from 208 to 275 ms
Table 3. Normalized density values (in mV2) and standard deviations (SD) of the PNwm component, obtained by subtracting ERP waveforms for the
control task from the 1- and 2-back tasks

Electrodes 1-back minus control 2-back minus control

Positivity Negativity Positivity Negativity

Young Elderly Young Elderly Young Elderly Young Elderly

Fz 0.52 (0.27) 0.57 (0.30) 0.71 (0.26) 0.67 (0.32) 0.70 (0.24) 0.61 (0.21) 0.79 (0.32) 0.66 (0.18)
Cz 0.48 (0.26) 0.56 (0.26) 0.63 (0.30) 0.66 (0.25) 0.78 (0.21) 0.68 (0.21) 0.78 (0.36) 0.62 (0.36)
Pz 0.53 (0.30) 0.47 (0.31) 0.69 (0.32) 0.53 (0.27) 0.88 (0.22) 0.62 (0.17)

0.78 (0.31) 0.54 (0.13)


p < 0.001;

p< 0.0001; compared to young subjects
EEG activation of posterior cortical areas
1149
1150 P. Missonnier et al.

group by 11 ms for the 1-back and for the 2-back task. This delay was not
statistically different from the age-related delay observed for the N160
component.
Table 3 shows normalised density values of the PNwm component for the
two age groups. For the 1-back task subtracted from control task, positivity and
negativity densities were not significantly different between young and elderly
subjects. No electrode effects or two-way interactions between age and electro-
des were observed. For the 2-back task subtracted from control task, positivity
and negativity densities were significantly larger in young compared to elderly
subjects (F(2, 32) ¼ 5.14 and F(2, 32) ¼ 4.55, p<0.001, respectively). Further-
more, a significant interaction between age and electrode was observed for both
positivity (F(2, 256) ¼ 3.04; p<0.05) and negativity components (F(2,
256) ¼ 3.50, p<0.05), indicating that the age effect occurred mainly over P3,
Pz and P4 posterior electrode sites (Scheffe p<0.01; p<0.05 and p<0.01,
respectively). Multivariate ANOVA confirmed a significant effect of age
(Wilk’s Lambda 0.58, df 6, p<0.05) even after controlling for educational
level. The latter had no significant effect (Wilk’s Lambda 0.90, df 6, p ¼ 0.81).
Consistent with these data, when comparing the highly demanding 2-back
task to the easier 1-back condition, PNwm densities increased significantly in
younger individuals (F(2, 32) ¼ 21.35, p<0.0001) but not in the older group
(Fig. 3C).

Discussion
From a behavioral point of view, it is important to note that despite a lower
performance for the 2-back task compared to younger individuals, our group of
healthy elderly still performed remarkably well on both 1 and 2-back tasks
(with a success rate close to 92% for the latter) suggesting the presence of a
highly efficient working memory. Although reaction times were slower in the
older group, there was no interaction between age and task, indicating that the
observed age-related increase in reaction time was most probably not due to
slower working memory processing. We were however able to demonstrate
working memory-related electrophysiological changes in elderly subjects.
The present study reveals that the PNwm component, a previously described
electroencephalographic correlate of early storage and retrieval phases of work-
ing memory processing in young subjects, is also present in elderly individuals.
Prior research using Independent Component Analysis has shown that the
PNwm component consists of two distinct sources with a maximal activity dis-
tributed over parietal electrodes, both specific for the memory tasks and absent
for a control task. In addition, our previous report demonstrated that other
distinct processes such as the detection of rare letters in the detection task, or
the sensory repetition effect of the same letter in the n-back tasks cannot
account for the observed ERP differences since the PNwm component was also
present when a passive task, perceptually identical to the 2-back task but
requesting no response, was used (Missonnier et al., 2003).
There were two main differences between young and elderly individuals
which concern the latency and amplitude of the PNwm component. First, the
 EEG activation of posterior cortical areas 1151

latency of the PNwm component was significantly higher for the old group. This
PNwm delay cannot be attributed to an age-related slowing at the early stages of
visual processing since there was no significant difference between groups on
the P100 component latency (Kutas et al., 1994; Onofrj et al., 2001). However,
the PNwm delay is most likely related to the N160 component latency increase
in the elderly group since the delay we report for the PNwm component did not
exceed that measured for the N160. This component is thought to reflect late
visual sensory processing (Dutsman et al., 1993; Polich and Star, 1984) and its
latency is known to increase with age (Kolev et al., 2002; McEvoy et al., 2001).
Second and most importantly, although the amplitude of the PNwm component
increased in the most demanding working memory condition (i.e. 2-back task)
in younger individuals, this was clearly not the case in the elderly. Moreover,
since comparable amplitudes of the PNwm component for the 1-back task were
observed in both age groups, the most plausible explanation is that both
younger and older subjects recruit the same number of neural generators in
the 1-back task but that the latter may not be able to activate additional neuronal
populations in the 2-back task. Prior research implies that the PNwm component
is related to sources in posterior parietal areas (Missonnier et al., 2003).
Furthermore, the interaction analysis between age and electrode sites implied
that the age effect on PNwm densities was strongest over parietal electrodes
suggesting an impaired activation of neural generators within this brain region.
Recently, functional imaging and ERP studies showed an age-related decrease
in the responsiveness of parietal cortices during the successful performance of
verbal, visual and spatial working memory tasks with a parallel recruitment of
anterior frontal, cingulate and temporal cortices (Cabeza et al., 2002; Cabeza
and Nyberg, 2000; Della-Maggiore et al., 2000; Grossman et al., 2002; McEvoy
et al., 2001; Milham et al., 2002). These changes might reflect brain efforts to
counteract neurocognitive decline (compensation hypothesis) or an age-related
difficulty in recruiting specialized neural mechanisms (dedifferentiation
hypothesis). Using functional imaging, it has been recently shown that high-
but not low-performing elderly individuals may compensate for the age-related
neural decline of parietal areas during working memory tasks, through the
activation of distinct neurocognitive networks within prefrontal and limbic
areas (Cabeza et al., 2002). Our results provide additional support to the com-
pensation hypothesis since the decreased activation of posterior cortical areas in
the elderly (and the possible plastic reorganization of other cortical networks)
occurs during the successful performance of the highly demanding 2-back task
but not during the less demanding 1-back working memory task.
The present observations should also be interpreted in conjunction with the
recent theories regarding the depletion of brain reserve in the course of aging
(Tisserand et al., 2001). Although it is now well documented that neocortical
neurons are numerically preserved in normal brain aging (for review see
Morrison and Hof, 1997), recent evidences suggest that some of them may dis-
play a gradual decline in the capacity to respond to metabolic stress and return to
the resting state. The decrease of this functional reserve has been partly attributed
to an age-dependent impairment of mitochondrial function (Toescu, 2000). In
line with these findings, the present data indicate the presence of deficits of the
1152 P. Missonnier et al.

electrophysiological reserve in the parietal cortex usually activated during the

performance of highly demanding working memory tasks. These deficits which
were not symptomatically manifest may represent the first sign of dysfunction in
the circuits subserving working memory which does not prevent the successful
completion of the task (Pelosi and Blumhardt, 1999). Future studies in large
series combining ERP and functional imaging are needed to elucidate whether
these early neurophysiological deficits are accompanied by subtle metabolic
changes within the parietal cortex and investigate whether there is a restricted
subgroup of healthy elderly individuals with preserved functional reserve during
visual working memory activation.

Acknowledgements
The authors gratefully acknowledge Dr. M. Gex-Fabry Pun for statistical assistance. This research
was funded by the Swiss National Foundation for Scientific Research (grant 3100-59110.99).

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Authors’ address: Dr. G. Gold, Department of Geriatrics, University of Geneva Hospitals,

1226 Th^
onex–Geneva, Switzerland, e-mail: gabriel.gold@hcuge.ch

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