![A framework to explain the prion-like induction and spreading of Aβ aggregation. (A) Amyloidogenic proteins such as Aβ typically have β-strands (red and green parts) that interact and mediate the aggregation of Aβ into long and unbranched amyloid fibrils. Such Aβ aggregation starts with a slow nucleation phase that may go through a series of intermediate states until the initial segment of the amyloid fibril is formed. Monomers are then added to the ends of the initial amyloid seed by conformational conversion. With increasing length, the growing amyloid fibril will eventually break up (spontaneously or actively through cellular processes). Thus, amyloid formation becomes self-propagating through the generation, release and spread of new amyloid seeds. (B) The nucleation phase can be greatly shortened by the addition of exogenous seeds (modified from [7]).](https://www.researchgate.net/profile/Henk-Verloo/publication/346676557/figure/fig1/AS:966060039737344@1607338070167/A-framework-to-explain-the-prion-like-induction-and-spreading-of-Ab-aggregation-A_Q320.jpg)
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Special article | Published 23 November 2020 | doi:10.4414/smw.2020.20376
Cite this as: Swiss Med Wkly. 2020;150:w20376
Conference report: dementia research and care
and its impact in Switzerland
Leyhe Thomasa, Jucker Mathiasb, Nef Tobiasc, Sollberger Marcd, Riese Floriane, Haba-Rubio Joséf, Verloo Henkg, Lüthi
Regulah, Becker Stefaniei, Popp Juliusj
aUniversity of Basel, Geriatric Psychiatry, University Department of Geriatric Medicine Felix Platter, and Centre of Old Age Psychiatry, Psychiatric University
Hospital, Basel, Switzerland
bHertie Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
cARTORG Centre for Biomedical Engineering Research, University of Bern, Switzerland
dMemory Clinic, Geriatric Psychiatry, University Department of Geriatric Medicine Felix Platter, and Department of Neurology, University Hospital Basel,
Switzerland
eUniversity Hospital of Psychiatry Zurich, Department of Geriatric Psychiatry, Zurich, Switzerland
fCentre du Sommeil de Florimont and Centre for Investigation and Research on Sleep/CHUV, Lausanne, Switzerland
gService of Old Age Psychiatry, Lausanne University Hospital, Switzerland, and School of Health Sciences, Switzerland
hPsychiatric University Hospital, Basel, Switzerland
iAlzheimer Switzerland, Bern, Switzerland
jOld Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, and University of Zürich, Department of Geriatric Psychiatry, University Hos-
pital of Zürich, Switzerland
Summary
In October 2019, a Swiss panel of experts met for the De-
mentia Summit in Brunnen, Switzerland, to discuss the lat-
est scientific findings on basic and clinical research, as
well as practical and political approaches to the challenges
of dementia disorders in Switzerland. Here, we present the
conference summary.
To study pathophysiological changes, as well as the un-
derlying mechanism of fluid biomarker changes, excellent
experimental approaches, including transgenic mouse
models, are available. Current knowledge about presymp-
tomatic disease progression is largely derived from the
longitudinal study of individuals with autosomal dominant
mutations (Dominantly Inherited Alzheimer Network).
Importantly, more than one third of identified dementia risk
factors can be modified. For example, sleep disturbances
are not only associated with dementia and neurodegener-
ation in specific brain regions, but also precede cognitive
decline and contribute to the development of brain pathol-
ogy.
Regarding the neuropsychological examination of demen-
tia disorders, standardised tests of social cognition, one of
the six cognitive domains that must be assessed accord-
ing to the fifth edition of the Diagnostic and Statistical Man-
ual for Mental Disorders, are missing, but now under de-
velopment.
The most important new therapeutic approach in the treat-
ment of Alzheimer’s disease is the current attempt to pre-
vent β-amyloid accumulation. While until now clinical stud-
ies have failed because of side effects or insufficient
clinical effectiveness, Biogen recently announced positive
results of high doses of aducanumab, a monoclonal an-
tibody against β-amyloid. Other approaches also show
promise. In China, sodium oligomannate has been ap-
proved to treat Alzheimer's disease. The substance sup-
presses gut bacterial amino acids-shaped neuroinflamma-
tion to inhibit Alzheimer’s disease progression.
Assistive technologies for dementia patients can help
identify relevant information for care and nursing, as well
as measurements for clinical interventions.
Dementia patients have a high risk of developing delirium,
even in the home environment. Therefore, it is necessary
to use and further develop multi-disciplinary and system-
atic detection and prevention strategies.
Homecare models for dementia patients with multidisci-
plinary teams have been established and evaluated and
should be expanded.
Dementia is the third-leading cause of death in Switzer-
land. In palliative care for severe dementia, the improve-
ment of quality of life is of primary importance.
The goals of the National Dementia Strategy, to increase
the quality of life in those affected and to reduce taboos
surrounding the disease, are still unrealised. The need for
further national and regional engagement in order to im-
plement the different findings of the strategy has largely
been acknowledged, and these implementations have be-
come the core tasks of a national dementia platform.
Keywords: dementia,Switzerland,transgenic mouse
models,Dominantly Inherited Alzheimer Network,sleep
disorders,social cognition,treatment studies,assistive
technologies,delirium,homecare models,palliative care,
National Dementia Strategy
Correspondence:
Prof. Thomas Leyhe, MD,
University of Basel,Geri-
atric Psychiatry,University
Department of Geriatric
Medicine Felix Platter,and
Center of Old Age Psychia-
try, Psychiatric University
Hospital,CH-4002 Basel,
thomas.leyhe[at]felixplat-
ter.ch
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Page 1 of 12
Introduction
Cognitive impairment and dementia constitute a growing
public health concern, with severe consequences for pa-
tients and their relatives, as well as for healthcare systems
and societies worldwide. Despite intensive research efforts
and major recent progress, the causes and mechanisms in-
volved in cognitive impairment and in dementias such as
Alzheimer’s disease (AD) are only partially understood
[1].
The increase in chronic, non-communicable diseases such
as dementia disorders is also one of the central challenges
for the Swiss healthcare system. Dementia diseases are
one of the most common diseases in old age, are consid-
ered the most common reason for long-term care of old-
er people, and are the third most common cause of death
in people above the age of 85 after cardiovascular diseases
and cancer [2]. Around the world, one person is diagnosed
with dementia every three seconds [3], and in Switzerland
there are around 29,500 new diagnoses a year. Alzheimer's
Switzerland estimates that around 155,000 people with de-
mentia live in Switzerland, of whom around 7400 are un-
der the age of 65 [4].
Since old age is the greatest risk factor for dementia, the
number of cases is expected to continue to rise, despite
the declining rate of new cases, due to increasing life ex-
pectancy and good medical care. No curative therapies are
available to date, and the failures of pharmacological re-
search so far leave only modest hopes for a corresponding
drug.
Facing this situation in October 2019, a Swiss panel of ex-
perts met for the Dementia Summit in Brunnen, Switzer-
land, to discuss the latest scientific findings from basic
and clinical research, as well as practical and political
approaches to the challenges of dementia disorders in
Switzerland.
Translational research (Mathias Jucker)
Although animals do not develop the typical symptoms
of dementia, transgenic mouse models are excellent mod-
els for studying pathophysiological disease mechanisms
and have proven their usefulness for biomarker research in
neurodegenerative diseases.
It has been shown that the intracerebral injection of β-amy-
loid-containing brain extracts can induce cerebral β-amy-
loidosis and associated pathologies in susceptible β-amy-
loid precursor protein (APP) transgenic mice. The same is
true when the injections are intraperitoneal, albeit the in-
duction occurs only after prolonged incubation times [5].
These and other experiments suggest that the induction and
spreading of β-amyloid (Aβ) aggregation in the brain fol-
lows a prion-like mechanism [6,7] (fig. 1).
Fluid biomarker research in mice started with the seminal
publication of Maia et al. [8]. Aβ and Tau in the cere-
brospinal fluid (CSF) of two well-characterised APP trans-
genic mouse models were measured. Both mouse models
exhibited Aβ deposition in the brain, but with different on-
set and progression trajectories. An age-related decrease
in Aβ42 peptide in mouse CSF of 50–80% and a smaller
decrease in Aβ40 were found, both inversely correlated
with the brain Aβ load. Strikingly, the same mice showed a
threefold increase in total endogenous murine Tau in CSF
at stages when Aβ pathology was prominent. This obser-
vation suggested for the first time that the increase of Tau
in the CSF in AD is caused by the Aβ deposition and not
by neurofibrillary tangles, since tangles do not occur in
APP transgenic mice [8]. In another study, robust increas-
es in neurofilament light chain (NfL) in CSF and blood in
murine models of alpha-synucleinopathies, tauopathy and
β-amyloidosis were reported [9]. Blood and CSF NfL lev-
els were strongly correlated, and NfL increases coincided
with the onset and progression of the corresponding pro-
teopathic lesions in the brain. Experimental induction of
alpha-synuclein lesions increased CSF and blood NfL lev-
els, while blocking Aβ lesions attenuated the NfL increase.
NfL increases were also found consistently in the CSF
and blood of human patients with α-synucleinopathies,
tauopathies and AD [9]. Thus, NfL appears to be a promis-
ing readout for Aβ- (and other proteopathic lesion)-target-
ing clinical trials.
The Dominantly Inherited Alzheimer Network (DIAN)
study focuses on the preclinical stages of AD. In this study,
individuals with autosomal dominant AD mutations are
observed longitudinally. It was found that the first changes
in the brain occur at least 10–20 years before dementia
symptoms appear [10]. Using an ultrasensitive immunoas-
say technology, it was found that NfL levels in the CSF and
Figure 1: A framework to explain the prion-like induction and spreading of Aβ aggregation. (A) Amyloidogenic proteins such as Aβ typi-
cally have β-strands (red and green parts) that interact and mediate the aggregation of Aβ into long and unbranched amyloid fibrils. Such Aβ
aggregation starts with a slow nucleation phase that may go through a series of intermediate states until the initial segment of the amyloid fibril
is formed. Monomers are then added to the ends of the initial amyloid seed by conformational conversion. With increasing length, the growing
amyloid fibril will eventually break up (spontaneously or actively through cellular processes). Thus, amyloid formation becomes self-propagat-
ing through the generation, release and spread of new amyloid seeds.(B) The nucleation phase can be greatly shortened by the addition of
exogenous seeds (modified from [7]).
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Page 2 of 12
serum are correlated with each other and are already ele-
vated at presymptomatic stages in DIAN participants. Lon-
gitudinal, within-person analysis of serum NfL confirmed
this elevation and revealed that the rate of change of NfL
was even more sensitive and could discriminate AD muta-
tion carriers from non-mutation carriers (on a group level)
almost a decade earlier than cross-sectional absolute NfL
levels (that is, 16.2 vs 6.8 years before the estimated symp-
tom onset). Serum NfL rate of change peaked in partic-
ipants converting from the presymptomatic to the symp-
tomatic stage and was associated with cortical thinning
(assessed by magnetic resonance imaging), but less so with
Aβ deposition or glucose metabolism (assessed by positron
emission tomography). Serum NfL was predictive for both
the rate of cortical thinning and cognitive changes as as-
sessed by the Mini-Mental State Examination and the Log-
ical Memory test. It was concluded that NfL dynamics in
serum predict disease progression and brain neurodegener-
ation even at early presymptomatic stages of familial AD,
which supports its potential as a clinically useful AD bio-
marker [11].
Sleep and cognition (José Haba-Rubio)
One third of the risk factors for dementia, such as hearing
loss, hypertension, social isolation and depression, can be
influenced [12].
Sleep is an indispensable biological function thought to
be essential for brain restoration and memory consolida-
tion [13]. As life progresses, there are significant changes
in sleep quantity and architecture, and there is also an
increased susceptibility to sleep disorders. Sleep distur-
bances are particularly frequent in subjects with cognitive
deficits such as mild cognitive impairment and dementia
[14].
These sleep disturbances have often been dismissed as
consequences of the disease process, reflecting the degen-
eration of the neural pathways that regulate sleep-wake
patterns and sleep architecture, or as consequences of its
related somatic and psychiatric co-morbidities. Neverthe-
less, accumulating evidence suggests that sleep distur-
bances occur very early in the cognitive decline process,
and different studies have shown that sleep duration, sleep
fragmentation and sleep pathologies can play a role in the
pathogenic process leading to cognitive impairment.
In a recent study, the subjective (evaluated using question-
naires) and objective characteristics of sleep (measured by
polysomnography) of 580 elderly participants (>65 years)
of the population-based CoLaus/PsyCoLaus study (Lau-
sanne, Switzerland) were compared between those with
cognitive impairment (measured by the Clinical Dementia
Rating Scale score), and those with normal cognition.
Sleep-disordered breathing (SDB) was more severe in par-
ticipants with cognitive impairment, and after adjustments
for confounding variables, the apnea/hypopnea index and
the oxygen desaturation index were independently associ-
ated with cognitive impairment [15] (table 1).
In addition, by analysing data from this large-scale cohort
from the general population, the association between
markers of sleep-related hypoxemia and brain anatomy in
775 participants who underwent full polysomnography and
brain magnetic resonance imaging were investigated. It
was found that a lower mean SaO2was correlated with
reduced volumes in the hippocampus-amygdala complex,
thalamus, basal ganglia and frontoparietal cortex, suggest-
ing a vulnerability of these regions to nocturnal hypoxemia
that might provide a possible explanation for SDB-associ-
ated neuropsychological deficits [16].
Finally, available but still limited data also suggest that the
treatment of sleep disorders, and particularly the treatment
of SDB, is associated with slower cognitive decline in pa-
tients with dementia [17].
In summary, sleep plays an important role in cognitive
processes and subjects with cognitive impairment have
more disturbed sleep. SDB, and in particular nocturnal hy-
poxemia, is associated with the presence of cognitive im-
pairment and a decrease in the volume of the hippocampus
and the amygdala. Prospective and interventional studies
are needed to determine the impact of treatment of sleep
Table 1: Association of polysomnographic variables with a Clinical Dementia Rating Scale > 0, multivariate analysis.
Odds ratio*95% confidence interval p value
Total sleep time, min 1.00 0.97–1.02 0.884
Stage N1, min 1.04 0.97–1.10 0.246
Stage N2, min 0.99 0.96–1.02 0.576
Slow wave sleep (stage N3), min 1.01 0.95–1.07 0.792
REM sleep, min 0.98 0.92–1.04 0.548
Sleep onset latency, min 0.97 0.91–1.04 0.466
Sleep efficiency, % 0.97 0.82–1.13 0.675
Wake after sleep onset, min 1.00 0.97–1.03 0.832
REM latency, min 0.99 0.96–1.01 0.309
Number of stage shifts 1.01 0.97–1.04 0.720
Apnoea/hypopnoea index, n/h 1.15 1.00–1.31 0.043
Mean SaO2, % 0.73 0.22–2.38 0.602
Lowest SaO2, % 0.79 0.56–1.12 0.184
Oxygen desaturation index ≥3%, n/h 1.09 0.96–1.22 0.173
Oxygen desaturation index ≥4%, n/h 1.17 1.01–1.36 0.033
Oxygen desaturation index ≥6%, n/h 1.33 1.03–1.72 0.029
Arousal index, n/h 1.00 0.86–1.16 0.993
PLMS index, n/h 1.00 0.95–1.06 0.885
REM = rapid eye movement sleep; AHI = apnoea/hypopnoea index; PLMS = periodic leg movements during sleep [15]. * Odds ratio for an increase of 10 units. Multivariate logistic
regression model adjusted for each variable (age, gender, hypertension, diabetes, metabolic syndrome, depression, lifetime depression, body mass index, alcohol and tobacco
consumption, drugs influencing sleep and level of education).
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Page 3 of 12
disorders such as apnoea syndrome on cognitive impair-
ment.
Assessment of social cognitive dysfunction –
the development of the Basel version of the
Awareness of Social Inference Test (BASIT)
(Marc Sollberger)
Social cognition is about cognitive and emotional process-
es ranging from emotion recognition, the ability to infer
other people’s thoughts and feelings, through to planning
socially adequate actions [18,19]. Consequently, social
cognitive functions are essential for our quality of life [20,
21].
According to the fifth edition of the Diagnostic and Sta-
tistical Manual for Mental Disorders (DSM-5), social cog-
nition is one of the six cognitive domains that must be
assessed for the diagnosis of a neurocognitive disorder.
However, in contrast to the other cognitive domains, such
as memory or language, tests that assess social cognitive
functions reliably and in an ecologically valid manner
within a reasonable timeframe are scarce [22]. Since social
cognitive deficits are observed to some degree in most
brain disorders, including neurodevelopmental, neurovas-
cular, neuroinflammatory, neurodegenerative and psychi-
atric disorders [19,22], the development of tests for use in
clinical populations is highly important.
According to a recent review article and a further literature
review on the clinical assessment of social cognition in
clinical populations [22,23], “The Awareness of Social In-
ference Test (TASIT)” [24] is probably one of the most
comprehensive instruments to date. TASIT comprises
video vignettes of actors depicting emotional and social
signals in a realistic manner. It has been shown to be valid
and reliable [25], displaying deficits in social perception in
patients with different brain disorders [26]. However, TA-
SIT is limited by several factors such as (i) the high so-
cio-emotional intensities portrayed by the actors, reducing
its sensitivity in detecting social cognitive deficits, (ii) the
long administration time, preventing its utility in clinical
routine, (iii) quite simple paradigms (only forced-choice
labeling tasks), which limit its accuracy in assessing social
cognitive functions, and (iv) the limited quality and con-
sistency of the film clips [10,11]. To overcome these lim-
itations, we adapted several parts of the test and renamed
it the “Basel version of the Awareness of Social Inference
Test (BASIT)” [27,28].
In collaboration with the film institute East End Film, 99
film clips showing basic emotions (i.e., anger, fear, disgust,
happiness, sadness and surprise) and social (i.e., cognitive
and affective perspective-taking) signals were shot with
eight professional, German-speaking actors. Importantly,
the actors were required to portray these emotions and
forms of communication at low, medium and high inten-
sities, i.e., three different socio-emotional intensities were
generated per scene [27,28]. These scenes were shown to
240 cognitively and psychically healthy people between 35
and 92 years of age. Each person watched each scene at on-
ly one given intensity (for example, participant 1 watched
scene 1 at low intensity, scene 2 at medium intensity, and
so forth, whereas participant 2 watched scene 1 at high in-
tensity, scene 2 at low intensity, and so forth). Figure 2
shows a screenshot of an example scene (in which anger at
low intensity is portrayed). The video clip of this scene can
be found online at Vimeo.com. By running Rasch models,
graphs that allowed scenes of different levels of difficul-
ty to be selected for use in clinical populations were pro-
duced.
The next step will be the administration of these selected
scenes to patients with neurodegenerative and psychiatric
disorders to examine their validity and reliability in com-
parison to other, less ecologically valid tests of social cog-
nition [22].
Figure 2: Screenshot of a scene in which anger at low intensity is portrayed. The video clip of this scene can be found online at Vimeo.com.
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Drug treatment of Alzheimer’s disease: state of
the art and new approaches (Thomas Leyhe)
Four drugs are currently approved to delay progression
in AD. These are the three acetylcholinesterase inhibitors
donepezil, galantamine and rivastigmine, as well as the
N-methyl-d-aspartate antagonist memantine. Furthermore,
there is also evidence for the effectiveness of Ginkgo Bilo-
ba EGb761 on cognition and non-psychotic behavioural
symptoms in patients with mild to moderate Alzheimer’s
dementia, so treatment with this preparation can also be
considered [29]. The approved drugs are all symptomati-
cally effective. They can delay the course of the disease,
but they cannot stop the neurodegenerative process. There-
fore, other active substances are urgently needed.
The most important new therapeutic approach in the treat-
ment of AD is the current attempt to prevent Aβ accumula-
tion. Aβ peptides arise from APP. APP can be broken down
by an alpha and a gamma secretase into end products that
do not form amyloid plaques. But it can also be broken
down by the enzyme β-site-APP-cleaving enzyme 1
(BACE-1), a β-secretase and the γ-secretase into amyloid-
forming Aβ peptides. Usually, the first route is preferred.
A shift towards the second route of degradation is con-
sidered the initial factor in AD. The resulting oligomers
and intermediate amyloid proteins are particularly toxic to
synapses. Finally, they aggregate spontaneously and form
the sparingly soluble, neurotoxic amyloid plaques [30].
The most important therapeutic approach is Aβ immunisa-
tion. Several large phase III studies of passive immunisa-
tion against Aβ have been completed in patients with mild
to moderate AD. The active ingredient bapineuzumab has
been shown to cause a reduction in the amyloid loading
of the brain in patients with Alzheimer's dementia in vivo.
This was demonstrated by positron emission tomography
using Pittsburgh Compound B ([11C] PiB-PET), a mark-
er of cortical fibrillar Aβ [31]. But neither bapineuzumab
[32], solanezumab [33], crenezumab [34] nor gantenerum-
ab [35] showed an effect on the primary endpoints cogni-
tion and everyday function.
Another antibody, aducanumab, on the other hand, was not
only shown, in a Phase Ib study, to reduce dose-depen-
dent amyloid peptides in the brains of patients with mild
Alzheimer's dementia, but also to delay cognitive decline
[36]. Aducanumab is a monoclonal antibody (mAb) that
binds soluble and insoluble Aβ in the brain and leads to a
significant reduction of the neurotoxic peptides. In spring
2019, two Phase III studies of aducanumab (EMERGE
and ENGAGE) were stopped after a futility analysis [37].
However, after a reanalysis of its data, the EMERGE study
has now shown that the group who received a higher dose
(10 mg / kg body weight) of the mAb actually saw an im-
provement in cognitive function. The effect was not signif-
icant at lower doses. Furthermore, a reanalysis of the data
from the ENGAGE study showed that the patients in this
study who received at least 10 doses of 10 mg / kg mAb
also showed a significant improvement in cognitive func-
tion. With good safety data, the decision of the US Food
and Drug Administration (FDA) on whether aducanumab
will receive approval for the treatment of AD is now eager-
ly awaited [38].
Phase III clinical trials of the mABs gantenerumab and
BAN2401 have been launched in AD patients, with results
expected in 2022 or 2023. The mAb programmes consider
increasing doses and targeting oligomers a potentially ap-
propriate strategy [39].
A further challenge for these therapies is that the patholog-
ical processes begin 10–15 years before the onset of symp-
toms. In at risk groups, such as patients with autosomal
dominant AD, who develop symptoms between the ages
of 30 and 50 years, mAbs (solanezumab, gantenerumab)
have been used 15 years before the onset of the disease
(DIAN-TU; ClinicalTrials.gov: NCT01760005). Howev-
er, a top-line analysis of the first phase II/III clinical trial
performed by the DIAN-TU trials platform showed that
both of the investigated drugs missed the primary end-
point. That endpoint was a statistically significant differ-
ence between drug and placebo on the DIAN Multivariate
Cognitive Endpoint, a composite of four cognitive tests de-
veloped by DIAN for this stage and type of AD. Additional
analyses are ongoing. Given the small sample size and the
heterogeneity of disease stage in this trial, some of those
analyses will focus on individual trajectories [40].
Another at-risk group is asymptomatic persons who have
shown signs of amyloid pathology during screening. The
use of solanezumab is being investigated in this group
(ClinicalTrials.gov: NCT02008357) and the results are still
pending. Unfortunately, another study with a substance
that should prevent plaque formation by inhibiting the en-
zyme BACE-1 in a similar group has even led to a de-
terioration in cognitive abilities [41]. Other studies with
substances targeting BACE-1 or the γ-secretase were also
stopped because of ineffectiveness or side effects [42].
Other interventions currently in clinical trials target the
tau-related neurological damage. The majority of the sub-
stances being investigated are disease-modifying agents
[43].
In China, sodium oligomannate has been approved to treat
AD. The substance therapeutically remodels gut microbio-
ta and suppresses gut bacterial amino acids-shaped neu-
roinflammation to inhibit AD progression [44].
The future of Alzheimer’s treatment might be a multi-drug,
multi-modal approach akin to chemotherapy. How to com-
bine potential drug treatments, how to select the appropri-
ate subgroups, and in what order they should be selected
are all still undecided. The current trends clearly suggest
that segmentation and non-amyloid directed methods will
fundamentally alter the therapeutic landscape.
Assistive technologies for dementia patients –
current state of the art and perspectives (To-
bias Nef)
Patients with cognitive impairment often have a strong de-
sire to live at home independently. Given the degenera-
tive nature of the disease, most patients will experience a
moment when living independently becomes impossible.
Finding the appropriate moment to move to an institutional
care setting is a trade-off between the patient’s desire to
stay “at home” and the potential risks associated with liv-
ing independently with impaired cognition (e.g., safety, ac-
tivities of daily living). In this situation, sensor technolo-
gy can help supervise the patient’s activities and can share
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this information with formal and informal caregivers. The
basic assumption is that if the caregivers know about the
patient’s whereabouts and activities (e.g., cooking, eating,
sleeping), this will help them to optimise formal and infor-
mal caregiving, allow interventions in emergencies (e.g.,
falls), and postpone the moment when institutional care is
needed (fig. 3).
Wearable sensors, ambient sensors or a combination of the
two can monitor activities in the patient's home. Wearable
sensors (e.g., a smartwatch) can measure body movements,
recognise activities and measure physiological parameters
(e.g., respiration, heartbeat). This sensor type requires the
patients’ cooperation and also particular actions (e.g.,
charging and wearing the sensor). Therefore, this sensor
type is not optimally suited to patients with cognitive im-
pairments. Patients often forget to wear the sensor or to
recharge the device [45]. This problem can be solved with
an ambient sensor system that consists of six to ten match-
box-sized sensor boxes that are distributed throughout the
patient's home. The system uses cheap, battery-powered,
passive, infrared-based motion recognition sensors that
communicate wirelessly and are easy to install in the pa-
tient's home. State-of-the-art machine learning algorithms
can recognise patients' activities with a sensitivity and
specificity both above 90% [46]. Typical information that
can be extracted from the sensors are daily sleeping pat-
terns, cooking, eating, and some emergency situations
(e.g., falls) [47]. It was shown that these sensors are well
accepted by patients and caregivers and that they work reli-
ably in different apartments [48]. Further studies are need-
ed to investigate whether the use of such sensors also fos-
ters independent living and allows institutional care to be
delayed.
Another topic discussed in the meeting was the use of com-
puter gaming technology to diagnose cognitive impair-
ments. Previous work has shown that specifically designed
computer games are fun to play for patients with cognitive
impairments [49,50]. These games must automatically ad-
just their difficulty levels to the abilities of the patients to
prevent frustration occurring because the game is too diffi-
cult or too easy. Depending on the task in the game, differ-
ent cognitive abilities can be analysed (e.g., memory, se-
lective attention, processing speed). Today, it is clear that
computer games can be an easy-to-use and fun addition
to a traditional cognitive assessment in the memory clinic
[51], but it remains unclear how to link the multiple perfor-
mance measures in a game to individual cognitive abilities.
Also, it is not known how relevant the abilities tested in the
games are to daily life.
Prevention of delirium at home: public health
issues and avenues for improvement (Henk
Verloo)
Switzerland’s public healthcare system is under significant
pressure to maintain home-dwelling older adults (HDOAs)
in their abodes for as long as possible. Indeed, the majority
of HDOAs want to do exactly that, even when they need
substantial health care and support [52]. This public
healthcare policy approach means that hospitalised older
inpatients are quickly discharged home, with their follow-
up care being managed by home healthcare services [53].
Their fragile condition, however, puts them at high risk of
developing delirium, a disorder linked to high morbidity,
poly-medication and high mortality [54] (table 2).
Delirium is a neuropsychiatric syndrome defined by a dis-
order of attention or consciousness, accompanied by a
worsening of cognitive, perceptive and behavioural func-
tioning. Delirium usually appears acutely, within a few
hours or days, and its clinical features fluctuate during the
day [55,56]. Delirium can be characterised by motor sub-
type, namely as hypoactive, hyperactive or mixed delir-
Figure 3: Ambient (contactless), wearable and object-attached sensors measure the behaviour of a patient at home or in the hospital. Ma-
chine learning algorithms recognize the patient’s activities and the multimodal patient model combines this information with physiological para-
meters to produce care-relevant information and/or trigger patient-specific interventions targeting cognitive function, perception, motor function
or other symptoms.
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Page 6 of 12
ium [57]. Understanding of the prognosis of delirium is
still evolving, with a growing body of literature exploring
associations between the classification of delirium’s aeti-
ologies, its motor subtypes, and the severities of its out-
comes [58,59]. Several authors have documented that the
prevalence of delirium among hospitalised older inpatients
can reach 60% [60]. Also, the non-detection of an episode
is estimated to occur in approximately half of older pa-
tients leaving hospital [61]. Better consideration of the
high prevalence of post-hospitalisation confusion, its non-
detection, and the under-management of silent episodes of
delirium may help to reduce the disorder’s negative im-
pacts on the older patients themselves, as well as their in-
formal and formal caregivers [62].
Despite a substantial body of knowledge transfer and evi-
dence-based guidelines, the detection of delirium remains
problematic in all healthcare settings [63]. Delirium is
common during emergency department (ED) stay and is
particularly prevalent among older adults. As many as
7–17% of older adults presenting at the ED meet the di-
agnostic criteria for delirium. ED professionals frequently
miss delirium, perhaps in up to 80% of cases. ED delirium
is associated with significantly increased in-hospital,
30-day and 6-month mortality, as well as the loss of inde-
pendence, accelerated cognitive decline and post-traumatic
stress disorder, all of which are troubling to both patients
and their families [64].
Strategies for the prevention or early detection of delirium
at home are scarce, and their efficiencies hardly investi-
gated. The evidence accumulated in hospitals and the rare
clinical studies of interventions for the prevention of phys-
ical decline among HDOAs could together serve as the
foundation for developing targeted interventions for early
detection and treatment [65]. New avenues involving the
use of new technologies for the early detection of deliri-
um should be explored [66]. Interventions should also in-
clude educational components, supported by well-estab-
lished clinical pathways at hospital or ED discharge, so
that the healthcare professionals involved can quickly de-
tect signs of deterioration among HDOAs and contribute
to the development, application and evaluation of effective
prevention strategies for older adults who still live at home.
There is an urgent need to develop new knowledge to help
prevent delirium at home. A rigorous evaluation of inter-
ventions must be carried out, investigating both their ef-
fectiveness at improving HDOAs' well-being and their ef-
ficiency in terms of healthcare spending.
Assertive community treatment for the elderly
in the canton of Thurgau (Regula Lüthi)
The project “assertive community treatment for the elder-
ly” began as a one-nurse project, born out of necessity. The
psychiatric clinic of Münsterlingen noted that too many
older people discharged from inpatient treatment returned
to the ward too soon, as their integration back at home was
not successful. Exhausted relatives, not enough knowledge
about disease management and overwhelmed friends were
some reasons. Another was the lack of expertise in psy-
chiatric disorders within domestic care teams at this time
(2010).
The newly implemented treatment was successful. Howev-
er, as costs for outpatient treatment are not covered by the
regular health insurance, financial support was supplied by
the canton of Thurgau, and for the first three years it had
the status of a “pilot project”. After this successful period,
it was integrated into routine care – still needing financing
from the canton.
The two types of outpatient treatment are transitional treat-
ment and long-term treatment. The transitional treatment
is especially helpful for the elderly as it is for a limited
time of three months only, but consists of an extensive case
management. The treatment is a personalised intervention
tailored to the specific needs of patients and their rela-
tives. Mental health nurses, social workers, psychiatrists
and psychologists form an interdisciplinary team with a fo-
cused psychiatric knowledge base.
Assertive community treatment is nowadays a respected
and evidence-based intervention. Several guidelines con-
firm its impacts on mental health and quality of life [67,
68]. But the costs of this treatment are a problem all over
Switzerland. There now exists a new task force at the Uni-
versity of Applied Science SUPSI charged with collecting
data about the diverse funding methods and then proposing
a new form of financing to all the cantons of Switzerland
and to the health insurance companies.
Back to the assertive community treatment for the elderly
in the canton of Thurgau: one of the robust results of this
new outpatient treatment was a significant reduction in the
number of days patients spent in the psychiatric hospitals
(fig. 4).
Another, qualitative outcome was the easing of the burden
on the patients’ relatives. The third outcome was a training
programme about psychiatric disorders, recovery orienta-
tion, etc. for all nurses working in primary care teams. It is
an ongoing and successful treatment, and therefore a small
but important improvement in the integrated mental health-
care system.
The end of life with dementia (Florian Riese)
Dementia is a potentially life-limiting condition that leads
to unique palliative care needs (fig. 5).
After cardiovascular disease and cancer, dementia has be-
come the third most frequent cause of death in Switzerland,
Table 2: Population-based sample (n = 36,792) of elderly persons (65+) returning home from a multisite Swiss public teaching hospital between 2015 and 2017 (based on the
principal diagnostic ICD-10 categories F050, F051, F058 and F059).
ICD-10 Description Frequency
F050 Delirium not superimposed on dementia 14
F051 Delirium superimposed on dementia 619
F058 Other form of delirium 324
F059 Delirium, without precision 78
Total 1035
Source: Verloo, unpublished data 2019
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Page 7 of 12
accounting for almost 10% of all deaths in 2017 [2]. People
who die from dementia as an underlying condition mostly
die from dehydration, cachexia and infections as immedi-
ate causes [70]. Many more die not from dementia, but
with dementia, i.e., while suffering from varying degrees
of dementia as a comorbidity. International data suggest
that most people with dementia – at least in the advanced
stages – die either in hospital or in long-term care [71].
Even though dementia is often (mis-)understood as mainly
a cognitive or behavioural condition, there is no indication
that physical symptom burden is lower at the end of life
in patients with dementia than in those without [72]. The
behavioural and psychological symptoms of dementia
(BPSD) often complicate end-of-life care. Agitation re-
mains frequent, even in the final months before death [73],
but more longitudinal studies are needed to elucidate the
course of BPSD in advanced dementia [74]. Treatment
of BPSD is best achieved by adopting a systematic ap-
proach and frequently involves both non-pharmacological
and pharmacological measures [75].
In its advanced stages, dementia is frequently associated
with reduced intake of food and liquids, as well as with
an increased risk of infections, particularly pneumonia.
Therefore, the potential use of tube feeding, artificial hy-
dration and antibiotics in (repeated) episodes of pneumonia
are key questions in dementia care. Based on the available
evidence, the current guidelines of the Swiss Academy of
Medical Sciences advise against the use of percutaneous
endoscopic gastroscopy feeding tubes in advanced demen-
tia [76]. The available evidence for the use of artificial
Figure 4: Development of inpatient days for 68 patients receiving transitional assertive community treatment in 2010. This diagram shows a
significant reduction in inpatient days for the 68 patients who received the transitional assertive community treatment (Reference source: Pre-
sentation Psychiatry Planning – New Nursing Elements in the Provision of Psychiatric Services GDK, Bern 2011).
Figure 5: Goals of care by dementia stage (modified from [69]).
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Page 8 of 12
hydration and antibiotic pneumonia treatment in advanced
dementia is very limited, so decisions are mostly based on
the individual circumstances. However, the potential bene-
fits of these interventions on patients’ survival and symp-
tom burden may be only transient [77].
In the terminal phase of dementia, continuous deep seda-
tion (CDS) may be discussed as a palliative care option. In
a recent Swiss study, about half of the decision-makers in-
cluded were open to CDS [78]. However, international da-
ta indicate that CDS in advanced dementia does not guar-
antee a dying process free from struggle or agony [79].
In Switzerland, assisted suicide is incompatible with ad-
vanced dementia due to the associated loss of decision-
making capacity [80].
Decisions in advanced dementia – including those for
health care – are usually not made by the patients them-
selves, but by their healthcare proxies, unless an advance
directive has been established. Clarifying the goals of any
care with the decision-makers, i.e., whether prolongation
of life span, maintaining or regaining functional abilities,
or comfort and well-being are the leading objectives, helps
to limit burdensome medical interventions in advanced de-
mentia [81]. In recent years, decision aids (e.g., evidence-
based brochures or videos) that support the shared deci-
sion-making process have become available [77,82]. In
order to provide optimal end-of-life care for persons with
advanced dementia, close cooperation between all the par-
ties involved is required. Future research and increasing
clinical experience will guide this process.
National Dementia Strategy Switzerland:
lessons learnt? (Stefanie Becker)
In order to respond to the growing challenges of dementia
disorders, the federal government and the cantons adopted
the “National Dementia Strategy 2014–2017” at the end
of November 2013 [83]. The preparatory work was initiat-
ed by a manifesto that the patient and family organisation
Alzheimer Switzerland had published back in 2008. In No-
vember 2016, the strategy was extended to 2019 because
the original time period was not – despite the great com-
mitment of the actors involved – sufficient to fully achieve
the project’s goals (fig. 6).
The superordinate goals were a better understanding of de-
mentia, its destigmatisation and the acceptance of those af-
fected by society. The strategy aimed to optimise the in-
teraction with, quality of treatment of and care for people
with dementia and to improve the quality of life of those
affected by dementia. This also includes providing demen-
tia-appropriate, integrated care throughout the course of
the disease, from early diagnosis to palliative care.
To achieve these goals, four fields of action and nine goals
were defined. The implementation was carried out using
a so-called multiplier approach, which was based on the
involvement of both national umbrella organisations and
specialist organisations (as multipliers of the results ob-
tained). However, public funds were not available for the
implementation of the strategy, and research into under-
standing the disease mechanistically was not part of the
National Dementia Strategy.
The evaluation showed that even though the strategy’s
medical and political importance was generally highly val-
ued, its goals could not be achieved as desired [84]. For
many of the organisations involved, the strategy provided
an important legitimisation for the investment of resources
in the subject area. However, the chosen implementation
concept and the lack of funding have both slowed the im-
plementation and led to the a-symmetrical participation of
mainly larger organisations. So far, those affected have
Figure 6: Action areas and goals of the National Dementia Strategy 2014–2019.
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Page 9 of 12
hardly benefited from the results. Undesired effects such
as the confusing proliferation of offers must now be coun-
tered with control and coordination to meet individual
needs.
In order to counter this criticism and to ensure that the re-
sources previously used have a lasting impact, a national
platform was launched after the strategy was completed. It
is intended to coordinate on-going and new activities under
one national umbrella, and thus contribute to the sustain-
able impact of the resources previously used. In addition to
the previous stakeholders, cantons, cities and municipali-
ties are now more involved. It remains to be seen whether
this structure will achieve noticeable results for people
with dementia and their relatives, even if there is still no
funding available.
Conclusions
While great progress has been made in basic and trans-
lational research into dementia diseases in recent years,
drug studies have so far failed. Now, after reanalysing two
phase III study results, a request for the approval of ad-
ucanumab, a mAb against Aβ, is in the process of being
submitted to the FDA. In China, sodium oligomannate has
been approved to treat AD. The substance therapeutical-
ly remodels gut microbiota and suppresses gut bacterial
amino acids-shaped neuroinflammation to inhibit AD pro-
gression. It remains unclear whether these new and poten-
tial future treatment options can significantly impact the
increasing number of people with dementia in Switzerland.
Such uncertainties call for substantial funding of basic and
clinical dementia research, as well as research translation.
Prevention remains an essential prerequisite to reducing
the incidence of dementia, as one third of dementia’s risk
factors can be modified. Preventing and treating sleep dis-
turbances may help to protect against dementia.
The development of clinical tests to assess social cognitive
dysfunction reliably, in an ecologically valid manner and
within a reasonable timeframe in order to improve the ear-
ly diagnosis and monitoring of the different dementia dis-
orders is very important.
A great challenge, both worldwide and in Switzerland, is
the improvement of care for people with dementia. Suc-
cessful assertive community treatment for the elderly has
been developed, and assistive technologies can help to
maintain home-dwelling. Awareness for delirium has im-
proved, but it remains under-recognised and undertreated.
Dementia is life-limiting and needs unique palliative care.
In order to provide optimal end-of-life care for persons
with advanced dementia, close cooperation between all the
parties involved is required.
In order to respond to the growing challenges of dementia
disorders, the National Dementia Strategy is an important,
but not a sufficient, instrument of health politics. National
funding and the inclusion of multiple stakeholders as well
as people with dementia add essential value to the devel-
opmental process and to the expected outcomes. Questions
of how, who and where to implement the results must be a
central part of a national strategy in order to achieve a sus-
tainable impact for those living with the condition.
It can be concluded that we will only be able to meet the
complex challenge of dementia through the interaction of
consultants, carers, researchers, politicians, and patient and
family associations, as well as business experts, patrons
and artists.
Potential competing interests
The panel of experts was sponsored by Merz and Vifor Pharma and all
authors received an honorarium from the two enterprises.
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