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Delirium, Dementia and "... I knew there was but One Way" Delirium Superimposed on Dementia: a Conceptual Approach

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Delirium as a severe, acute neuropsychiatric syndrome is common in older persons. The high prevalence of Delirium Superimposed on Dementia (DSD) can be explained by the fact that increasing age, cognitive impairment and dementia are all important risk factors for delirium. Failure of existing tools and current diagnostic criteria to reliably detect DSD emphasize the need for specific diagnostic criteria that account for pre-existing changes in cognition and behaviour as well as for the heterogeneity of delirium in brain diseases underlying dementia. Based on a review of time-honored clinical observations on delirium and current clinical observations on symptoms and course of DSD, diagnostic criteria are proposed to specifically detect DSD. Meticulous documentation of changes in pre-existing cognitive impairments, changes in levels of arousal and motor behaviour (wandering, pacing, carphology, floccillation) and the need for tailor made laboratory tests are emphasized in diagnosing DSD. Better recognition of DSD may lead to appropriate counseling and treatment that will facilitate alleviation of immediate suffering and possibly to prevention of accelerated functional decline as a consequence of DSD.
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Gerontology and Geriatric Research Open Access
Review Article
Delirium, Dementia and "... I knew there was but One Way"
Delirium Superimposed on Dementia: a Conceptual Approach
Van Gool WA1,2*, Oudewortel L2, and Hertogh CPM3
1Psychogeriatric Observation Unit, Institution for Mental Health Care, 'Dijk en Duin', Parnassiagroep, The Netherlands
2Department of Neurology, University of Amsterdam, The Netherlands
3Department of General Practice & Elderly Care Medicine, VU University Medical Center, The Netherlands
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Delirium, Dementia and "... I knew there was but One Way" Delirium Superimposed on Dementia: a Conceptual Approach. Gerontol
Geriatr Res. 2017; 1(1):112.
A R T I C L E I N F O
Article history:
Received: 01 August 2017
Accepted: 09 October 2017
Published: 01 November 2017
Keywords:
Delirium;
Dementia;
Delirium superimposed on dementia;
Neurodegenerative disease
Copyright: © 2017 Van Gool WA et al.,
Gerontol Geriatr Res
This is an open access article distributed
under the Creative Commons Attribution
License, which permits unrestricted use,
distribution, and reproduction in any
medium, provided the original work is
properly cited.
Citation this article: Van Gool WA,
Oudewortel L, Hertogh CPM. Delirium,
Dementia and "... I knew there was but One
Way" Delirium Superimposed on Dementia:
a Conceptual Approach. Gerontol Geriatr
Res. 2017; 1(1):112.
Correspondence:
Van Gool WA,
Department of Neurology,
Academic Medical Center,
University of Amsterdam, the
Netherlands,
Tel: +31-20-5664044;
Email: w.a.vangool@amc.uva.nl
A B S T R A C T
Delirium as a severe, acute neuropsychiatric syndrome is common in older
persons. The high prevalence of Delirium Superimposed on Dementia (DSD)
can be explained by the fact that increasing age, cognitive impairment and
dementia are all important risk factors for delirium. Failure of existing tools
and current diagnostic criteria to reliably detect DSD emphasize the need for
specific diagnostic criteria that account for pre-existing changes in cognition
and behaviour as well as for the heterogeneity of delirium in brain diseases
underlying dementia. Based on a review of time-honored clinical observations
on delirium and current clinical observations on symptoms and course of DSD,
diagnostic criteria are proposed to specifically detect DSD. Meticulous
documentation of changes in pre-existing cognitive impairments, changes in
levels of arousal and motor behaviour (wandering, pacing, carphology,
floccillation) and the need for tailor made laboratory tests are emphasized in
diagnosing DSD. Better recognition of DSD may lead to appropriate
counseling and treatment that will facilitate alleviation of immediate suffering
and possibly to prevention of accelerated functional decline as a consequence
of DSD.
Introduction
Most contemporary clinicians experience much more uncertainty in diagnosing
delirium or predicting its course, than Nell Quickly did in the case of Sir John
Falstaff in Shakespeare’s Henry V: “… for after I saw him fumble with the
sheets, and play with flowers, and smile upon his finger ends, I knew there was
but one way…” [1]. Especially in patients suffering from incipient cognitive
impairments or from clinically manifest dementia, clinicians have to answer
difficult questions on how exactly to disentangle the routes taken by dementia
and delirium. Can these pathways really be separated clearly, are they
intertwined, do they crisscross, where do they lead ultimately?
Delirium is a severe, acute neuropsychiatric syndrome that is common in older
persons. About 50% of older patients admitted to a hospital will develop
delirium and the prevalence in patients with pre-existing dementia is even up
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Delirium, Dementia and "... I knew there was but One Way" Delirium Superimposed on Dementia: a Conceptual Approach. Gerontol Geriatr Res. 2017;
1(1):112.
to 70%-90% depending on the severity of dementia
and the diagnostic methods used [2]. The high
prevalence of Delirium Superimposed on Dementia
(DSD) can be explained by the fact that increasing age,
cognitive impairment and dementia are all strong risk
factors for delirium [3]. DSD is associated with poor
outcomes, such as accelerated cognitive and functional
decline, and increased mortality [4,5]. Behavioural
disturbances in DSD are common and associated with
immediate, intense suffering in patients and with distress
in families and professional caregivers [6]. Due to
overlapping symptoms of delirium and dementia, DSD
remains unrecognized in up to 80% of cases in long term
care settings [7].
While the diagnosis of delirium can sometimes be
difficult in previously healthy older persons, detection of
delirium superimposed on pre-existing cognitive
impairment is extremely challenging from a clinical point
of view [6,7]. In these patients it is difficult to accurately
characterize newly occurring changes in attention, with a
fluctuating course, as the most prominent features of
delirium. Moreover, distinguishing increased impairments
of orientation, memory, thinking and behaviour as
symptoms of delirium from pre-existing cognitive
impairments is extremely difficult. Existing tools to detect
delirium may not be appropriate to detect delirium in
patients with pre-existing dementia [6]. Accurately
detecting DSD poses special and difficult diagnostic
challenges [8]. Classical diagnostic schemes like the
Diagnostic and Statistical Manual of Mental Disorders in
its most recent versions (DSM IV and V), preclude a
diagnosis of dementia in the face of delirium [9,10]. In
the opposite way, delirium should not be diagnosed
when symptoms can be “better accounted for by a pre-
existing, established, or evolving dementia” [11].
Moreover, in the DSM delirium is described as “a
reversible disorder due to medical conditions, substance
intoxication or withdrawal, or exposure to a toxin”.
However, in patients with dementia, episodes with
symptoms of delirium tend to last longer or they can
even be persistent, even if co-morbid medical conditions
are treated well [12,13].
Co-morbid delirium in older persons with either mild,
moderate or severe cognitive impairment requires
tailored counseling schemes and a balanced approach
to identify triggers and causes that can be treated as
the basis for personalized therapeutic interventions.
However, various authors have concluded that research
on DSD is hampered by the use of numerous different
screening tools, inconsistent criteria for its diagnosis,
reflecting the poorly conceptualized boundaries
between coexisting delirium and dementia [6,14]. The
field is caught in what has been characterized as a
“nosological swamp” [15]. Therefore, as a necessary
first step to advance the field, there is an urgent need
for a coherent diagnostic approach towards DSD. Based
on the medical literature on evolving concepts of
delirium and on recent differential diagnostic schemes
with strengths and weaknesses in identifying DSD, the
aim of this narrative review is to draft the outline of a
set of specific features for DSD. Combining insights from
ancient times with current knowledge may foster a new
portrayal of DSD that can facilitate its accurate and
reliable clinical recognition.
Historical Perspective
Although several earlier authors in antiquity, including
Hippocrates, had recognized the condition as well, Aulus
Cornelius Celsus was the first to use the term delirium in
medical writing in the 1st century AD [16,17]. Right from
these early days onwards, the use of a great variety of
terms for the very same or similar condition, may have
obfuscated a clear clinical view. In 500 BC, Hippocrates
referred to ‘phrenitis’ for delirium and in doing so he
described the all too familiar clinical sign of grasping at
imaginary objects: “As to the motions of the arms, I
observe the following facts. In acute fevers, pneumonia,
phrenitis and headache, if they move before the face,
hunt in the empty air, pluck nap from the bedclothes,
pick up bits, and snatch chaff from the walls all these
signs are bad, in fact deadly.-“ in this text fragment he
uses the ancient Greek "καρφολογία" (karphologia)
indicating literally "to behave as though one were
collecting straw" (Figure 1).
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While most authors recognized the temporary character
of behavioural problems of acute onset, sleep
disturbance and cognitive impairments associated with
fever, Celsus is the first to have noted that delirium may
not be reversible in all cases. He described some
patients continued to be insane after disappearance of
the cause of delirium, most notably using the word
‘dementia’ here: ”… insanity is really there when a
continuous dementia begins, when the patient, although
up till then in his sanity in his senses, yet entertains
certain vain imaginings; the insanity becomes established
when the mind becomes at the mercy of such imaginings”
[18]. In analogy to Hippocrates, Celsus also highlighted
abnormal hand movements in patients suffering from
delirium: “…picks with his hands at the flock or pulls at
the fringes of the bedclothes, or claws at anything small
projecting from the adjacent wall”, referring to the Latin
“floccus” for a piece of wool or straw [19].
Classical authors acknowledged that the restlessness,
insomnia and hallucinations of phrenitis could alternate
with episodes of inertia, quietness and sleepiness
(“lethargus”), both thought to be signs of brain disease.
During the medieval period and in later centuries,
writings continued on clinically similar episodes of
psychosis with cognitive function disturbances and motor
changes, using a variety of names like acute madness,
acute brain syndrome, exogenic mania, or intoxication
psychosis [17]. At the end of the 19th century the French
school of psychiatry initiated consolidation of these
previously differently named conditions into one name
“confusion mentale primitive”. The condition was
described as an acute brain disorder developing as a
result of organic disease, manifesting itself with
disturbance of cognitive functions with delusions,
hallucinations, psychomotor agitation or agitation as well
as inertia [20]. In 1817, Georg F.C. Greiner in his
discussion of delirium alluded to “…fogging of the light
of reason, and darkening of the objects of the
consciousness”. This early 19th century description was
reason for Adamis et al. to credit Greiner for
introducing the concept of the clouding of consciousness
as an imperative, defining feature of delirium [16]
(Figure 2).
The association of delirium with physical disease,
especially infections causing fever, was well recognized
throughout the medical history. With his early 20th
century descriptions of specific psychiatric syndromes,
including delirium, as ‘psychic reaction types’ to
exogenous factors, Bonhoeffer has been most influential
in shaping modern concepts of on the pathophysiology
of delirium [17]. Pivotal to Bonhoeffer’s view was the
observation that “The diversity of the underlying medical
conditions stands facing a great sameness of mental
conditions”. This led him to conclude that typical clinical
syndromes, such as delirium, are relatively independent
of specific causes. He postulated an ‘autotoxic agent’,
indicating that this could very well be ‘internal
disturbances, maybe those of the cerebral metabolism
[21]. This is an interpretation that may have special
merit in disentangling causal factors that contribute to
the symptoms of delirium in patients who also suffer
neurodegenerative disease with cognitive impairments.
However, before considering the etiology of DSD, its
accurate and reliable diagnosis should be considered.
1. The diagnosis of delirium in dementia
Figure 1: Hippocrates Prognostic iii-vi, IV. “As to the motions of the
arms, I observe the following facts. In acute fevers, pneumonia,
phrenitis and headache, if they move before the face, hunt in the
empty air, pluck nap from the bedclothes, pick up bits, and snatch
chaff from the walls all these signs are bad, in fact deadly”.
Figure 2: Title page (left panel) of ‘Der Traum und das
fieberhafteIrreseyn’ (1817) and an original text fragment (right
panel), highlighting: “Benebelung des Lichtes der Vernunft, und
Verdunkelung der Objectefür das Bewusstseyn”, which can be
translated as “fogging of the light of reason, and darkening of the
objects of the consciousness dominates”.
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1.1. Attention
Consistent with the historical descriptions cited above,
the current medical literature identifies different
important symptom clusters in delirium. Both, the
Diagnostic and Statistical Manual of Mental disorders-5
and the International Classification of Disease-10
identify disturbances of ‘attention’ and ‘awareness’ as
fundamental in delirium (Table 1) [10,22]. DSM-5
specifies the cardinal criterion for delirium as a
disturbance in attention as “reduced ability to direct,
focus, sustain, and shift attention” and awareness
(“reduced orientation to the environment”), while the ICD
using almost the same terminology, highlights the
“clouding of consciousness, i.e. reduced clarity of
awareness of the environment”, a phrasing strongly
reminding of Greiner’s “fogging of the light of reason”,
almost two hundred years earlier. Recently, the boards
of the European Delirium Association and the American
Delirium Association formulated a shared opinion on the
nature of the relation between attention and arousal, the
former relating to the content and the latter to the level
of consciousness. Both are hierarchically related as
completely normal levels of arousal do not preclude
profound inattention, whereas impaired arousal always
entails attentional deficits. DSM-5 stipulates in criterion
D that severely reduced levels of arousal such as coma
preclude a diagnosis of delirium, while the combined
delirium associations rightly emphasize that patients who
are not comatose but have a reduced level of
consciousness (‘drowsy’, ‘lethargic’, ‘obtunded’,
‘stuporous’ or ‘agitated’) precluding a reliable interview
or cognitive testing, are best characterized as severely
inattentive, and, as a consequence, classified as
suffering from delirium [23].
DSM nor ICD provide clinicians with any guidance on
how to reliably test at the bedside for impairments of
attention as core feature in their definition of delirium.
Several bedside assessment methods such as serial
sevens, digit span, or days of the week and months of
the year backwards, are used to probe attentional
integrity in subjects with (pre-existing) normal cognition.
If a patient with cognitive impairments of any degree of
severity fails one of these standard tests the question
arises however, if this failure indicates an impairment of
attention or can be readily explained by difficulties to
understand, memorize or execute the task.
Neurodegenerative or cerebrovascular disease causing
aphasia, agnosia, apraxia, executive or memory
impairments, may all affect the performance on
standard bedside tests of attention. Obviously, this
effect depends on the specific clinical characteristics of
the dementia syndrome and its global severity.
Predominant problems with comprehension of language
may affect test performance relatively early, while in
severe dementia, irrespective of the specific cognitive
impairments, hardly any patient may be capable to
complete the tests indicated above. In the light of the
clinical diagnosis of delirium, this may lead to the
spurious conclusion that there is a specific problem with
attention, fostering a false positive diagnosis of co-
morbid delirium in these patients. In a comprehensive
review of objective assessment methods of attention,
Tieges et al. conclude that based on group averages
delirium patients can be differentiated from dementia
patients using cancellation tasks, spatial span tests and
computerized tests of attention [24]. Results of individual
studies however suggest considerable overlap of test
scores, despite these group differences and, indeed, a
recent, comprehensive study of different tests of
attention shows rates of positive test results for
inattention of 40 to 50% in patients with dementia who
were in fact free of symptoms of delirium [25].
Observational scales may have the advantage of not
requiring an active role of the patient with dementia
who is assessed for the presence of delirium.
Impairments of comprehension or deficiencies in verbal
output or executive functions do not directly affect the
outcome of observations of behavioural patterns.
Interestingly, Tieges et al. report that observable
abnormal levels of arousal are a strong indicator of
delirium in acute hip fracture patients. Scales such as the
Observational Scale of Level of Arousal (OSLA) require
only a brief interaction with the patient, without the need
for any verbal response [26]. Total scores on this scale
are based on grading of four characteristics during
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about 60 seconds: the degree of stimulation required for
eye opening, time with appropriate eye contact, posture
on request to sit upright, frequency and characteristics of
spontaneous movements. The brevity and simplicity of
this scale make that repeated administration to detect
fluctuations of arousal will not put a heavy burden on
patients or physicians.
1.2. Cognition
In patients with intact cognition before the onset of
delirium, examination of orientation, memory, language,
visuospatial ability and executive functions, is
cornerstone in the diagnosis of delirium. Criterion B in
both the DSM-5 as the ICD-10 criteria (Table 1) reflects
this notion. In the DSM the relevance of the cognitive
state before the onset of delirium in evaluation of
observed impairments is acknowledged (“Should not be
better accounted for by a pre existing neurocognitive
disorder”). If this is interpreted narrowly as a
requirement not to consider any pre_existing cognitive
impairment as a sign of delirium, it would exclude the
diagnosis of delirium in the presence of any degree pre-
existing cognitive deficit. A more lenient interpretation
introduces the difficulty that the observed cognitive
impairment should be weighed against the cognitive
profile and severity of pre-existing impairments due to
e.g. pre-existing Alzheimer’s disease. In clinical practice,
the level of detail required for such a delicate
deliberation on the part of the examining clinician, will
be rarely available. Are the directly observable
cognitive impairments sufficiently explained by pre-
existing dementia or have they become excessive, so
that they may indicate co-existing delirium of recent
onset? A proper answer based on a bedside
examination can only be provided if the examining
Table 1: DSM-5 and ICD-10 diagnostic criteria for delirium in context of Delirium Superimposed on Dementia (DSD).
A. Disturbance in level of awareness and reduced ability to direct, focus, sustain,
and shift attention
Difficult to ascertain. Better to restrict to grading of level of
arousal?
B. Change in cognition (deficits in orientation, executive ability, language,
visuoperception, learning, and memory):
- Cannot be assessed in face of severely reduced level of awareness
- Should not be better accounted for by a pre_existing neurocognitive disorder
Interpretation of observed cognitive impairments should be
balanced with pre-existing deficits
C. There is evidence from the history, examination, or lab that the disturbance is
caused as a consequences of a general medical condition
Extensive investigations often fail to identify a general
medical condition that can explain delirium onset
D. The disturbance develops over a short period of time (usually hours to a few
days) and tends to fluctuate in severity during the course of a day.
Not essentially different in DSD from delirium without
dementia
E. Supportive features commonly present in delirium but not key diagnostic
features: sleep/wake cycle disturbance, psychomotor disturbance, perceptual
disturbances (e.g., hallucinations, illusions), emotional disturbances, delusions,
labile affect, dysarthria.
Features may occur in context of dementia without delirium.
Therefore, they lack diagnostic specificity in DSD
International Classification of Disease-10 Comment in relation to DSD
A. Clouding of consciousness, i.e. reduced clarity of awareness of the
environment, with reduced ability to
focus, sustain, or shift attention.
Difficult to ascertain. Better to restrict to grading of level of
arousal?
B. Disturbance of cognition, manifest by both:
(1) impairment of immediate recall and recent memory, with relatively intact
remote memory;
(2) disorientation in time, place or person.
Interpretation of observed cognitive impairments should be
balanced with pre-existing deficits
C. At least one of the following psychomotor disturbances:
(1) rapid, unpredictable shifts from hypo-activity to hyper-activity;
(2) increased reaction time;
(3) increased or decreased flow of speech;
(4) enhanced startle reaction.
Features may occur in context of dementia without delirium.
Therefore, they lack diagnostic specificity in DSD
D. Disturbance of sleep or the sleep-wake cycle, manifest by at least one of the
following:
(1) insomnia, which in severe cases may involve total sleep loss, with or without
daytime
drowsiness, or reversal of the sleep-wake cycle;
(2) nocturnal worsening of symptoms;
(3) disturbing dreams and nightmares which may continue as hallucinations or
illusions after awakening.
Features may occur in context of dementia without delirium.
Therefore, they lack diagnostic specificity in DSD
E. Rapid onset and fluctuations of the symptoms over the course of the day.
Not essentially different in DSD from delirium without
dementia
F. Objective evidence from history, physical and neurological examination or
laboratory tests of an underlying or systemic disease (other than psychoactive
substance-related) that can be presumed to be responsible for the clinical
manifestations in A-D.
Extensive investigations often fail to identify a general
medical condition that can explain delirium onset. In those
instances a neurodegenerative condition itself remains the sole
potential causal factor
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physician has a detailed and thorough knowledge of
both the nature and level of pre-existing impairments of
a given patient. This will not be the case in most of the
emergency room presentations or on first time
consultations on wards of general hospitals or even in
long-term care facilities. Even if a physician has
examined a patient some time before, a certain interval
between examinations may already preclude a proper
answer to the question indicated above. Information
obtained from families or informal or professional
caregivers may be helpful to a certain degree, but as a
rule this will not suffice to foster diagnostic certainty
concerning subtle changes in cognitive functioning.
Application of existing screening tools for delirium, all
tested and validated in patients free from pre-existing
cognitive impairments, can be expected to yield many
false positives in patients with pre-existing cognitive
impairments or clinically manifest dementia, especially in
advanced stages. Unconditional, straightforward
interpretation of this criterion (“B” in both classification
schemes) and its translation in operational clinical terms
is next to impossible in the diagnosis of DSD. This
suggests that the role of cognitive examination for
detection of DSD is fundamentally different than it is in
diagnosing delirium in populations free from cognitive
impairment.
1.3. The causal role of general medical conditions
Criterion C in DSM-5 and F in ICD-10 (Table 1) specify
that there is evidence from the history, examination, or
laboratory investigations that a general medical
condition underlies the delirium. According to the ICD-10
F criterion also a cerebral disease can be identified as a
sufficient cause of the delirium, whereas criterion C of
the DSM-5 suggests that failure to identify such a
general condition can be interpreted as an argument
against the diagnosis of delirium. Indeed, older people
with cognitive impairment or clinically manifest dementia
may become delirious through virtually any pre-existing
or newly occurring medical illness [5]. Premorbid chronic
diseases often influence the pre-test probabilities for
different causes or precipitating factors for delirium.
History of diabetes, for instance, may fuel suspicion of
hypo- or hyperglycemia. Also the medications used for
chronic diseases influence pre-test probabilities of
incident delirium. Therefore, the diagnostic approach
should vary according to the individual profile of clinical
symptoms. It is impossible to indicate every laboratory
test relevant in the search for causal factors of delirium.
Most common medical conditions and diseases are also
the most common causes for delirium. Laboratory
investigations should be designed to target the most
common conditions, such as infections, vascular diseases,
metabolic disturbance, and adverse medications [5].
Individual symptom profiles of patients with delirium
provide important clues to the possible causes of the
syndrome. Fever, for instance, raises high suspicion for
infection, and dyspnoea for cardio-pulmonary disease
[5].
Interpretation of diagnostic testing in older populations
with co-morbidities, is difficult. While in the general
population, specific medical conditions may play an
important role in delirium etiology, these may be less
robust in older populations. Urine culture, for example, is
definitely one of the most important laboratory tests for
delirium in general practice, but diagnostic
interpretation of a positive urine sample in case of
asymptomatic bacteriuria requires marked experience,
especially in Long Term Care Facilities (LTCF) settings.
Compared to relatively younger patients in general
hospitals, multiple predisposing and precipitating factors
may be more prevalent in older patients with DSD in
LTCF. Identification of a single, subtle, potentially
contributing factor to a florid delirium should not
withhold a vigorous search for further and more
important causes for delirium in individual cases.
However, in patients suffering from neurodegenerative
disease, it is quite common that extensive investigations
fail to convincingly identify any causal general medical
condition as a (potential) cause for delirium. In the ICD-
10 the potential causal role of brain disease itself is
acknowledged. In patients suffering from
neurodegenerative disease, underlying cognitive
impairments or dementia, other cerebral co-morbidity
like a strategic cerebral infarction or encephalitis may,
in theory, cause signs and symptoms of delirium.
However, it is much more likely that the very same
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neurodegenerative condition that caused the global,
cognitive deterioration also plays an important causal or
precipitating role in the symptoms of delirium. In e.g.
Alzheimer’s disease, Parkinson’s disease and
Huntington’s disease alike, the cholinergic system is
susceptible to neurodegeneration and cholinergic
deficiency is strongly associated with symptoms of
delirium, possibly operating as an example of
Bonhoeffer’s theoretical ‘internal disturbance’ in the
brain. So rather than questioning, as suggested by the C
criterion of DSM-5, which general medical condition may
have caused the delirium in a patient with dementia due
to a neurodegenerative disease, physicians may hold
the neurodegenerative disease itself responsible for the
clinical symptoms of delirium, in the sense of the criterion
F of the ICD-10. A practical consequence of this view is
that examinations aimed at the identification of medical
conditions potentially operative in DSD should be
tailored made based on individual characteristics of the
patient under investigation. Moreover, failure to identify
such a causative or precipitating factor should not be
interpreted as an argument against the diagnosis of
DSD.
1.4. Onset and course of symptoms
DSD seems not essentially different from delirium
occurring in patients with intact cognition with respect to
the onset and its fluctuating course. In all patients
delirium is characterized by its development over a short
period of time and its tendency to fluctuate in severity
during the course of a day (Table 1). DSD, however,
tends to take a more protracted course with increasing
severity of dementia. Symptoms seem to be more
resistant to symptomatic treatment and a in a
considerable number of patients DSD turns out to be
chronic without any signs of recovery. In a specific
subgroup of patients refractory symptoms of DSD seem
to be associated with impeding death [13].
1.5. Features supporting a diagnosis of delirium
Often neurodegenerative or cerebrovascular disease
causing dementia also gives rise to behavioural and
psychological symptoms that are associated with
delirium in other populations (Table 1). Estimates of the
frequency of symptoms such as irritability, agitation,
aggression, or psychosis outside the context of co-
morbid delirium vary widely in neurodegenerative
disease with study designs, clinical settings and spectrum
of patients studied with respect to diagnoses and
severity of dementia. Population-based studies generate
estimates for prevalence of delusions of 18%–25%,
hallucinations in 10%15% and agitation or aggression
in 9%30% of older persons with dementia [27-30]. In
clinical or institutionalized populations point estimates for
prevalence tend to be even higher, ranging for patients
with Alzheimer’s disease from, to 36% for delusions, and
41% for psychosis [27, 31]. Proper interpretation of
these clinical features as supporting a diagnosis of
delirium that are specified in both DSM-5 and ICD-10,
therefore, is difficult in subjects with neurodegenerative
or cerebrovascular vascular disease causing dementia.
Sleep/wake and psychomotor changes, emotional
disturbances, labile affect, increased reaction times and
startle reactions (Table 1) may all very well occur in the
context of dementia, without any (other) sign of delirium.
Therefore, clinical observation of these features lack
specificity for diagnosing DSD and if used without
restrictions they may foster many false positive DSD
diagnoses.
2. Delirium and dementia in context
Dementia and delirium may be difficult to disentangle
even if a reliable informant can provide the essential
information on previous levels of functioning, even if
results of careful observations from informal or
professional caregivers are available, and even after
performing a skillful bedside examination. One
important factor that contributes to this difficulty is the
fact that both dementia and delirium are consequences
of brain failure, similarly as a diagnosis of Wernicke
aphasia can be difficult in a manic patient or symptoms
of apathy in depression can be difficult to delineate
from lack of initiative in white matter disease. In a recent
commentary Suh and Gega refer to classical literature
characterizing delirium as acute brain failure, in contrast
to dementia being a consequence of chronic brain
failure [32]. In this view delirium in dementia relates to
pre-delirium cognitive impairments as acute
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1(1):112.
exacerbations in renal or pulmonary disease may be
superimposed on chronic renal failure or chronic
obstructive pulmonary disease. Analogous to those
interactions in different organ systems, also patients
suffering from dementia as a result of
neurodegenerative disease may be subject to sudden
deterioration, despite the common wisdom that the
underlying neurodegenerative disease tends to have a
gradual course. In all these chronic conditions with renal,
pulmonary or brain disease, acute exacerbations may
occur that all require timely interventions trying to
recover functions of the organ system involved in order
to first alleviate immediate distress associated with the
exacerbation and secondly to avoid further decline
(Figure 3).
A second factor that contributes to the diagnostic
difficulty is the fact that the very nature of co-morbid
delirium may be subject to change during the course of
neurodegenerative disease. In the absence of
neurodegenerative disease (Example 1, Figure 3), in
cognitively intact older persons, the threshold for
developing delirium symptoms is large. Only severe
disease such as e.g. sepsis may cause a prototypical
delirium as it is outlined in standard textbooks: a short
lasting period of confusion from which the patient fully
reverts to normal levels of cognitive functioning. If,
however, a subject develops mild cognitive impairments
due to early neurodegenerative disease the distance to
a hypothetical delirium-threshold may be decreased (cf.
Example 2, Figure 3). A simple infection that is otherwise
uncomplicated or discomfort caused by pain or
constipation for example may be sufficient already to
elicit an episode with delirium. In this context delirium
tends to be more severe and to last longer. After
appropriate treatment of the causal factors, symptoms
of delirium may wane, but as noted before this type of
delirium tends to contradict common clinical wisdom on
two accounts [13]. While delirium is generally
considered to be a transient state that responds well to
correction of precipitating factors and symptomatic
treatment, in these cases patients may never return
completely to their pre-existing level of functioning
anymore (Example 2, Figure 3). Secondly,
neurodegenerative diseases are commonly described as
gradually progressive from a clinical perspective, but in
this clinical situation severe delirium lasting longer than
average can be associated with an apparent sudden
clinical deterioration (grey arrow in Figure 3). At the
stage of severe dementia as a result of advanced
neurodegenerative disease, patients may fluctuate
around the delirium threshold, as illustrated by example
3 in figure 3. Compared to delirium patients without
pre-existing cognitive impairment, delirium in DSD has
more pronounced fluctuations and is more frequently
associated with increased response latency to verbal
stimuli, aggressive behaviour, anxiousness, agitation,
restlessness and hallucinations [33]. As indicated above,
often no other cause for delirium than advanced
neurodegenerative disease itself can be identified in
these cases. Advanced neurodegeneration, e.g. in the
cholinergic system, or increased neuroinflammatory tone,
or a combination thereof, can perhaps be viewed as
reflections of Bonhoeffer’s ‘internal disturbance’ as
discussed earlier. A delirium of this kind is likely to
worsen over time and any improvement is likely to be
slower and more fluctuating. Cole and McCusker
recently proposed that in some clinical situations,
delirium is characterized by a chronic fluctuating course,
periods of acute exacerbation and increasing symptom
frequency [34]. If these symptoms persist they become
associated with poor clinical outcomes and ultimately,
Figure 3: The thick blue line depicts the course of global cognitive
functioning, deteriorating over time as a result of
neurodegenerative disease. The ordinate represents levels of
global cognitive function and the shaded blue area degrees of
attentional deficits, where delirium symptoms increase
(downwards) according to intensity of the coloring. Superimposed
are three episodes of delirium taking a different course according
to the severity of neurodegeneration, which increases over time.
For further explanation see text.
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Delirium, Dementia and "... I knew there was but One Way" Delirium Superimposed on Dementia: a Conceptual Approach. Gerontol Geriatr Res. 2017;
1(1):112.
diagnostic differentiation between clinical signs of
delirium and advanced dementia may become next to
impossible, especially in a condition such as Lewy body
dementia or dementia in Parkinson’s disease,
characterized by clinical fluctuations, prominent
impairments of attention and frequent hallucinations
[35].
3. A proposal for specific diagnostic criteria for
delirium superimposed on dementia
The diagnosis of DSD requires specific diagnostic
criteria. Inspired by some of the historical descriptions
cited above and by current insights concerning symptom
clusters in delirium, we draft here an outline of a set of
features that may facilitate accurate and reliable
recognition of DSD (Table 2).
Any sudden deterioration in a patient with previously
diagnosed dementia or cognitive impairment should
raise the concern of DSD, requiring immediate and
specific diagnostic expertise. DSD cannot be diagnosed
without any evidence of pre-existing cognitive decline
from either the medical history, an informant interview,
or clinical observation preceding the current
deterioration (Criterion A, Table 2). The Informant
Questionnaire on Cognitive Decline in the Elderly
(IQCODE) is a reliable instrument to obtain the relevant
information in a structured way [36].
A survey of a large group of delirium experts showed
that most respondents identified impaired attention and
fluctuation in cognitive status as the most useful features
in diagnosing DSD [37], perhaps based on observations
indicating that DSD is associated with more severe
impairments of arousal and awareness [38]. Performing
standard bedside tests of attention require a certain
level of understanding and cooperation of the patient
under examination. Depending on the severity of
dementia such tests may elicit false positive test results
with respect to the detection of DSD (Oudewortel et al.
manuscript in preparation). Therefore, mere observation
of the level of arousal represents an attractive
alternative for obtaining information pertaining to the
proposed criterion B (Table 2) [26]. It requires only
minimal cooperation of subjects and level of arousal is
closely associated with attention deficits and occurrence
of delirium in older populations. Exploration is
warranted of the test characteristics for the detection of
delirium of observational scales like the OSLA in patients
with either dementia in isolation or DSD.
Criterion C (Table 2) detailing the course of symptoms is
similar to the generic definitions of delirium as specified
in the DSM and ICD. The fluctuations may be more
profound and the course more protracted in severe DSD.
As brain diseases that cause dementia may be
accompanied by a variety of behavioural, affective and
motor changes, not necessarily implying presence of
delirium, criterion D (Table 2) requires presence of at
least two of hallucinations, delusions, changes of affect,
or changed motor behaviour. Motor changes may
involve hypo- or bradykinesia or wandering and pacing.
Studies of symptom profiles of delirium in patients with
or without dementia indicate that psychomotor agitation
occurs more frequently in DSD [33, 39]. The classical
descriptions of aimless plucking at objects, either
imaginary or real, as in the classical descriptions of
Hippocrates and Celsus may have special significance
Table 2: Proposed diagnostic criteria for delirium superimposed on
dementia and guidance for their clinical application.
A. Pre-existing dementia or
cognitive impairment
Documented in medical history or
from informant interview eg
IQCODE
B. Disturbance of arousal or
attention; inability to direct,
focus, sustain or shift attention
Examination; months of the year
backwards, counting 20 to 1,
selective response on
presentation of stimuli, e.g. a
series of letters: CASABLANCA,
or observation of arousal,
depending on the severity of
dementia
C. Change of previous level of
functioning that:
1. Developed over a short
period of time (hours to a few
days), and
2. Represents a distinct
change from pre-existing levels
of impairment, and
3. Tends to fluctuate during
the course of a day
Based on available information
from medical history or informant
interview (criterion C1 and C2)
and clinical observation (criterion
C3)
D. Criterion A, B and C are
accompanied by at least two
of: hallucinations, delusions,
labile affect, or changed motor
behavior (deceased or
increased: wandering, pacing,
carphology, floccillation)
Clinical examination and
continued observation
E. Evidence from history,
physical and neurological
examination or laboratory tests
that it is unlikely that systemic
disease is responsible for the
clinical manifestations in A-D.
History physical, neurological
examination and tailored
laboratory tests
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Delirium, Dementia and "... I knew there was but One Way" Delirium Superimposed on Dementia: a Conceptual Approach. Gerontol Geriatr Res. 2017;
1(1):112.
here. Holt et al. describe that carphology (aimlessly
picking at bedclothes) and floccillation (plucking at the
air) may be relatively uncommon, but that their presence
is highly suggestive of delirium in older patients with a
specificity over 0.9 [40]. The final, exclusionary criterion
(E, Table 2) of the absence of evidence that systemic
disease is responsible for the clinical deterioration, but
that the cause of delirium should be localized in the
brain itself can be viewed as an echo of Bonhoeffer’s
reference to an autolytic agent. Decreased fractional
anisotropy in the presumably cholinergic projections
from the nucleus basalis that are associated with
delirium-like symptoms can perhaps serve as a more
contemporary example of this factor [41].
The proposed diagnostic criteria for SDS (Table 2) may
not be spectacularly different from the generic criteria
for delirium of the DSM or ICD. However, important
adaptations of these criteria concern the requirement of
pre-existing dementia or cognitive impairment, more
emphasis on the observation of the level of arousal
(rather than on bedside tests of attention) in suspected
DSD, less emphasis on bedside tests of cognition, a more
formal role of changed motor behaviour and a less
prominent role for evidence that DSD is caused as a
consequence of a general medical condition. The latter
consideration, however, does not absolve physicians
from the need of a thorough physical examination in
cases of suspected DSD, but it may invite some self-
restraint with respect to laboratory examinations or X-
rays.
Conclusion
Generic criteria for the clinical diagnosis of delirium
from either the DSM or ICD are insufficient for reliable
detection of DSD. Application of these criteria that
relate to cognitive impairments or specific behavioural
and psychological symptoms will lead to false positive
diagnoses of delirium in patients with dementia or even
in subjects with mild cognitive impairments. On the other
hand changes in cognition or behaviour may also be too
easily explained away with reference to progression of
pre-existing neurodegenerative or cerebrovascular
disease fostering false negative diagnoses of DSD.
Therefore, the concept of DSD requires specific
diagnostic criteria that account for pre-existing changes
in cognition and behaviour as well as for the changing
characteristics of delirium depending on the stage of
dementia. Time-honored clinical observations such as
those on floccillation, carphology and clouding of
consciousness according to Geiner, or Bonhoeffer's
concept of an autolytic agent in the brain, merit full
reconsideration with respect to the clinical and
nosological problems surrounding DSD. Ultimately, this
may help to better recognize DSD and to facilitate
early detection allowing for appropriate counseling and
treatment. This has the potential to alleviate immediate
suffering in DSD, to prevent accelerated decline and,
thus, to avoid the ominous “one way”, as professed by
Shakespeare’s Falstaff.
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... Blinded for the nurses' DIDAS score, a geriatric physician or senior geriatric nurse practitioner independently assessed presence and severity of any deliriumsymptom each day based on their own clinical observations, reports from colleagues, and other information from the electronic patient file. This clinical assessment was used to diagnose (or refute) DSD based on conceptcriteria for diagnosing a DSD as proposed by van Gool et al., [17,18]. ...
... The main limitation to this study may be that there is no golden standard for the diagnosis of DSD nor for measures of severity in this condition. Therefore, the reference standard for both in this study was based on the clinical assessments by independent observers, experienced geriatric physicians or a specialized senior nurse practitioner, applying concept criteria for DSD [18]. Because several items that are assessed in the DIDAS (fluctuations, attention and consciousness) are also key criteria of the reference standard for DSD diagnosis, they might therefore have inflated the sensitivity as well as the discriminative power of the DIDAS. ...
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Delirium and dementia are two of the most common causes of cognitive impairment in older populations, yet their interrelation remains poorly understood. Previous studies have shown that dementia is the leading risk factor for delirium and that delirium is an independent risk factor for subsequent development of dementia. However, a major area of controversy is whether delirium is simply a marker of vulnerability to dementia, whether the effect of delirium is solely related to its precipitating factors, or whether delirium itself can cause permanent neuronal damage and lead to dementia. Ultimately, all of these hypotheses are likely to be true. Emerging evidence from epidemiological, clinicopathological, neuroimaging, biomarker, and experimental studies lends support to a strong relation between delirium and dementia, and to both shared and distinct pathological mechanisms. New preventive and therapeutic approaches that target delirium might offer a sought-after opportunity for early intervention, preservation of cognitive reserve, and prevention of irreversible cognitive decline in ageing. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Delirium was one of the first mental disorders ever to be described, though it remains an elusive concept to this day. Historically, delirium has developed from the prototype of acute confusion with psychomotor agitation. It was thought to be caused by the withdrawal of substance dependence or severe somatic diseases accompanying by fever; however only in the 20th century, it was concluded that delirium and similar states manifest themselves as a consciousness disorder, and is not a specific state of somatic diseases. Four core features defines delirium at present: a disturbance of consciousness, a disturbance of cognition, limited course and external causation. However, these features do not include common manifestations of delirium in elderly patients with dementia; therefore the concept of delirium should be revised and corrected.
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