Maturitas Vascular cognitive impairment in dementia

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Maturitas Vascular cognitive impairment in dementia
Maturitas 79 (2014) 220–226
Contents lists available at ScienceDirect
Maturitas
journal homepage: www.elsevier.com/locate/maturitas
Review
Vascular cognitive impairment in dementia
Christopher D. Etherton-Beer a,b,∗
a
Western Australian Centre for Health & Ageing (M573), Centre for Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA
6009, Australia
b
Department of Geriatric Medicine, Royal Perth Hospital, 197 Wellington Street, Perth, WA 6000, Australia
a r t i c l e
i n f o
Keywords:
Dementia
Vascular
Cerebrovascular disorders
Cerebral infarction
Brain ischaemia
a b s t r a c t
Vascular risk factors and cerebrovascular disease are common causes of dementia. Shared risk factors
for vascular dementia and Alzheimer’s disease, as well as frequent coexistence of these pathologies in
cognitively impaired older people, suggests convergence of the aetiology, prevention and management
of the commonest dementias affecting older people. In light of this understanding, the cognitive impairment associated with cerebrovascular disease is an increasingly important and recognised area of the
medicine of older people. Although the incidence of cerebrovascular events is declining in many populations, the overall burden associated with brain vascular disease will continue to increase associated with
population ageing. A spectrum of cognitive disorders related to cerebrovascular disease is now recognised. Cerebrovascular disease in older people is associated with specific clinical and imaging findings.
Although prevention remains the cornerstone of management, the diagnosis of brain vascular disease
is important because of the potential to improve clinical outcomes through clear diagnosis, enhanced
control of risk factors, lifestyle interventions and secondary prevention. Specific pharmacological intervention may also be indicated for some patients with cognitive impairment and cerebrovascular disease.
However the evidence base to guide intervention remains relatively sparse.
© 2014 Elsevier Ireland Ltd. All rights reserved.
Contents
1.
2.
3.
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11.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Aetiology and convergence of risk factors for the major dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anatomic and functional correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical correlates and differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment of vascular cognitive impairment in dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
What is the current state of the art? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appendix A.
Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
∗ Correspondence to: Western Australian Centre for Health & Ageing (M573),
Centre for Medical Research, University of Western Australia, 35 Stirling Highway,
Crawley, WA 6009, Australia. Tel.: +61 8 9224 2750; fax: +61 8 9224 8009.
E-mail address: Christopher.etherton-beer@uwa.edu.au
http://dx.doi.org/10.1016/j.maturitas.2014.06.004
0378-5122/© 2014 Elsevier Ireland Ltd. All rights reserved.
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1. Introduction
Ageing populations face an increase in disease burden from
chronic neurodegenerative conditions. Dementia will be a major
contributor to this increased burden [1]. Cerebrovascular disease is
thought to be the second most common cause of dementia and a
spectrum of cognitive disorders related to cerebrovascular disease
is now recognised [2]. Accordingly, the cognitive impairment associated with brain vascular disease is an increasingly important and
recognised area of the medicine of older people. Despite the critical importance of dementia, there is still inconsistent definition of
the major sub-types. There is increasing recognition that many, if
not most, older people with dementia have mixed, or overlapping,
disease due to both vascular and Alzheimer’s type changes. However the concept of “mixed dementia” remains variably recognised
and operationalised. In this context, the nature, importance and
management of vascular cognitive impairment are reviewed.
2. Methods
This narrative review provides a brief overview of traditional
teaching, and more recent research findings, relevant to clinical
practitioners in the field ordered using a clinical approach. In addition, the “state of the art” was specifically considered in a search of
the Medline indexed English language human studies published in
the last 12 months (to April 2014) using the search terms “dementia” or “Alzheimer disease”, and “cerebrovascular disorders” or
“stroke” or “cerebral infarction” or “brain ischemia”. Studies not
specifically related to the relationship between cerebral vascular
disease and cognitive impairment/dementia were excluded, as well
as protocol papers and letters.
3. Clinical definitions
Traditional teaching described vascular (or “multi-infarct”)
dementia as the second leading type of dementia, usually with
relatively abrupt onset and stepwise decline, related to multiple
large volume or lacunar brain infarcts. Also included were people who may have had fewer strokes, but the strategic position
of the lesions(s) and temporal relationship to the onset of cognitive impairment suggested aetiological relevance. Increasingly
a broader spectrum of cognitive disorders associated with brain
cerebrovascular disease has been recognised. It is now accepted
that diffuse white matter disease (as distinct from circumscribed
infarction) is a common cause of vascular cognitive impairment
[3]. This spectrum includes people who may not be aware of ever
having had a “stroke” or brain vascular disease, but who nonetheless have sub-cortical (white matter) disease [4] sufficient to cause
clinically relevant cognitive and physical signs. Reflecting this progression in the understanding of brain vascular diseases, DSM now
refers to major and mild vascular neurocognitive disorder, and continues to provide specific criteria for an assumed vascular basis of
the cognitive impairment [5]. “Vascular cognitive impairment” is
the descriptor now in general use encompassing this spectrum of
vascular brain disorders [6].
In addition to the DSM criteria, several other clinical criteria
and scoring systems have been utilised. Early scoring systems [7]
distinguished presumed vascular ischaemic aetiology based on the
history of abrupt onset, stroke, or hypertension, the presence of
hypertension or focal neurological symptoms or signs, a stepwise
deterioration, somatic complaints and emotional lability. Subsequent criteria also included imaging evidence of cerebrovascular
disease and additional clinical features such as the early presence of a gait disturbance or falls, incontinence, pseudobulbar
palsy, and additional neuropsychiatric signs (personality change,
Fig. 1. Periventricular hypodensity, and atrophy, on CT.
abulia, depression, psycho-motor retardation and impaired executive function) [8,9].
4. Aetiology and convergence of risk factors for the major
dementias
Age and the major traditional vascular risk factors (hypertension, smoking, diabetes and hypercholesterolemia) account for the
majority of a person’s lifetime risk of cardiovascular events [10].
The presence of vascular risk factors such as hypertension and diabetes in midlife is negatively associated with subsequent cognitive
function in older age [11,12]. In addition to predicting atherosclerotic disease, these “vascular” risk factors also predict, and appear
to promote development of, Alzheimer’s disease [13,14]. Data
regarding the progression over time of established Alzheimer’s
dementia are not conclusive, but suggest association of vascular risk factors with progression of cognitive decline in some
groups of patients [15]. Other shared risk factors for both vascular
and Alzheimer’s disease include hyperhomocysteinaemia [16,17],
inflammation [14,18], and genetic variants [19]. Depression is a
possible further shared risk factor for both vascular and Alzheimer’s
dementia [20], although residual confounding (for example, by subcortical brain vascular disease) cannot be excluded.
Traditional teaching has emphasised the presumed atherosclerotic aetiology of white matter disease. However white matter
changes may relate both to arteriolar disease and venulopathy,
as well as other processes such as ependymal leakage, oedema
due to blood brain barrier disruption and endothelial activation
[35]. Venular disease may be particularly important in the typical
periventricular white matter changes seen around the anterior and
posterior horns (Fig. 1) [35].
5. Epidemiology
Given that dementia and vascular disease are strongly age
related, population ageing will be associated with absolute
increases in the overall burden of dementia and stroke. Stroke
and dementia frequently co-exist; around one in ten patients have
dementia prior to their first stroke, increasing to one in five within
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the first year after first stroke, and over one in three within the first
year after recurrent stroke [21]. Relatively, chronic neurodegenerative conditions (of which dementia is foremost) are anticipated to
be an increasingly important cause of death and disability [1]. Age
standardised death rates from Alzhemier’s dementia are increasing [22]. This increase in the relative importance of mortality from
dementia is in the context of substantial decreases in incidence of,
and mortality associated with, cardiovascular and cerebrovascular disease [23]. These improvements are thought to be related to
more effective control of traditional vascular risk factors, as well
as enhanced medical interventions and care (such as coronary care
units).
6. Anatomic and functional correlates
Traditional teaching emphasised the distinct pathological processes of vascular disease and neurodegeneration secondary to
Alzheimer’s pathology. These distinctions now appear to be less
relevant clinically, given that people surviving to old age frequently
have co-existent changes of both Alzheimer’s type pathology and
vascular disease [24]. Healthy adults have substantial cerebral
reserve and thus many older people have sub-clinical disease. For
example, it is not uncommon for an older person with no memory
complaints to have imaging evidence of vascular brain disease. The
commonest imaging findings, mild periventricular changes, may
have limited clinical impact on the patient’s cognitive function or
gait [25]. It may be intuitive to assume that large volume brain
changes are more likely to be associated with clinically obvious cognitive impairment. However, cognitive impairment appears to be
common after both lacunar (small volume) and non-lacunar stroke
[3], perhaps in part because of the common association of lacunes
with small vessel disease.
Brain changes of established ischaemic vascular disease appear
hypodense (dark) on CT, hypointense (dark) on T1 weighted MRI
and hyperintense (bright) on T2 weighted MRI sequences [26].
Whilst specific stroke lesions are usually circumscribed they are
heterogeneous, ranging from small, deep lacunar infarcts to large
volume hemispheric infarcts, and from single to multiple (Fig. 2)
synchronous acute lesions. Subcortical white matter (in distinction
from cortical “grey matter”) changes may be punctate, or when
advanced, more confluent. Periventricular changes are usually most
pronounced around the anterior and posterior horns of the lateral
ventricles. Deep white matter changes are sub-cortical changes that
are not immediately periventricular. Subcortical changes are commonly described as “small vessel disease” (in distinction to stroke
due to large artery embolism). Other historical terms (such as the
eponymous “Binswanger’s disease”) are descriptions of advanced
subcortical disease, and the associated clinical syndrome. These
terminologies can be used imprecisely, leading some authors to
propose new nomenclature [27].
In addition to ischaemia, white matter disease is associated
with micro-haemorrhage. Increasing use of (more sensitive) MRI
has revealed that micro-bleeds are more common than previously appreciated [28]. Like large volume bleeds, the distribution
of micro-bleeds is thought to vary according to aetiology, with
lobar micro-bleeds being suggestive of amyloid angiopathy and
involvement of deep structures such as the basal ganglia and thalamus more suggestive of a hypertensive aetiology [28]. Atrophy
is another common structural brain change identified on imaging.
Although it is usually assumed that substantial atrophy is clinically
relevant, maximal brain volume may confound observed associations between atrophy and cognitive deficit [29].
Semi-quantitative rating of brain images is both reliable and
valid [30]. Sulcal widening (SW) and ventricular enlargement
(VE) can be rated by comparison to a standard reference image
that shows moderate brain changes. Periventricular white matter
changes (PVWMC) and deep white matter changes (DWMC) can be
rated using the method originally described by Fazekas et al. [31]
(Fig. 3). For PVWMC, a rating of ‘0’ indicates no changes, ‘1’ indicates
‘caps’ or pencil-thin periventricular bands, ‘2’ indicates a smooth
‘halo’ and 3 indicates irregular periventricular changes extending
into deep white matter. For DWMC ‘0’ indicates no changes, ‘1’ indicates punctate foci, ‘2’ beginning confluence of foci and ‘3’ large
confluent areas.
Stroke is a risk factor for cognitive impairment and vice versa
[21], suggesting an interplay between the pathophysiologic processes underlying both clinical conditions. Specifically, there are
several potential mechanisms for interaction between brain vascular disease and Alzhemier’s disease, both at the biological and
clinical levels. At the biological level shared pathophysiology
(including increased oxidative stress, impaired vascular function
[32], and arterial stiffness [33]), and direct interactions between
the two pathological processes (such as ischaemia promoting
Alzheimer’s pathology, and vice versa) may be relevant [13]. At the
clinical level, vascular disease could contribute to, or unmask, cognitive impairment also contributed to by Alzheimer’s type changes,
and vice versa [14].
7. Clinical correlates and differential diagnosis
Fig. 2. Multiple acute infarcts (hyperintensity) demonstrated on diffusion weighted
MRI.
Structural vascular brain disease is thought to cause cognitive
impairment through strategic cortical infarcts, infarction of the
basal ganglia or thalamus, or disruption of white matter tracts
by lacunar infarcts or small vessel disease. Strategic infarcts will
cause a pattern of cognitive deficits according to the infarct location
[34]. Subcortical vascular cognitive impairment is characterised by
relative preservation of memory with impaired cognitive speed,
attention and executive function (including impaired initiation,
planning and sequencing). Important additional behavioural or
psychiatric features can include depression, apathy, and psychosis
[6,26]. Early findings (such as a modest degree of cognitive slowing)
are often compensated, and in the absence of functional impairment a high index of clinical suspicion is required. In addition,
executive dysfunction may not be detected by screening tools in
common use (such as the Mini Mental State Examination). Because
C.D. Etherton-Beer / Maturitas 79 (2014) 220–226
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Fig. 3. Fazekas scale grading of white matter hyperintensities
reproduced with permission, see acknowledgements.
of the cognitive slowing and psychomotor retardation that can be
associated with brain vascular disease, depression is an important
differential diagnosis.
Larger volume (anterior and posterior circulation) and lacunar
infarcts are associated with characteristic clinical syndromes [35].
In addition to the cognitive changes, it has long been appreciated
that substantial ischaemic brain disease is commonly associated
with clinical features including bilateral upper motor neurone signs
(such as brisk reflexes), gait disorder and urinary incontinence [36].
The characteristic parkinsonian gait disorder (“vascular parkinsonism”, “marche a petits pas”, “magnetic”, “apraxic–ataxic”) may be
associated with a history of unsteadiness and frequent, unprovoked
falls. Vascular disease is thought to cause at least 5% of cases of
parkinsonism in older people [37]. The physical signs are sometimes characterised as “lower half parkinsonism” because of the
parkinsonian gait disorder, but absence of prominent upper body
signs of idiopathic Parkinson’s disease, such as tremor. The signs are
also often bilateral, whereas idiopathic Parkinson’s disease tends to
cause prominent asymmetric signs such as tremor and rigidity.
Clinical findings are important to clarify the relevance of structural changes noted on brain imaging. For example, if a patient is
free from physical signs, modest white matter changes on imaging
may be of uncertain clinical significance. However, imaging findings of substantial vascular brain disease are likely to be clinically
relevant in a patient with upper motor neurone signs, gait disorder
and a pattern of subcortical cognitive impairment.
8. Prevention
Given the challenge of reversing established brain vascular
disease, prevention is a cornerstone of management. Lifestyle
interventions, including physical and cognitive activity are often
recommended to maintain wellbeing in middle and later life. There
is evidence that physical activity has beneficial effects on endothelial function [32] and may prevent cognitive impairment [38].
Improved control of vascular risk factors in mid-life is assumed to
be a key strategy to reduce the burden of vascular cognitive impairment in ageing populations. Controlled (but non-randomised) data
support the notion that an active prevention programme (targeting
treatment of vascular risk factors in middle aged people) can reduce
the need for long term care, by about 10% [39]. However, uncertainties persist regarding the benefits of specific pharmacotherapies
in prevention of cognitive impairment. Despite epidemiologic evidence suggesting that statins reduce the risk of Alzheimer’s disease,
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Table 1
State of the Art: brief summary.
Study
Participants
Main finding
Associations between serum cholesterol
levels and cerebral amyloidosis (Reed 2014
[49])
74 older people recruited from clinics or
the community, most with normal
cognition (n = 33) or mild cognitive
impairment (n = 38)
177 older adults free from stroke or
cognitive impairment
Higher low density lipoprotein cholesterol and lower high
density lipoprotein cholesterol levels, but not statin use, were
independently associated with a greater burden of cerebral
amyloid
Pulse pressure was independently associated with
cerebrospinal fluid biomarkers of Alzheimer’s disease
203 patients with amnestic mild cognitive
impairment
In people converting to AD (n = 74) WMHs were associated
with decreased frontal, but not temporoparietal, metabolism.
In contrast, low cerebrospinal fluid ␤-amyloid (a biomarker of
Alzheimer’s disease) was associated with temporoparietal, but
not frontal, hypometabolism
Cerebral atherosclerosis was positively associated with
vascular disease but not Alzheimer’s type disease pathology.
Cerebral amyloid angiopathy was inversely associated with
lacunar infarcts and positively associated with Alzheimer’s
type changes
Impaired executive function predicted stroke and Alzheimer’s
disease. Low total brain volume and white matter
hyperintensity volume were associated with stroke, but not
Alzheimer’s disease. In contrast, low hippocampal volume
predicted Alzheimer’s disease
Association of pulse pressure with
biomarkers of Alzheimer’s disease in
cognitively normal older adults (Nation
2013 [50])
Association of Alzheimer’s disease markers
and white matter hyperintensities (WMH)
with brain metabolism (Haight 2013 [51])
Association of cerebral atherosclerosis
with vascular, but not Alzheimer’s type,
pathologic changes (Zheng 2013 [52])
Autopsy sub-study (n = 163) of participants
from a longitudinal study of subcortical
ischaemic vascular disease, Alzheimer’s
disease, and normal ageing
Brain imaging and cognitive predictors of
stroke and Alzheimer’s disease in the
Framingham Heart Study (Weinstein 2013
[53])
1679 Framingham offspring (age >55
years; mean, 65.7 ± 7.0) free from
dementia and stroke
intervention trials to date have failed to demonstrate that statin
therapy can prevent the development of cognitive problems [40].
Similarly, despite the epidemiologic evidence identifying hypertension as a risk factor for cognitive impairment, the overall
randomised data do not conclusively demonstrate that antihypertensive therapy can prevent cognitive impairment [41].
9. Treatment of vascular cognitive impairment in dementia
Although traditional teaching was that nervous system lesions
were essentially irreversible, the potential for plasticity of the nervous system is increasingly recognised. Neuroplasticity persists in
ageing brains, and facilitates recovery from acute stroke lesions
[42]. The potential for plastic remodelling in the face of neurodegeneration or chronic small vessel disease is less well understood.
Systematic review of the randomised studies of cognitive rehabilitation or cognitive training in people with dementia suggests
limited efficacy, although the current evidence base is, overall,
limited and not of high quality [43]. Despite this uncertainty consensus indicates that modifiable lifestyle factors (including diet,
and physical and cognitive activity) are addressed when this is clinically appropriate. Generally these aspects of a choosing a healthier
lifestyle are indicated for improved wellbeing for many older
people. Other simple non-pharmacologic interventions, such as
withdrawing medicines with adverse cognitive effects, and ensuring good sleep hygiene are helpful to optimise cognitive function.
Although many studies have evaluated agents that could
potentially promote neuroplasticity or be used as treatments for
nervous system injury, particularly in patients with stroke [42],
pharmacotherapy largely focuses on secondary prevention and
symptomatic interventions. There are also some positive clinical
data regarding the use of aspirin and nimodipine [44,45] in patients
with vascular cognitive impairment. Cholinesterase inhibitors and
memantine have modest effects in treatment of patients with
Alzheimer’s disease, and there are data suggesting that these agents
also have some efficacy in treatment of subjects with vascular or
mixed dementia. Overall the efficacy of these agent appears to be
very modest [46], and may thus not be clinically important for many
patients. Efficacy of rivastigmine for treatment of vascular cognitive
impairment has been systematically reviewed most recently [47].
Three trials (n = 800) were included, but most data were from one
trial (n = 710). In this trial randomisation to rivastigmine therapy
(mean dose 9.4 mg) was associated with a statistically significant
difference of 0.6 points on the mini-mental state examination, as
well as an increase in gastrointestinal adverse events and a doubling
in odds of withdrawal from therapy.
If a parkinsonian gait is present, a trial of dopaminergic therapy is sometimes indicated to determine whether the patient is
dopamine responsive. Parkinsonism due to vascular disease is generally considered to be poorly or non-responsive to L-dopa therapy,
in contrast to idiopathic Parkinson’s disease, which is characteristically dopamine sensitive, at least in the early stages of the disease.
However, some small studies emphasise that a response to L-dopa
is observed in at least some patients with vascular parkinsonism
[48]. Holistic assessment of other falls risk factors, and multifactorial intervention, is usually indicated when an older person
has vascular gait disorder associated with history, or high risk, of
falls.
10. What is the current state of the art?
The search produced 29 clinical trials of which 22 were excluded
because of limited relevance. Additionally, one letter and one protocol paper were excluded (see supplementary material). Included
studies are summarised in Table 1. The included studies are all
observational [49–53]. They highlight that, despite twenty years of
literature regarding the relationship between cerebrovascular and
Alzheimer’s disease, current work continues to try to unravel the
associations between vascular risk factors and amyloid deposition.
11. Conclusion
In the context of increasing longevity, clinicians can expect
to care for increased numbers of older people living with cognitive impairment. Given the intertwined risk factors for the major
causes of cognitive impairment, prevention by control of vascular risk factors, and addressing lifestyle factors is important.
A spectrum of cognitive disorders related to brain vascular disease is recognised and careful clinical assessment is required to
understand the significance of the various contributing factors,
and the importance of imaging findings, for an individual patient.
Treatment interventions, such as recommendations to maintain
cognitive and physical activity, are often based on consensus and
clinical judgement. Although the convergence of risk factors for
C.D. Etherton-Beer / Maturitas 79 (2014) 220–226
vascular and Alzheimer’s disease has received broad attention for
two decades, work continues to try and clarify the pathogenetic
mechanisms underlying these common causes of cognitive impairment. In addition to these gaps in knowledge, treatments with
substantial efficacy that are well tolerated remain elusive.
Contributors
C.E.B. designed the review, extracted the references, drafted and
critically revised the manuscript.
Competing interests
None.
Funding
The author has received no funding for this article.
Provenance and peer review
Commissioned and externally peer reviewed.
Acknowledgements
Swithin Song’s assistance providing Figs. 1 and 2 is gratefully acknowledged. Frederik Barkhof’s permission to reproduce
Fig. 3 (originally published at http://www.radiologyassistant.
nl/en/p43dbf6d16f98d/dementia-role-of-mri.html) is gratefully
acknowledged.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.maturitas.
2014.06.004.
References
[1] Australia’s Health. Australian Institute of Health and Welfare 2010. Australia’s
health series no. 12. Cat. no. AUS 122. Canberra: AIHW; 2010.
[2] Ballard C, McKeith I, O’Brien J, et al. Neuropathological substrates of dementia
and depression in vascular dementia, with a particular focus on cases with
small infarct volumes. Dement Geriatr Cogn Disord 2000;11:59–65.
[3] Makin SD, Turpin S, Dennis MS, Wardlaw JM. Cognitive impairment after
lacunar stroke: systematic review and meta-analysis of incidence, prevalence
and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry
2013;84:893–900.
[4] Piguet O, Ridley L, Grayson DA, et al. Are MRI white matter lesions clinically
significant in the ‘old–old’? Evidence from the Sydney Older Persons Study.
Dement Geriatr Cogn Disord 2003;15:143–50.
[5] Ganguli M, Blacker D, Blazer DG, et al. Classification of neurocognitive disorders
in DSM-5: a work in progress. Am J Geriatr Psychiatry 2011;19:205–10.
[6] O’Brien JT, Erkinjuntti T, Reisberg B, et al. Vascular cognitive impairment. Lancet
Neurol 2003;2:89–98.
[7] Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of
ischemic score in differentiation of dementias. Ann Neurol 1980;7:486–8.
[8] Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.
Neurology 1993;43:250–60.
[9] Wentzel C, Darvesh S, MacKnight C, Shea C, Rockwood K. Inter-rater reliability of the diagnosis of vascular cognitive impairment at a memory clinic.
Neuroepidemiology 2000;19:186–93.
[10] Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Sex, age, cardiovascular risk
factors, and coronary heart disease: a prospective follow-up study of 14,786
middle-aged men and women in Finland. Circulation 1999;99:1165–72.
[11] Knopman D, Boland LL, Mosley T, et al. Cardiovascular risk factors and cognitive
decline in middle-aged adults. Neurology 2001;56:42–8.
[12] Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between
midlife blood pressure levels and late-life cognitive function. The HonoluluAsia Aging Study. JAMA 1995;274:1846–51.
[13] Feigin V. New developments in dementia. Acta Neurol Scand 2003;107:237–8.
225
[14] Casserly I, Topol E. Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet 2004;363:
1139–46.
[15] Blom K, Emmelot-Vonk MH, Koek HL. The influence of vascular risk factors on
cognitive decline in patients with dementia: a systematic review. Maturitas
2013;76:113–7.
[16] Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for
dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–83.
[17] Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective
study of serum total homocysteine concentration and risk of stroke in middleaged British men. Lancet 1995;346:1395–8.
[18] Grammas P. Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflamm
2011;8:26.
[19] Dichgans M, Malik R, Konig IR, et al. Shared genetic susceptibility to ischemic
stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke 2014;45:24–36.
[20] Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds 3rd CF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic
review and meta-analysis of community-based cohort studies. Br J Psychiatry
2013;202:329–35.
[21] Pendlebury ST. Stroke-related dementia: rates, risk factors and implications for
future research. Maturitas 2009;64:165–71.
[22] Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235
causes of death for 20 age groups in 1990 and 2010: a systematic analysis for
the Global Burden of Disease Study 2010. Lancet 2012;380:2095–128.
[23] Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review
of population-based studies of incidence, prevalence, and case-fatality in the
late 20th century. Lancet Neurol 2003;2:43–53.
[24] Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR.
Brain infarction and the clinical expression of Alzheimer disease. The Nun
Study. JAMA 1997;277:813–7.
[25] Longstreth Jr WT, Manolio TA, Arnold A, et al. Clinical correlates of white matter
findings on cranial magnetic resonance imaging of 3301 elderly people. The
Cardiovascular Health Study. Stroke 1996;27:1274–82.
[26] Black S, Gao F, Bilbao J. Understanding white matter disease: imagingpathological correlations in vascular cognitive impairment. Stroke
2009;40:S48–52.
[27] Kim KW, MacFall JR, Payne ME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry 2008;64:273–80.
[28] Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide
to detection and interpretation. Lancet Neurol 2009;8:165–74.
[29] Shenkin SD, Rivers CS, Deary IJ, Starr JM, Wardlaw JM. Maximum (prior) brain
size, not atrophy, correlates with cognition in community-dwelling older people: a cross-sectional neuroimaging study. BMC Geriatr 2009;9:12.
[30] Victoroff J, Mack WJ, Grafton ST, Schreiber SS, Chui HC. A method to improve
interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 1994;44:2267–76.
[31] Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol
1987;149:351–6.
[32] Virdis A, Ghiadoni L, Giannarelli C, Taddei S. Endothelial dysfunction and vascular disease in later life. Maturitas 2010;67:20–4.
[33] Hanon O, Haulon S, Lenoir H, et al. Relationship between arterial stiffness and
cognitive function in elderly subjects with complaints of memory loss. Stroke
2005;36:2193–7.
[34] Barker-Collo S, Starkey N, Lawes CM, Feigin V, Senior H, Parag V. Neuropsychological profiles of 5-year ischemic stroke survivors by Oxfordshire stroke
classification and hemisphere of lesion. Stroke 2012;43:50–5.
[35] Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet
1991;337:1521–6.
[36] Ishii N, Nishihara Y, Imamura T. Why do frontal lobe symptoms predominate
in vascular dementia with lacunes? Neurology 1986;36:340–5.
[37] Thanvi B, Lo N, Robinson T. Vascular parkinsonism – an important cause of
parkinsonism in older people. Age Ageing 2005;34:114–9.
[38] Aarsland D, Sardahaee FS, Anderssen S, Ballard C. Alzheimer’s Society Systematic Review group. Is physical activity a potential preventive factor for vascular
dementia? A systematic review. Aging Ment Health 2010;14:386–95.
[39] Bickel H, Ander KH, Bronner M, et al. Reduction of long-term care dependence
after an 8-year primary care prevention program for stroke and dementia: the
INVADE trial. J Am Heart Assoc 2012;1:e000786.
[40] McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of
dementia. Cochrane Database Syst Rev 2009. CD003160 [online].
[41] McGuinness B, Todd S, Passmore P, Bullock R. Blood pressure lowering in
patients without prior cerebrovascular disease for prevention of cognitive
impairment and dementia. Cochrane Database Syst Rev 2009. CD004034
[online].
[42] Chollet F. Pharmacologic approaches to cerebral aging and neuroplasticity:
insights from the stroke model. Dialogues Clin Neurosci 2013;15:67–76.
[43] Bahar-Fuchs A, Clare L, Woods B. Cognitive training and cognitive rehabilitation
for mild to moderate Alzheimer’s disease and vascular dementia. Cochrane
Database Syst Rev 2013;6. CD003260 [online].
[44] Meyer JS, Rogers RL, McClintic K, Mortel KF, Lotfi J. Randomized clinical trial of
daily aspirin therapy in multi-infarct dementia. A pilot study. J Am Geriatr Soc
1989;37:549–55.
226
C.D. Etherton-Beer / Maturitas 79 (2014) 220–226
[45] Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and
vascular dementia. Cochrane Database Syst Rev 2002. CD000147 [online].
[46] Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase
inhibitors and memantine in vascular dementia: a meta-analysis of randomised
controlled trials. Lancet Neurol 2007;6:782–92.
[47] Birks J, McGuinness B, Craig D. Rivastigmine for vascular cognitive impairment.
Cochrane Database Syst Rev 2013;5. CD004744 [online].
[48] Zijlmans JC, Katzenschlager R, Daniel SE, Lees AJ. The L-dopa response in vascular parkinsonism. J Neurol Neurosurg Psychiatry 2004;75:545–7.
[49] Reed B, Villeneuve S, Mack W, DeCarli C, Chui HC, Jagust W. Associations
between serum cholesterol levels and cerebral amyloidosis. JAMA Neurol
2014;71:195–200.
[50] Nation DA, Edland SD, Bondi MW, et al. Pulse pressure is associated
with Alzheimer biomarkers in cognitively normal older adults. Neurology
2013;81:2024–7.
[51] Haight TJ, Landau SM, Carmichael O, et al. Dissociable effects of Alzheimer
disease and white matter hyperintensities on brain metabolism. JAMA Neurol
2013;70:1039–45.
[52] Zheng L, Vinters HV, Mack WJ, Zarow C, Ellis WG, Chui HC. Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer
pathologic changes. Stroke 2013;44:2835–41.
[53] Weinstein G, Beiser AS, Decarli C, Au R, Wolf PA, Seshadri S. Brain imaging and
cognitive predictors of stroke and Alzheimer disease in the Framingham Heart
Study. Stroke 2013;44:2787–94.
Arbre décisionnel
Notion de maladie d'Alzheimer ou maladie apparentée
CONTEXTE À RISQUE
-
-
Personnel
Pathologie connue
État général altéré
Dépendance
Facteurs de stress
ET/
OU
Environnement
- Changement
- Faible soutien
- Contraintes
Changements de comportement
- Difficultés relationnelles
- Attitudes inhabituelles ou jugées
inadaptées
- Difficultés d’adaptation
Diagnostic positif
Caractérisation symptômes (définition, fréquence, sévérité)
Recherche autres signes (définition, fréquence, sévérité)
Degré d’urgence et de dangerosité
Anamnèse : ancienneté, contexte et période de survenue
Facteurs prédisposants/déclenchants
Confusion
Affection intercurrente,
iatrogénie
Traitement confusion,
affection somatique,
iatrogénie
Recherche pathologie
psychiatrique
décompensée
Traitement cause
psychiatrique
Symptômes
psychologiques et
comportementaux de la
démence
Prise en charge
spécifique
Réévaluation régulière, par plusieurs sources
Neurologie
Mise au point
Octobre 2011
SY NT HÈ SE D’ AVI S DE L A CO MMI SSI O N DE L A T RANS PARE NCE
ARICEPT (donépézil), EXELON (rivastigmine), REMINYL (galantamine),
EBIXA (mémantine),
médicaments du traitement symptomatique de la maladie d’Alzheimer
Un intérêt thérapeutique faible
L’essentiel
Quatre médicaments ont une autorisation de mise sur le marché (AMM) dans le traitement symptomatique
de la maladie d’Alzheimer :
– trois inhibiteurs de l’acétylcholinestérase (IAChE) : ARICEPT (donépézil), REMINYL / REMINYL LP
(galantamine) et EXELON (rivastigmine) ont une AMM dans les formes « légères à modérément sévères »,
– un antagoniste des récepteurs NMDA : EBIXA (mémantine) a une AMM dans les formes « modérées à
sévères ».
Leur efficacité est au mieux modeste et de pertinence clinique discutable. Elle a été démontrée essentiellement sur la cognition et les activités de la vie quotidienne. Aucun impact n’a été démontré sur le délai
d’entrée en institution, la qualité de vie ou la morbi-mortalité.
Ils peuvent entrainer des effets indésirables digestifs, cardiovasculaires et neuropsychiatriques pouvant
nécessiter leur arrêt. Il existe aussi un risque d’interactions médicamenteuses, notamment avec les
psychotropes, souvent co-prescrits.
L’intérêt thérapeutique des médicaments de la maladie d’Alzheimer doit être considéré comme faible. Néanmoins, dans le souci de ne pas priver les patients répondeurs (impossibles à identifier a priori) d’un éventuel bénéfice clinique à court terme, il reste suffisant pour leur prise en charge par la solidarité nationale.
En l’absence de donnée clinique à long terme, l’utilisation de ces médicaments doit faire l’objet d’une réévaluation attentive à un an, au cas par cas. La pertinence de la poursuite du traitement au delà d’un an
ne sera décidée qu’après une réunion de concertation pluridisciplinaire.
Stratégie thérapeutique
En l’absence de donnée clinique solide sur l’effet à long terme de ces médicaments et en raison de l’incertitude sur la
pertinence des effets cliniques et du risque d’effets indésirables graves, leur prescription ne repose que sur des considérations de très faible niveau de preuve.
– Au stade léger de la maladie, on peut utiliser un inhibiteur de l’acétylcholinestérase (IAChE) : donépézil, galantamine
ou rivastigmine.
– Aux stades modéré et modérément sévère, on peut utiliser un IAChE (sans privilégier l’un plutôt qu’un autre). Dans
ces formes, les IAChE représentent une alternative à la prescription de la mémantine.
L’intérêt d’administrer la rivastigmine sous forme de dispositif transdermique par rapport à la voie orale est discutable,
en raison d’un risque de mésusage dont les conséquences peuvent être graves.
– Au stade sévère, seule la mémantine a l’AMM, mais son bénéfice clinique attendu est très limité.
– L’intérêt d’associer deux IAChE ou un IAChE à la mémantine n’est pas démontré.
Au delà de 6 mois de traitement, si le patient a atteint les objectifs fixés (stabilisation ou ralentissement du déclin cognitif par exemple) et en l’absence d’effet indésirable grave et/ou altérant la qualité de vie, le traitement pourra être poursuivi jusqu’à six mois supplémentaires.
Si l’efficacité à 1 an a été maintenue, la poursuite du traitement peut être décidée, en concertation avec l’aidant et, si
possible, avec le patient, à la suite d’une réunion pluridisciplinaire associant médecin traitant, gériatre et neurologue ou
psychiatre, en relation avec le réseau de soins prenant en charge le patient.
La prise en charge nécessite une coordination avec les acteurs sociaux, en particulier avec les aidants familiaux, dont
le rôle est essentiel. Elle exige des compétences spécifiques de la part des soignants, notamment pour réagir face aux
troubles du comportement.
La prescription de psychotropes peut parfois être justifiée, pour une période aussi courte que possible.
Des traitements non médicamenteux (activité physique, stimulation, entrainement cognitif) sont aussi à envisager.
Données cliniques
Les données cliniques ne permettent pas de considérer qu’il existe une différence d’effet entre les IAChE et la mémantine, ni entre les différents IAChE, dans les indications de l’AMM.
Elles montrent une supériorité de ces médicaments par rapport au placebo, principalement documentée sur les troubles cognitifs et les activités de la vie quotidienne, au bout de 6 mois de traitement. La taille d’effet est au mieux modeste et de pertinence clinique discutable.
L’efficacité reste insuffisamment documentée au-delà de 6 mois et n’est pas établie sur les critères cliniques majeurs
(notamment le retard à l’entrée en institution).
Le risque de troubles digestifs (vomissements, diarrhée, hémorragies) parfois graves est établi. Des études pharmacoépidémiologiques ont montré un risque accru de bradycardie, de syncopes, de troubles neuropsychiatriques (léthargie,
hallucinations, dépression, etc.) et d’interactions, en particulier avec les antipsychotiques, souvent co-prescrits.
Conditions particulières de prescription
Médicament soumis à prescription annuelle réservée aux médecins spécialistes en neurologie et en psychiatrie, aux
médecins spécialistes titulaires du diplôme d’études spécialisées complémentaires de gériatrie et aux médecins spécialistes ou qualifiés en médecine générale titulaires de la capacité de gérontologie.
Médicament nécessitant une surveillance particulière pendant le traitement.
Intérêt du médicament
Le service médical rendu* par ces quatre médicaments est faible.
Ils n’apportent pas d’amélioration du service médical rendu** (ASMR V) dans le traitement symptomatique de la maladie d'Alzheimer.
* Le service médical rendu par un médicament (SMR) correspond à son intérêt en fonction notamment de ses performances cliniques et de la
gravité de la maladie traitée. La Commission de la transparence de la HAS évalue le SMR, qui peut être important, modéré, faible, ou insuffisant pour
que le médicament soit pris en charge par la solidarité nationale.
Ce document a été élaboré sur la base des avis de la Commission de la transparence du 19 octobre 2011
(CT-10649, 10676, 10677, 10755), disponibles sur www.has-sante.fr
© Haute Autorité de Santé 2011
** L’amélioration du service médical rendu (ASMR) correspond au progrès thérapeutique apporté par un médicament par rapport aux traitements existants. La Commission de la transparence de la HAS évalue le niveau d’ASMR, cotée de I, majeure, à IV, mineure. Une ASMR de niveau V (équivalent de « pas d’ASMR ») signifie « absence de progrès thérapeutique ».
SYNTHESE DES RECOMMANDATIONS DE BONNE PRATIQUE
Maladie d’Alzheimer et maladies apparentées :
prise en charge des troubles du comportement
perturbateurs
Mai 2009
Ces recommandations portent sur la prise en charge des troubles du comportement jugés par l’entourage
comme dérangeants, perturbateurs, dangereux, que ce soit pour le patient ou pour son entourage. Sont
concernés les comportements perturbateurs suivants : idées délirantes, hallucinations, opposition, agitation,
agressivité, comportements moteurs aberrants, désinhibition, cris, troubles du rythme veille-sommeil.
Les données de la littérature identifiée dans le cadre de ce travail n’ont pas permis de fonder les
recommandations sur des preuves. En conséquence, toutes les recommandations reposent sur un accord
professionnel au sein du groupe de travail, après avis du groupe de lecture.
MESSAGES CLÉS
•
Les troubles du comportement perturbateurs (TCP) ont une origine multifactorielle. Ils peuvent être
déterminés par :
des facteurs écologiques, liés à l’environnement et l’entourage, aux aidants et aux professionnels ;
des facteurs propres à la personne ou à la maladie.
L’enquête doit rechercher en priorité les causes somatiques et psychiatriques, les facteurs déclenchants et les
facteurs prédisposants.
•
Il est recommandé d’utiliser en première intention des techniques de soins non médicamenteuses
appropriées aux TCP.
•
•
Les psychotropes n’ont pas d’effet préventif sur la survenue des TCP.
Un traitement par psychotrope ne doit pas être prescrit sans évaluation préalable en cas d’opposition, de
cris, de déambulations.
Les TCP sont des symptômes différents dans leur nature, mais qui ont des caractéristiques communes :
• ils sont fréquents au cours de ces maladies ;
• ils signalent souvent une rupture par rapport au fonctionnement antérieur du patient ;
• ils sont souvent fluctuants en intensité ou épisodiques ;
• ils sont interdépendants, souvent associés, et interagissant entre eux.
I.
Étiologie et démarche diagnostique
La conduite à tenir recommandée est la suivante :
• apprécier le degré d’urgence, de dangerosité ou de risque fonctionnel à court terme pour le patient
ou pour autrui ;
• interroger et examiner le patient et interroger l’entourage (ancienneté et caractéristiques du
trouble, circonstances de survenue) ;
• rechercher une cause écologique, une cause somatique (rétention d’urine, infection, douleur
aiguë, fécalome, etc.) ou psychiatrique (crise d’angoisse sévère) à traiter en priorité, ainsi que des
facteurs iatrogènes ;
•
•
approfondir l’évaluation clinique des troubles avec leur intensité et leur retentissement ;
répéter cette recherche étiologique à différents moments de la prise en charge si le trouble
persiste.
Il est recommandé d’observer le comportement du patient quand il est seul et en interaction avec les autres
personnes, et à différents moments de la prise en charge.
En cas de troubles persistant depuis plusieurs jours, il est recommandé de les objectiver à l’aide d’un outil tel
que l’inventaire neuropsychiatrique (NPI ou INP). Le NPI est un inventaire de 12 symptômes parmi les plus
fréquents au cours de la maladie d’Alzheimer et des maladies apparentées, qui évalue leur fréquence et leur
sévérité, ainsi que le retentissement sur l’aidant ou le professionnel. Il existe aussi une version courte de
passation plus rapide : le NPI-Réduit, et une version destinée aux équipes soignantes en établissement : le
NPI-ES. Malgré un temps de passation assez long et la nécessité de former les aidants à cet inventaire,
l’usage du NPI est recommandé. Il n’y a pas de consensus sur l’utilisation systématique de cet outil,
notamment en ville. Selon le lieu de vie, les versions suivantes du NPI peuvent être utilisées :
• à domicile : NPI ou NPI-Réduit, renseigné par l’aidant ou un professionnel ;
• en établissement : NPI-ES, renseigné par les soignants.
Il est recommandé d’appliquer les trois principes suivants, quel que soit le lieu de vie :
• un recueil écrit des informations qui doivent être rassemblées dans des fiches ou un dossier pour
faciliter leur traçabilité et leur transmission ;
• il est utile qu’un interlocuteur désigné, éventuellement une personne référente, rassemble ces
informations afin de faciliter leur transmission ;
• les différents professionnels en charge du patient doivent échanger et/ou se rencontrer pour
discuter de ces informations et participer ensemble à l’adaptation de la prise en charge.
II. Prise en charge thérapeutique
Il est recommandé d’utiliser en première intention des techniques de soins non médicamenteuses
appropriées aux TCP. Elles peuvent permettre d’éviter le recours à des traitements médicamenteux.
Les interventions non médicamenteuses sur la qualité de vie, le langage, la cognition, la stimulation
sensorielle, l’activité motrice et les activités occupationnelles n’ont pas apporté la preuve de leur efficacité.
Toutefois, elles peuvent être, tant en ambulatoire qu’en institution, un élément de la prise en charge
thérapeutique globale. Elles peuvent être proposées à titre individuel ou collectif et doivent être pratiquées
par un personnel formé.
Les psychotropes peuvent être utilisés lorsque les techniques de soins sont d’efficacité insuffisante,
notamment quand la sévérité des troubles met en danger le patient, altère son comportement, ou est une
menace ou une source importante de souffrance pour son entourage. Il est recommandé de les utiliser en
synergie avec les techniques de soins. Ils n’ont pas d’effet préventif sur les TCP. Il n’est pas recommandé de
les prescrire en première intention et sans évaluation préalable en cas d’opposition, de cris, de
déambulations.
III. Suivi et prévention des TCP
La prévention des TCP doit reposer sur une stratégie développée et adaptée à chaque patient. Les actions
générales de prévention concernent :
• l’information et le soutien aux aidants naturels ;
• la formation des professionnels ;
• l’environnement du patient, qui doit être le plus adapté possible à son état.
Ce document présente les points essentiels des recommandations de bonne pratique :
« Maladie d’Alzheimer et maladies apparentées : prise en charge des troubles du comportement perturbateurs » Recommandations pour la pratique clinique – Mai 2009
Ces recommandations et l’argumentaire scientifique sont consultables dans leur intégralité
sur www.has-sante.fr
© Haute Autorité de Santé – 2009
Un traitement par psychotrope ne doit pas être instauré si les symptômes sont d’origine somatique ou
iatrogène.