The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Points) are defined at the end of the "Major Recommendations" field.
Diagnostic Evaluation
Medical History
The clinical history should be supplemented by an independent informant where available (Level A).
Neurological and Physical Examination
A general neurological and physical examination should be performed on all patients presenting with dementia (Good Practice Point).
Assessment of Cognitive Functions
Cognitive assessment is central to diagnosis and management of dementias and should be performed in all patients (Level A). Quantitative neuropsychological testing, ideally performed by someone trained in neuropsychology, should be considered in patients with questionable, prodromal, mild, or moderate dementia (Level C). The specialist physician should include a global cognitive measure and in addition more detailed testing of the main cognitive domains including memory, executive functions and instrumental functions (Level C).
Assessment of Behavioural and Psychological Symptoms
Assessment of behavioural and psychological symptoms of dementia is essential for both diagnosis and management, and should be performed in all patients (Level A). Symptoms should be actively enquired about from the patient and a closely involved carer using appropriate rating scales (Good Practice Point). Co-morbidity should always be considered as a possible cause (Level C).
Assessment of Activities of Daily Living
Impairment of activities of daily living due to cognitive impairment is an essential part of the criteria for dementia and should be assessed in the diagnostic evaluation (Level A). A semi-structured interview from the caregiver is the most practical way to obtain relevant information, and a panel of validated scales is available (Good Practice Point).
Assessment of Co-Morbidity
Assessment of co-morbidity is important in the evaluation of the patient with dementia, and should be performed not only at the time of diagnosis, but throughout the course of the disease, with particular attention to episodes of sudden worsening of cognitive or behavioural symptoms (Good Practice Point).
Blood Tests
The following blood tests are generally proposed as mandatory tests for all patients at first evaluation, both as a potential cause of cognitive impairment or as co-morbidity: blood sedimentation rate, complete blood cell count, electrolytes, calcium, glucose, renal and liver function tests, and thyroid stimulating hormone. More extensive tests will often be required, (e.g., vitamin B12 and serological tests for syphilis, human immunodeficiency virus [HIV], and Borrelia, in individual cases) (Good Practice Point).
Neuroimaging
Structural imaging should be used in the evaluation of every patient suspected of dementia: Non-contrast computed tomography (CT) can be used to identify surgically treatable lesions and vascular disease (Level A). To increase specificity, magnetic resonance imaging (MRI) (with a protocol including T1, T2 and FLAIR sequences) should be used (Level A). Single photon emission computed tomography (SPECT) and positron emission tomography (PET) may be useful in those cases where diagnostic uncertainty remains after clinical and structural imaging work up, and should not be used as the only imaging measure (Level B).
Electroencephalography (EEG)
The EEG may be a useful adjunct, and should be included in the diagnostic work up of patients suspected of having Creutzfeldt-Jakob disease or transient epileptic amnesia (Level B).
Cerebrospinal Fluid (CSF)
CSF analysis with routine cell count, protein, glucose, and protein electrophoresis is recommended in patients with a clinical suspicion of certain diseases and in patients with atypical clinical presentations (Good Practice Point). CSF total tau, phospho-tau, and Ab42 can be used as an adjunct in cases of diagnostic doubt (Level B). For the identification of Creutzfeldt-Jakob disease (CJD) in cases with rapidly progressive dementia, assessment of the 14-3-3 protein is recommended (Level B).
Genetic Testing
Screening for known pathogenic mutations can be undertaken in patients with appropriate phenotype or a family history of an autosomal dominant dementia. This should only be undertaken in specialist centres with appropriate counselling of the patient and family caregivers, and with consent (Good Practice Point).
Pre-symptomatic testing may be performed in adults where there is a clear family history, and when there is a known mutation in an affected individual to ensure that a negative result is clinically significant. It is recommended that the Huntington's disease protocol is followed (Good Practice Point).
Routine Apo E genotyping is not recommended (Level B).
Tissue Biopsy
Tissue biopsy can provide a specific diagnosis of some rare dementias. This should only be undertaken in specialist centres in carefully selected cases (Good Practice Point).
Disclosure of Diagnosis
Disclosure of diagnosis should be done tactfully and should be accompanied by information about the consequences and the progression of the disease, as well as useful contacts such as the local or national Alzheimer's association. In countries where this is possible physicians may also wish to encourage patients to draw up advance directives containing future treatment and care preferences (Good Practice Point).
Management of Alzheimer's Disease (AD) and Other Disorders Associated with Dementia
Treatment of Alzheimer's Disease
In patients with AD, treatment with cholinesterase inhibitors (ChEIs, donepezil, galantamine, or rivastigmine) should be considered at the time of diagnosis, taking into account expected therapeutic benefits and potential safety issues (Level A). Realistic expectations for treatment effects and potential side effects should be discussed with the patient and caregivers (Good Practice Point).
In patients with moderate to severe AD, treatment with memantine can be considered, alone or in combination with a ChEI, taking into account expected therapeutic benefits and potential safety issues (Level A). Realistic expectations for treatment effects and potential side effects should be discussed with the patient and caregivers (Good Practice Point).
Currently, there is insufficient evidence to consider the use of gingko biloba, anti-inflammatory drugs, nootropics, selegiline, oestrogens, vitamin E or statins in the treatment or prevention of AD (Level A–C).
Treatment of Vascular Dementia (VaD)
ChEIs (currently evidence exists for donepezil) may be considered in patients fulfilling diagnostic criteria for VaD of mild to moderate severity (Level B). Realistic expectations for treatment effects and potential side effects should be discussed with the patient and caregivers (Good Practice Point). In the presence of severe focal neurological deficits, the accuracy of diagnosis and expected therapeutic benefits should be carefully considered based on the presumed contribution of sensory-motor impairment versus cognitive deficits to the overall disability of the patient (Good Practice Point).
There is insufficient evidence to consider the use of memantine in patients with vascular dementia (Level B).
There is insufficient evidence to support the use of aspirin, gingko biloba, calcium antagonists or pentoxifylline in the treatment of VaD (Level A–C).
Optimum management of vascular risk factors, including anti-platelet drugs, should be ensured, not only in vascular dementia, but also in patients with other dementias or co-morbid vascular disease (Good Practice Point).
Treatment of Parkinson Disease Dementia (PD-D) and Dementia with Lewy Bodies (DLB)
Treatment with ChEIs (currently evidence exists for rivastigmine) can be considered in patients with PD-D or DLB (Level A), taking in account expected therapeutic benefits and potential safety issues. Realistic expectations for treatment effects and potential side effects should be discussed with the patient and caregivers (Good Practice Point).
There is insufficient evidence for the use of memantine in PD-D or DLB (Level C).
Monitoring Treatment with ChEIs and Memantine
Efficacy and side effects should be regularly monitored during treatment (Good Practice Point). In case of rapid worsening or an apparent loss of efficacy discontinuation of treatment may be considered on a trial basis. Such patients should be closely monitored in order to assess withdrawal effects or worsening in which case the treatment should be re-started (Level C).
Treatment of Other Dementia Disorders
There are no drugs available for the specific treatment of other degenerative dementias such as fronto-temporal dementia (FTD), progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD) (Level C). A number of pathological conditions and systemic or central nervous system disorders can be associated with dementia. Their specific treatment must be based on the underlying etiology (Good Practice Point).
Treatment of Behavioural and Psychological Symptoms in Dementia
Clinicians treating patients with dementia should be aware of the importance of treating behavioural and psychiatric symptoms and the potential benefits for patient and carer (Good Practice Point). Somatic co-morbidity should be considered as the cause of the symptoms (Level C). Non-pharmacological and then pharmacological interventions for behavioural and psychological symptoms of dementia (BPSD) may both be effective and should be applied in a targeted symptom approach. The short, medium and long term benefits and adverse effects of such interventions should be regularly reviewed (Level C). Antipsychotics, conventional as well as atypical, may be associated with significant side effects and should be used with caution (Level A).
Counselling and Support for Caregivers
A dementia diagnosis mandates an inquiry to the community for available public health care support programs (Good Practice Point). Specialist physicians should assess caregiver distress and needs at regular intervals throughout the course of the disease (Level C). Caregivers should be offered support and counselling (Level B). This includes information about patient organizations (Good Practice Point).
Legal Issues
Specialist physicians responsible for the care of patients with dementia should be aware of national legislations relating to assessment of capacity, consent to treatment and research, disclosure of diagnosis, and advance directives (Good Practice Point).
A diagnosis of dementia is not synonymous with mental incapacity, as a determination of capacity should always involve a 'functional' analysis: does the person possess the skills and abilities to perform a specific act in its specific context? (Good Practice Point).
Driving
Assessment of driving ability should be done after diagnosis and be guided by current cognitive function, and by a history of accidents or errors whilst driving. Particular attention should be paid to visuospatial, visuoperceptual, praxis and frontal lobe functions together with attention. Advice either to allow driving, but to review after an interval, to cease driving, or to refer for retesting should be given (Level A). This decision must accord with the national regulations of which the specialist physician must be aware (Good Practice Point).
Conclusion
The assessment, interpretation, and treatment of symptoms, disability, needs, and caregiver stress during the course of AD and other dementia disorders require the contribution of many different professional skills. Ideally, the appropriate care and management of patients with dementia requires a multidisciplinary and multi-agency approach. Neurologists should be involved together with old age psychiatrists and geriatricians in the development and leadership of multidisciplinary teams responsible for clinical practice and research in dementia. This review contributes to the definition of standards of care in dementia by providing evidence for important aspects of the diagnosis and management of dementia.
Definitions:
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations for a Diagnostic Measure
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Points Where there was a lack of evidence but consensus was clear, the Task Force has stated their opinion as good practice points.
