Investigations
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Guide de pratique clinique pluridisciplinaire relatif à la collaboration dans la dispense de soins aux personnes âgées démentes résidant à domicile et leurs aidants prochesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2017Multidisciplinaire richtlijn voor thuiswonende oudere personen met dementie en hun mantelzorgersPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 20171st investigations to order
cognitive testing
Test
Tools include the Folstein Mini-Mental State Examination (MMSE), the most commonly used screening test (with high sensitivity for detecting dementia, but which often fails to recognise mild cognitive impairment [MCI]), and the Blessed Dementia Scale.[95][96]
Several other tools are available for bedside screening (e.g., the Saint Louis University Mental Status [SLUMS] examination, and Mini-Cog).[95][97][98][99] Saint Louis University School of Medicine: SLUMS Examination Opens in new window Mini-Cog© Opens in new window
The SLUMS examination has better sensitivity for detecting MCI than the MMSE.[130] The SLUMS examination also accounts for educational background when stratifying cognitive functioning, which will become increasingly important as the sensitivity and specificity of early diagnosis is refined.
Meta-analyses indicate that the Mini-Cog may be a useful cognitive screening tool.[95][97]
Mini-Cog©
Opens in new window However, only a limited number of diagnostic studies using Mini‐Cog are available.[95][97]
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The Montreal Cognitive Assessment (MoCA) test can be used to detect MCI.[100] Montreal Cognitive Assessment Opens in new window
Remote cognitive assessment is increasingly used, but evidence on accuracy is limited and more research is needed.[102]
Result
impaired recall, nominal dysphasia, disorientation (to time, place, and eventually person), constructional dyspraxia, and impaired executive functioning
FBC
Test
Rules out reversible causes of cognitive impairment (e.g., anaemia, infection).
Result
normal
metabolic panel
Test
Hypo- or hypernatraemia, hypo- or hypercalcaemia, and hypo- or hyperglycaemia should be sought to rule out metabolic causes of dementia.
Result
to exclude abnormal sodium, calcium, glucose levels
serum thyroid-stimulating hormone (TSH)
Test
Rule out hyperthyroid- or hypothyroid-associated dementia.
Result
TSH may be low or high
serum vitamin B12
Test
Rule out vitamin B12 deficiency-induced dementia.
Result
may be low
urine drug screen
Test
Rule out recreational drug use.
Result
may be positive
CT brain (without contrast)
Test
Useful in excluding tumours, normal pressure hydrocephalus, subdural haematoma, or vascular disease. In early Alzheimer’s disease, few changes are evident, although hippocampal atrophy, pronounced sulcal/gyral changes, and global atrophy may be evident later in the disease.
Structural imaging is recommended at least once during the work-up.[104][105]
Result
may exclude space-occupying lesions or other pathology
Investigations to consider
cerebrospinal fluid (CSF) analysis
Test
CSF analysis should be considered when clinical features suggest infectious disorders such as HIV, Lyme disease, herpes infection, or prion disease.
Result
may show evidence of infectious aetiology for dementia
serum rapid plasma reagin/Venereal Disease Research Laboratory (VDRL)
Test
Rules out syphilis as a cause of dementia in people at risk.
Result
may be positive
serum HIV testing
Test
Rules out HIV infection as a cause of dementia in people at risk. A fourth-generation combined antigen/antibody immunoassay that detects HIV-1 and HIV-2 antibodies and the HIV-1 p24 antigen is the recommended initial test for people with potential HIV exposure or acquisition.
Result
may be positive
formal neuropsychological testing
Test
Sometimes helpful in differentiating between normal ageing, mild cognitive impairment, and early Alzheimer’s disease, as well as differentiating other neurodegenerative dementias such as dementia with Lewy bodies or frontotemporal dementia.[117]
Batteries include: Wechsler's tests for intellectual functioning; Boston Naming Test for language processing; semantic and category fluency (F-A-S and animal naming); Rey-Osterrieth Complex Figure test for visuo-spatial processing; digit span and reverse/Trail Making Test for attention and memory; Wisconsin card sorting test and trails B for executive functioning.
Result
delayed verbal recall; impaired memory; visuo-spatial abnormalities; difficulties naming objects
genetic testing
Test
Offered for patients with early onset dementia or when a strong family history is present.[118]
Result
chromosome 1, 14, 21 mutations
fluorodeoxyglucose-PET (FDG-PET)
Test
Localises areas of greatest brain involvement.
FDG-PET can distinguish patients with Alzheimer's disease (AD) from people without AD, and shows characteristic reductions of regional glucose metabolic rates in patients with probable and definite AD.[112] It is particularly useful for early diagnosis, as it can show characteristic patterns of AD neurodegeneration earlier than MRI in individuals with mild cognitive impairment who will go on to develop Alzheimer’s dementia. It is also helpful in atypical presentations, when the diagnosis is uncertain and AD is a possibility, and therefore imaging results are likely to impact patient care.[105][113][114][115][116]
Result
decreased glucose uptake in pattern specific to AD
CSF biomarker testing
Test
CSF biomarkers include amyloid beta (ABeta)-1-42, ABeta-1-40, phosphorylated tau (p-tau), and total tau (t-tau).[121] Cochrane reviews concluded that measuring ABeta42 levels in CSF may help differentiate Alzheimer's disease (AD) from other dementia subtypes, but that there is some uncertainty regarding the value of CSF biomarker measurement (t-tau, p‐tau, or p‐tau/ABeta ratio) for identifying which people with mild cognitive impairment will develop AD within a specified period.[122] However, a combination of low ABeta-1-42 and elevated tau or p-tau shows high diagnostic specificity in the context of cognitive changes.[123] Consensus guidelines recommend using CSF biomarkers as an adjunct to clinical evaluation, for predicting functional decline or progression to AD among people with minor cognitive impairment.[124] Appropriate pre- and post-biomarker counselling is required.[124] CSF biomarker testing may be of some benefit in the differential diagnosis of AD and other dementias.[125][126]
Additional potential CSF biomarkers include synaptic proteins such as neurogranin, SNAP-25, and GAP-43.[127]
Result
biomarker testing may show patterns of ABeta and p-tau suggestive of AD
Emerging tests
amyloid-PET
Test
Identifies regions of in vivo amyloid-beta deposition using a radio-ligand superimposed on structural brain imaging. Amyloid imaging with fluorine 18-labelled tracers (18F-florbetapir, 18F-florbetaben, and 18F-flutemetamol) can distinguish people with Alzheimer’s disease (AD) from people without AD, and may be able to identify people with mild cognitive impairment who are at greater risk of developing AD.[105][109][110][111] Can also be helpful in complicated cases to differentiate dementia aetiologies.[133][134]
Currently, amyloid PET imaging is primarily used in the research setting or in the evaluation of unusual presentations, although as new treatments become available, documentation of amyloid status is important in considering treatment eligibility.
Result
evidence of presumably pathological amyloid-beta deposition
blood biomarkers
Test
Potential blood-based biomarkers include the core pathological biomarkers ABeta, total tau (t-tau), and phosphorylated tau (p-tau), and blood markers of neurodegeneration such as neurofilament light chain (NfL).[128][129] Companies have created chemiluminescent immunoassay certified tests that are becoming available and have good correlation with amyloid imaging results.
Result
presence of ABeta, t-tau, p-tau, neurofilament light chain
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