Investigations

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational guidance:

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: 2017

1st investigations to order

cognitive testing

Test
Result
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] [ Cochrane Clinical Answers logo ] ​​​​

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
Result
Test

Rules out reversible causes of cognitive impairment (e.g., anaemia, infection).

Result

normal

metabolic panel

Test
Result
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
Result
Test

Rule out hyperthyroid- or hypothyroid-associated dementia.

Result

TSH may be low or high

serum vitamin B12

Test
Result
Test

Rule out vitamin B12 deficiency-induced dementia.

Result

may be low

urine drug screen

Test
Result
Test

Rule out recreational drug use.

Result

may be positive

CT brain (without contrast)

Test
Result
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

MRI brain (without contrast)

Test
Result
Test

Increased sensitivity in identifying lesions compared with CT findings.[131][132]​ Structural imaging is recommended at least once during the work-up.[104][105]

Result

generalised atrophy with medial temporal lobe and later parietal predominance

Investigations to consider

cerebrospinal fluid (CSF) analysis

Test
Result
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
Result
Test

Rules out syphilis as a cause of dementia in people at risk.

Result

may be positive

serum HIV testing

Test
Result
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
Result
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
Result
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
Result
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
Result
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
Result
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
Result
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

Use of this content is subject to our disclaimer