Tests
1st tests to order
formal cognitive testing
Test
Cognitive test performance should be recorded at initial assessment and then every 6 months.
The mini-mental state examination (MMSE) remains the most widely used (and best understood) simple cognitive test. However, patients with FTD can score above the cut-off score of 24/30 even if they have significant cognitive impairment, so it is of limited usefulness for detecting FTD. The Montreal cognitive assessment (MOCA) can be used to assess for decline in cognition over time.[62]
The frontal assessment battery, a bedside test that can be administered in 10 minutes, is helpful for screening and identifying frontal lobe dysfunction.[63]
The Executive Interview (EXIT) is another useful bedside screening tool for detecting possible frontal lobe dysfunction. It comprises a short screen of 25 items, and takes approximately 15 minutes.[64] The Quick EXIT is an abridged, 14-item version of the original EXIT.[65]
Poor emotional processing is detectable in patients with all 3 FTD subtypes, and is an important clinical feature in behavioral variant FTD and semantic dementia.[66] Emotional responses often confound interpretation of cognitive test results, so careful longitudinal evaluations are needed to support diagnosis.
The frontotemporal rating scale (FRS) was developed specifically for FTD, and can detect functional deterioration over 12 months.[68] The degree of dementia severity is more accurately estimated by the FRS than by conventional dementia rating scales.
Result
disproportionately poor performance in test-taking behavior and/or in tests of executive functioning; poor emotional processing; MMSE score often in normal range; in MOCA, frontal subsets may show abnormality
brain MRI
Test
MRI should be ordered whenever a diagnosis of FTD is suspected. If the result is normal or indeterminate, fluorodeoxyglucose-PET can be used.[76]
Result
focal atrophy in the frontal and/or anterior temporal lobes; frequently the atrophy is characterized by left-right asymmetry
brain CT
Test
CT should be ordered if a diagnosis of FTD is suspected but MRI is not available or is contraindicated. If the result is normal or indeterminate, fluorodeoxyglucose-PET can be used.[76]
Result
focal atrophy in the frontal and/or anterior temporal lobes; frequently the atrophy is characterized by left-right asymmetry
CBC
Test
Ordered to rule out anemia.
Result
usually normal
serum CRP
Test
Ordered to screen for inflammatory conditions.
Result
usually normal
serum thyroid-stimulating hormone (TSH)
Test
Ordered to rule out hyperthyroidism. TSH is low in hyperthyroidism.
Result
usually normal
free thyroxine (T4)
Test
Ordered to rule out hyperthyroidism. Free T4 is elevated in hyperthyroidism.
Result
usually normal
metabolic panel
Test
Ordered to exclude abnormal sodium, calcium, and glucose levels.
Result
usually normal
serum BUN
Test
Ordered to rule out renal failure as a cause of cognitive decline.
Result
usually normal
serum creatinine
Test
Ordered to rule out renal failure as a cause of cognitive decline.
Result
usually normal
LFTs
Test
Ordered to rule out liver failure as a cause of cognitive decline.
Result
usually normal
serum vitamin B12 levels
Test
Ordered to rule out cognitive decline secondary to megaloblastic/pernicious anemia.
Result
usually normal
serum folate levels
Test
Ordered to rule out cognitive decline due to folate deficiency.
Result
usually normal
syphilis serology
Test
May be positive in syphilis.
Result
usually normal
HIV testing
Test
Positive in dementia in HIV.
Result
usually normal
serum enzyme-linked immunosorbent assay
Test
May be positive for antibodies to Borrelia burgdorferi in Lyme disease.
Result
usually normal
Tests to consider
brain fluorodeoxyglucose (FDG)-PET
Test
Should be ordered if MRI or CT result is normal or indeterminate. If the FDG-PET result is indeterminate, may consider SPECT.
FDG-PET imaging is also indicated in the assessment of progressive dementia and of neurodegeneration in patients with mild cognitive impairment.[76]
Result
focal hypometabolism in the frontal and/or anterior temporal lobes; frequently asymmetric
brain single-photon emission computed tomography (SPECT)
Test
SPECT may be ordered if result from FDG-PET is normal or indeterminate.[76]
Result
focal hypoperfusion in the frontal and/or anterior temporal lobes; frequently asymmetric
brain biopsy
Test
Neuropathologic exam is the standard for definitive diagnosis. Specimens may be obtained by brain biopsy, but this is generally not recommended. Therefore, pathologic confirmation is typically obtained at the end of life, and is particularly valuable in the characterization of familial dementia.
Result
on gross exam, regional atrophy predominantly affecting the frontal and/or temporal lobes is found; molecular neuropathology allows most cases of FTD to be placed into one of three molecular subgroups: frontotemporal lobar degeneration with tau (30% to 50% of cases), TDP-43, or FET protein accumulation
genetic testing
Test
Family history of FTD is a good indicator of whether genetic testing is appropriate. Mutations in the GRN and MAPT genes are present almost exclusively in patients with a strong family history, whereas C9orf72 expansion can occur in apparently sporadic disease. Genetic testing is desirable for all patients with probable or possible behavioral variant FTD (bvFTD), and in patients with suspected bvFTD with strong psychiatric features and at least one affected family member. Screening for C9orf72 mutations should take place for all patients with suspected FTD with prominent psychiatric symptoms or family history of late-onset primary psychiatric disorder (even if full diagnostic criteria are not met).[24] Genetic testing should be considered within the context of a clinical genetic service with the capacity to provide educational and psychological support for affected families.
Result
demonstration of mutations in the MAPT, GRN, or C9orf72 genes typically; mutations in CHMP2B and other genes are rare; analysis may identify a gene pertinent to a different dementia (such as Alzheimer disease), in which circumstance the case is an FTD phenocopy
connective tissue panel
Test
Ordered if indicated; positive results may rule out FTD.
Result
usually normal
serum erythrocyte sedimentation rate
Test
Ordered to screen for inflammatory conditions.
Result
usually normal
Emerging tests
cerebrospinal fluid analysis
Test
Cerebrospinal fluid (CSF) markers may be of some diagnostic value. A marked elevation of neurofilament light chain (NfL) protein may be Indicative of FTD.[69][70] Higher levels of NfL or amyloid (Aβ42/Aβ38 and Aβ42/Aβ40), and lower levels of amyloid precursor protein (sAPPβ), in CSF may help to distinguish FTD from Alzheimer disease.[71] Neuronal pentraxin 2 (NPTX2) in CSF is reduced in a genetic variant of FTD; decreases in NPTX2 levels probably reflect synaptic dysfunction or loss.[72]
Result
elevation of NfL or amyloid (Aβ42/Aβ38 and Aβ42/Aβ40); decreases in levels of sAPPβ or NPTX2
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