Physical exam and patient history
Because the first symptoms of FTD are sometimes constitutional, identifying the actual date of onset may require some probing. Suggested questions to ask include:
- Has there been a change in personality, creativity, emotional attachment to others, drive, organizational skills or social abilities?
- Has there been a recent weight gain and is overeating a problem?
- Does the patient offend others in public or behave in a disinhibited manner?
These are all symptoms of FTD that you should probe, although determining the exact time when these symptoms started is difficult. An assessment of the patient’s ability to complete activities of daily living helps quantify disease severity. Ask about any family history of neurological or psychiatric disease (relatives may have been misdiagnosed; many patients with genetic forms of FTD are mistaken for other neurological or psychiatric disorders, including Alzheimer’s, Parkinson’s disease or atypical parkinsonian dementias).
Lab tests
You should get a measure of complete blood count, electrolytes, renal, liver and thyroid function and serum B12. All patients diagnosed with FTD should have at least an MRI to look for frontal and anterior temporal atrophy. Other laboratory and imaging tests may be required.
SPECT
HMPAO-SPECT shows bilateral frontal hypoperfusion in early bvFTD and SD, which differentiates FTD from AD, where the hypoperfusion is posterior parietal and temporal.
PET
FDG-PET demonstrates frontal and anterior temporal hypometabolism in patients with FTD/Pick's disease. In patients with SD, FDG-PET shows anterior temporal hypometabolism. In progressive non-fluent aphasia the hypometabolism tends to be in the left fronto-insular region.
PIB-PET measures the presence of beta-amyloid, a protein that accumulates in the brain in AD but not in FTLD. PIB-PET can thus be helpful in distinguishing between AD (elevated PET signal in cortex) and FTLD (no cortical signal is seen).
MRI
On a T1-weighted MRI scan, look for atrophy in the ventromedial frontal cortex, bilateral posterior orbital frontal regions, bilateral insula, anterior cingulate cortex, dorsolateral frontal cortex and premotor cortex to support bvFTD.
SD patients often have severe bilateral, asymmetric anterior temporal atrophy (“knife edge atrophy”) as well as medial temporal atrophy. In SD the amygdala, temporal pole, fusiform and inferolateral temporal gyri are more severely atrophic than in typical AD. Unbiased measurements of T1-weighted MRI scans suggest that atrophy in SD is much more significant in temporal than extra-temporal brain regions.
MRI scans of PNFA patients show atrophy of the left frontal, insular, anterior parietal, perisylvian and superior temporal cortices.
Neuropsychology
Patients with bvFTD tend to show executive function and working memory impairments. Unlike AD, memory and visuospatial skills are relatively spared. Patients may have difficulty with set shifting, concept formation, abstraction and reasoning, inhibition of over-learned responses, response generation, organization, planning, self-monitoring and using feedback to guide behavior.
While bvFTD patients tend to score well on the Mini Mental State Exam (MMSE), SD patients score lower due to their language difficulties. Despite these language problems, episodic memory for recent events is relatively spared. As the disease progresses, SD patients perform progressively worse on category fluency tests (i.e. the number of animals or musical instruments generated in one minute), picture naming (Boston Naming Test) and generating verbal definitions of words and pictures. Many SD patients also have concomitant dyslexia. Nonverbal testing of semantic memory may provide better results.
Like patients with bvFTD, PNFA patients tend to show executive function and working memory deficits while episodic memory, semantic memory and visuospatial function are preserved. Unlike bvFTD, PNFA causes specific language difficulties including agrammatism, phonemic paraphasias, anomia, stuttering, impaired repetition, apraxia of speech, alexia and agraphia.