With the exception of occasional genetic causes, today there is no single test that can diagnose FTD with certainty. The diagnosis of FTD requires a thorough history, verified by a caregiver, and a neurological examination.
As with other degenerative diseases, FTD presents an insidious onset and progresses over time. When the diagnosis is uncertain, referral to a neurologist with an interest in cognition and behavior and/or a geriatric neuropsychologist is indicated.
All patients should be screened for obstructive sleep apnea (OSA), as executive dysfunction and behavior changes are common in OSA. If the classic features of OSA are present (e.g., loud disruptive snoring, snorts and apneic pauses while sleeping, crowded oropharynx, excessive daytime sleepiness, repetitive desaturations on overnight oximetry), then referral to a sleep medicine specialist and polysomnography is indicated.
Blood work should be done to exclude alternative causes of cognitive symptoms, including a basic metabolic panel, CBC, RPR, ESR, B12 level and thyroid studies. Vascular risk factors should be assessed. Infections (including HIV), immune-based dementias and neoplastic/paraneoplastic etiologies are occasionally causative or significant contributors, and should be considered.
When a family history is positive, genetic testing of the diagnosed patient can be undertaken. It is recommended that the individual see a genetic counselor first, to be sure they understand the implications of this testing. Patients and their families can be pointed to AFTD’s page on the Genetics of FTD for more information.
A full neuropsychological testing evaluation should be used to better assess the pattern of cognitive loss in an individual suspected of having FTD and to help rule out psychiatric etiologies for an individual’s symptoms. Screening neuropsychological testing takes several hours and is done by a neuropsychologist (or sometimes under direction of a neuropsychology technician). It provides additional supportive evidence for the FTD diagnosis, keeping in mind that some patients perform within normal limits when features are mild. When PPA is suspected, a comprehensive evaluation by a speech/language pathologist is warranted.
Brain imaging is indicated in all individuals with symptoms of FTD to rule out structural causes. MRI scanning will identify small vessel ischemia, subdural hematomas, strategically placed tumors and hydrocephalus. Additionally, the pattern of brain atrophy can support the diagnosis. Severe “knife-edge atrophy” of the frontal and/or anterior temporal lobes may be seen. Often this is asymmetrical. There is often relative sparing of the posterior head regions. However, new research indicates that atrophy of the parietal lobe is found in many genetic cases.
The MRI is more sensitive for assessing vascular changes and subtle patterns of atrophy, but it requires an individual to lie still for 15 to 30 minutes. If the individual is unable to tolerate this, or if they are severely claustrophobic, a CT scan may be more realistic. If the MRI or CT scan does not show atrophy, and the diagnosis remains unclear, a fluorodeoxyglucose positron emission tomography (FDG-PET) scan or SPECT (single proton emission CT) scan may be considered. FDG-PET scans are more specific, but are costly. They show functional changes in brain glucose metabolism, and are often positive earlier than MRIs. The SPECT scan is less costly, but it reflects blood flow more than metabolic change, and is felt to be less sensitive for FTD.
The FDA has approved 3 different versions of a PET tracer for amyloid – currently valuable to FTD diagnosis as a negative scan ruling out Alzheimer’s disease.
Lumbar puncture is another test that can be used to rule out mimicking conditions (infection, immune etiologies, carcinomatous and paraneoplastic syndromes). Measurement of CSF phospho-tau, total tau and Beta-amyloid can sometimes support the diagnosis of FTD over Alzheimer’s disease. As this is an invasive procedure, the value of additional information to be gained should be discussed with patient and family.
Electrophysiologic testing is sometimes warranted in patients with possible FTD. The pattern of change in electroencephalography is nonspecific in FTD; often the test is normal. It may be used to rule out nonepileptic seizures and other systemic (hyperammonemia) or infectious (prion) disorders. Although nonspecific, this testing is easily obtained at many hospitals, is less costly, and it is relatively noninvasive. Electromyography is uncomfortable, but may be indicated in cases where concurrent motor neuron disease is suspected.
The Role of Specialists
Many primary care physicians are uncomfortable making the diagnosis of FTD. Given the uncommon nature of the condition, and the implications of an incorrect diagnosis, it is reasonable to refer those suspected of having FTD to a specialty center in cognitive disorders. Most of these are directed by neurologists, though an interested geriatric psychiatrist or geriatrician may also be appropriate. Psychiatrists are helpful when behavioral or emotional problems are predominant. Geriatricians are desirable in older FTD patients with concurrent medical comorbidities.
Some individuals seek rehabilitation services. These are appropriate when there are functional disabilities in communication (speech therapy), mobility (physical therapy) or self-care (occupational therapy). Cognitive therapies are sometimes appropriate when specific tasks need to be learned. A referral for behavioral management strategies can also be helpful for caregivers since most individuals with FTD are more functional in a structured, consistent environment.
There are no medications which are FDA-approved for the management of FTD-related features. In some instances, such as when behavioral dyscontrol or marked irritability is present, medications can decrease these features. Management of problematic FTD features is challenging, and establishing a working relationship between a primary care physician and a cognitive/behavioral neurologist or psychiatrist, along with a neuropsychologist with expertise in non-pharmacologic modes of behavior management, is strongly advised.
Importance of Pathology
A definitive diagnosis of FTD can only be made post-mortem via autopsy of the brain. Confirmation of diagnosis is important for families, and in the advancement of research. Autopsy evaluation of a patient with FTD can be daunting to a general pathologist. Bigio (see below) provides a step-wise histochemical and immunohistochemical approach to investigation for the general pathologist conducting an autopsy on a decedent with FTD.
- Diagnosing FTD
- Chow TW and Alobaidy A. Incorporating new diagnostic schemas, genetics, and proteinopathy into the evaluation of frontotemporal degeneration. April 2013. Dementia Issue, American Academy of Neurology Continuum Series.
- Manoochehri M, Huey ED. Diagnosis and management of behavioral issues in frontotemporal dementia. Curr Neurol Neurosci Rep. 2012 Oct;12(5):528-36
- Whitwell JL, Josephs KA. Recent advances in the imaging of frontotemporal dementia. Curr Neurol Neurosci Rep. 2012 Dec;12 (6):715-23.
- Criteria for Behavioral Variant FTD (2011).
- FTD Genetics and Genetic Counseling
- Goldman JS, Rademakers R, Huey ED, et al. An algorithm for genetic testing of frontotemporal lobar degeneration. Neurology. 2011 Feb 1: 76(5); 475-83.
- Goldman JS. New approaches to genetic counseling and testing for Alzheimer’s disease and frontotemporal degeneration. Curr Neurol Neurosci Rep. 2012 Oct;12(5):502-10.
- Bigio EH. Making the diagnosis of frontotemporal lobar degeneration. Arch Pathol Lab Med. 2013 Mar; 137(3):314-25.
- New England Journal of Medicine – FTD Clinicopathological Conference
- Two members of AFTD’s Medical Advisory Council – Bradford C. Dickerson, M.D. and Bruce Miller, M.D. – presented a Clinicopathological Conference at Massachusetts General Hospital to demonstrate a differential diagnostic process in neurodegenerative disease. Case 9-2015 – A 31-Year-Old Man with Personality Changes and Progressive Neurologic Decline, was published in the New England Journal of Medicine on March 19, 2015. This case can be used as an educational tool with colleagues and students to demonstrate when a diagnosis of FTD should be considered.
- Handb Clin Neurol. 2016;136:971-84. doi: 10.1016/B978-0-444-53486-6.00050-8.
- Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice.
- Frontotemporal Dementias
- Diagnostic criteria
- bvFTD – Rascovsky, K, Hodges, JR, Knopman, D, Mendez, MF, et al. Sensitivity of revised diagnostic criteria for the behaviourial variant of frontotemporal dementia. Brain 2011 Sept; 134:2456 – 2477.
- PPA – Gorno-Tempini, ML, Hillis, AE, Weintraub, S, Kertesz, A. Classification of primary progressive aphasia and its variants. Neurology 2011 March 15; 76: 1006 – 1014.
- PSP – Höglinger, GU, Respondek, G, Stamelou, M, Kurz, C, et al. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Movement Disorders 2017 Jun; 32: 853-864.
- CBD – Armstrong, MJ, Litvan, I, Lang, AE, Bak, TH, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: 496 – 503.
- FTD-ALS – Strong, MJ, Abrahams, S, Goldstein, LH, Wooley, S, et al. Amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2017 Jun 12; 18: 153-174.