Differentials
Alzheimer disease
SIGNS / SYMPTOMS
The physical exam does not reliably distinguish the conditions, because a normal exam is usually noted. One key feature that may differentiate frontotemporal dementia (FTD) from Alzheimer disease is relative preservation of memory.
INVESTIGATIONS
Structural MRI typically shows regional atrophy in the temporoparietal regions in Alzheimer disease and the temporofrontal regions in FTD; typically medial temporal lobe atrophy in Alzheimer disease, and anterior and inferior temporal lobe atrophy in FTD. CT shows global atrophy in Alzheimer disease, and focal atrophy in FTD.
Amyloid PET/CT shows amyloid retention in the cortex in Alzheimer disease and is positive in more than 86% of patients with Alzheimer disease. It is usually normal in FTD but may be positive in a small proportion of patients with FTD, possibly indicating a mixed pathology.[104]
Single-photon emission computed tomography (SPECT) or PET in early Alzheimer disease generally shows abnormality in the posterior cingulate and parietal lobes.[136]
Cerebrospinal fluid Alzheimer disease biomarkers (e.g., low Aβ42 and high tau, p-tau) can differentiate Alzheimer disease from FTD.[130]
Neurofilament light chain (NfL) levels tend to be higher in FTD than in Alzheimer disease.[137]
Dementia with Lewy bodies (DLB)
SIGNS / SYMPTOMS
DLB is characterized by predominance of amnesia, fluctuation in cognition, visual hallucinations, and parkinsonism in the early stages of the illness.
Personality and comportment are relatively preserved.
Visual hallucinations are very rare in frontotemporal dementia (FTD).[138]
INVESTIGATIONS
MRI/CT shows global atrophy in DLB, and focal atrophy in FTD.
Single photon emission computed tomography (SPECT) or PET in early DLB generally shows abnormality in the parietal and occipital lobes.[136]
Dopamine transporter-SPECT scan can show low dopamine transporter uptake in the basal ganglia in DLB.[139]
Vascular dementia
SIGNS / SYMPTOMS
Vascular dementia may mimic frontotemporal dementia by presenting with prominence of apathy, executive dysfunction, or behavioral disorder (impulsiveness and irritability), and relative preservation of memory.
INVESTIGATIONS
Brain MRI or CT will show evidence of cerebrovascular pathology; lacunes in the basal ganglia and thalamus; or marked gliosis of the frontal, subcortical, and deep white matter.
Bipolar disorder
SIGNS / SYMPTOMS
Episodes of mania and depression typically begin in the third decade of life and show complete remission between episodes. When late-onset mania occurs after age 60 years it is attributable to brain diseases (cerebrovascular, trauma, neoplasm, drug withdrawal and/or intoxication) in >80% of cases.
INVESTIGATIONS
Brain imaging is generally normal in bipolar disorder.
Major depression
SIGNS / SYMPTOMS
Major depression is characterized by the marked predominance of sad mood, anhedonism, hopelessness, suicidal thoughts, psychomotor retardation, insomnia, and self-deprecating and pessimistic mental states. Most likely to be confused with the apathetic type of frontotemporal dementia.
INVESTIGATIONS
Brain imaging is generally normal in major depression.
Obsessive-compulsive disorder (OCD)
SIGNS / SYMPTOMS
Onset of OCD is typically in the second or third decade of life. Remission may not be complete between episodes but OCD can be distinguished by long history and association of compulsions with preserved insight and marked anxiety. Patients with early-onset dementias often try to cope with their cognitive impairment by imposing order on the threat of chaos.
INVESTIGATIONS
Brain imaging is generally normal in OCD.
Substance use disorders
SIGNS / SYMPTOMS
States of intoxication from stimulants, alcohol, and other agents may mimic frontotemporal dementia by producing euphoria, disinhibition, impulsiveness, and poor judgment, but these states are usually transient.
Track marks and puncture sites may be visible on arms, legs, and neck, along the course of superficial veins.
INVESTIGATIONS
Serum and urine toxicology will usually identify the substance involved.
Primary brain tumor
SIGNS / SYMPTOMS
The cognitive manifestations of brain tumor depend on location.
Tumors in the frontal lobes may present with decreased attention and alertness, executive dysfunction, and impaired social judgment.
Tumors in the temporal lobes may present with nonfluent aphasia and memory disorder.
INVESTIGATIONS
Brain imaging will show tumor, and may also show a penumbra of edema and compression of adjacent brain structures.
Hyperthyroidism
SIGNS / SYMPTOMS
Features of hyperthyroidism, such as irritability, restlessness, increased eating (with decreased satiation), and distractibility, may result in a presentation that mimics frontotemporal dementia.
INVESTIGATIONS
Low blood levels of thyroid-stimulating hormone and increased levels of free thyroxine are typical of hyperthyroidism.
Normal pressure hydrocephalus
SIGNS / SYMPTOMS
Features of fronto-subcortical profile with psychomotor slowing and executive function deficits, such as decreased word fluency, may mimic frontotemporal dementia.
INVESTIGATIONS
Brain imaging will show general enlargement of all four ventricles.
HIV dementia
SIGNS / SYMPTOMS
Features such as apathy, behavioral disturbances, and depression may mimic frontotemporal dementia.
INVESTIGATIONS
Serology test is positive for HIV.
Neurosyphilis
SIGNS / SYMPTOMS
Meningismus, fever, and cranial nerve palsies are typical. Rapidly progressive dementia with personality changes that mimic frontotemporal dementia but presence of cranial nerve abnormalities (II, III, IV, VI, VII, and VIII) and uveitis point to syphilis. Psychiatric manifestations may be present.
INVESTIGATIONS
Venereal disease research laboratory tests (blood and cerebrospinal fluid). The fluorescent treponemal antibody-absorbed (FTA-ABS) test has high sensitivity and if negative excludes a diagnosis of neurosyphilis. MRI lesions in temporal lobes disappear with treatment.
Lyme disease
SIGNS / SYMPTOMS
History of exposure to ticks, bullseye rash, fatigue, fever, joint pains, headache, and weight loss. Cognitive decline. The course may be acute or subacute.
INVESTIGATIONS
Raised inflammatory markers, positive serologic tests for Borrelia burgdorferi. Imaging with MRI may help exclude degenerative diseases. Lyme disease responds to antibiotic treatment.
Hepatic encephalopathy
SIGNS / SYMPTOMS
History of liver disease such as hepatitis, exposure to hepatotoxins, such as alcohol. Symptoms of liver failure and its complications, such as jaundice, pruritus, gastrointestinal bleeding, coagulopathy, ascites, renal failure, and changes in mental status which may fluctuate. Signs of advanced chronic liver disease such as muscle wasting, jaundice, ascites, palmar erythema, edema, spider telangiectasias, fetor hepaticus, asterixis.
INVESTIGATIONS
Abnormal liver function tests, coagulation screen, FBC, electrolyte imbalances such as hypokalemia, hyponatremia, uremia, hypoglycemia. CT head may show cerebral edema but no frontotemporal dementia degenerative pattern. Electroencephalography may be helpful.
Use of this content is subject to our disclaimer