Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that selectively attacks the frontal and anterior temporal regions of the brain. Typical age of onset is between 50 and 60 years, although FTLD can occur as early as the 20’s. The prevalence of FTLD between the ages 45-70 approaches that of Alzheimer’s disease.

Genetics remains the only risk factor for FTLD. The majority of cases are sporatic, but 10% of the cases follow an autosomal dominant pattern of inheritance. (Chow et al., 1999; Stevens et al., 1998)

There are several sub types of FTLD; Behavioral variant FTD, features are early decline in social and personal conduct, emotional blunting, and loss of insight. There is a shift from warmness to coldness. Change in religious or political beliefs are common (Miller et al., 2001). Respect for personal boundaries disappear, and some patients stare or become over friendly talking openly to strangers (including children) (Miller et al., 2001) Increased trust in others makes most patients vulnerable to financial scams or sexual exploitation.

Indiscretion causes embarrassment to the family, and disinhibited verbal outbursts or socially inappropriate behaviors are common. (Mendez, Perryman, Miller, Swartz & Cummings, 1997; Mendez, Solwood, Mastri & Frey, 1993). Antisocial behaviors, including crimes develop de novo, and often reflect poor judgement and impaired impulse control (Miller et al., 1997). Shoplifting, sexual exhibitionism, speeding and running stop signs are common, but well planned criminal activities are rare in these patients. (Cummings & Duchen, 1981; Miller, Darby, Swartz, Yener & Mena, 1995). Episodic memory deficits can be prominent, leading to a misdiagnosis of Alzheimer’s disease.

Nonfluent Progressive Aphasia (NFPA)

NFPA is indicated by problems with speech and language problems. Patients have effortful, hesitant and broken speech and the number of words and phrases diminishes. Reading, writing and confrontation naming are also impaired. As the disease progresses, the speech becomes less fluent and naming and repetition declines. Comprehension of single words eventually fails. Ultimately, patients with NFPA become mute (Bak, O’Donovan, Xureb, Boniface & Hodges, 2001). Although apathy, depression, and social withdrawal are common, other behavioral abnormalities seen in FTD are not typical in the early NFPA. As the disease progresses, similar behavior problems may develop when the degeneration spreads to the right side of the brain.

Semantic Dementia (SD)

SD patients show impairment of word meaning and object identity, and exhibit fluent empty, spontaneous speech (Hodges, Patterson, Oxbury & Funnell, 1992; Snowden, 1999). SD is not simply a language deficit but represents a fundamental loss of semantic memory and knowledge; long term memories that contain an understanding of their relationship (Murre, Graham, & Hodges, 2001).  Facts, concepts and words disappear; as do autobiographical items. (Westmacott, Leach, Freedman, & Moscovitch, 2001) In contrast to Alzheimer’s disease, often orientation and day to day memory remains intact. Patients with SD are more impaired in the recall of distant life events than recent ones (Graham, Becker, & Hodges, 1997). This pattern of memory loss contrasts dramatically with that in AD, in which more remote events tend to be spared.

Behavioral and emotional disorders are also noted in SD, but differ from those in FTD. Depression, loss of empathy, fatigue, and intensification of beliefs are common first symptoms in patients with right-sided damage. Hence, these are easily diagnosed as having disorders that are psychiatric in origin. As the right temporal lobe progressively degenerates, deficits in recognition of negative emotions commonly contribute to loss of empathy (Snowden and his colleagues, 2001).

FTD-Motor Neuron Disease (FTD-MND)

There is a great overlap between FTD and ALS (Amyotrophic lateral sclerosis, or Lou Gehrig’s Disease). Recent works from the University of California, San Francisco suggest that FTD with ALS may be the most strongly genetic of all FTLD subtypes (Holser, et al.; 2000). The illness begins with changes in personality or behavior, impaired insight, apathy euphoria, and disinhibition or irritability. Some classic behavioral alternations of FTD, such as pacing, collecting or operating can be masked by the motor neuron disorder.

Corticobasal disorder (CBD) & Progressive Supranuclear Palsy (PSP)

PSP and CBD are closely related, atypical, parkensonian neurodegenerative disorders with prominent involvement of the frontal cortex. The disorders present usually around 60 years of age with average disease survival of approximately 5-6 years. PSP is characterized by early postural instability and falls, bilateral parkensonian involvement, oculomotor signs, and rapid disease progression (Litvan, 1998, 2004). Apathy is prevalent in PSP patients and may be treated unsuccessfully for depression. Patients may characterize their limb “as having a mind of its own”. Other frequent motor symptoms are mirror movements (involuntary movements of the opposite limb imitating movements in examined limb) and tremor. Walking gate is wide based and unsteady. Speech is spastic and hypokinetic. Supranuclear vertical gaze is key feature in diagnosing PSP, however it may not be present until 3 to 4 years after symptom onset (Hattori et al., 2003). In addition, blink rate is profoundly diminished in PSP. There is characteristic staring facial expression in PSP.

CBD on the other hand, balance disturbances appear later than in PSP as asymmetrical parkensonism, presenting with a slowly progressive, jerky, tremulous, rigid limb, held in a fixed position, and eventually display an alien limb syndrome. Oculomotor apraxia, the absence of controlled, voluntary, and purposeful eye movement is present in patients with CBD.

Source: The Human Frontal Lobes, Miller and Cummings, Second Edition

ABC’S OF FTD

Source: University of California, San Francisco, Department of Neurology, Memory and Aging Center

A – Affect (Mood)

Depression
Apathy
Manic
Anxiety

B – Behavior

Delusions/hallucinations
Agitation
Aggression
Dis-inhibition (sexual, social)
Inflexibility
Hyperorality

C – Cognition

Loss of Abstract Reasoning
Loss of Insight
Loss of Judgement
Memory Loss
Visuospatial Dysfunction (getting lost)
Problems with ADLs (Activities of Daily Living: dressing, eating, bathing, taking medications, operating microwaves, remote controls, etc).

ABCs of FTD by Paul E. Schulz, M.D.

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Possible Symptoms

Note: Not every FTLD sufferer will exhibit all the following symptoms. This is meant to serve only as a guideline.

Early Stage

Depression
Compulsive behaviors
Slight mood changes
Difficulty doing math in head
Difficulty focusing
Difficulty finding words
Stopping in mid-sentence

Middle Stage

More reclusive, paranoid
Communicates less
Smiles less
More conscious about spending money
Stops reading
Stops favorite activities
Speech harder to understand
Problems with work
More aggressive behaviors
More sexually active
Fewer friends
Inappropriate behavior
Rigid behaviors
Artistic abilities may change

Late Stage

Repeats familiar phrases
Flips words around
Rarely smiles, joyless
Craves sweets
Stops cooking
More paranoid
Not able to handle social situations
Little concern about personal hygiene
Repetitive behaviors
Rapid mood changes
Failure to show concern
Weight gain
Problems with balance
Reckless driving
Less writing, signature change
Urinary incontinence
Artistic abilities fade

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Medical Terms in FTD

aphasia: A loss of the ability to produce and/or understand language due to injury to brain areas specialized for these functions.

atrophy: Wasting away or shrinking. Neuronal atrophy is wasting away of neurons, a decrease in neuronal density.

cellular inclusion: Any small intracellular body found within a cell.

 dementia: A deterioration of intellectual faculties, such as memory, concentration and judgment, resulting from an organic disease or disorder of the brain. It is sometimes accompanied by emotional disturbance and personality changes.

 frontal lobe: The part of each hemisphere of the brain located behind the forehead that serves to regulate and mediate the higher intellectual functions. The frontal lobes have intricate connections to other areas of the brain. In the frontal lobes, we meld emotions, cognition, error detection, volition, a sense of self, and more to create our social brain.

frontal variant FTD (fvFTD): an older term for behavioral variant FTD (bvFTD)

frontotemporal dementia (FTD): The umbrella term for the clinical syndromes of behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). These syndromes share involvement of the frontal and temporal lobes of the brain. This term is sometimes used to refer specifically to bvFTD.

frontotemporal lobar degeneration (FTLD): the term that describes the specific pathological diseases that result in FTD syndromes. Subtyping is based on the specific proteins found within neuronal inclusions.

neuronal inclusion: Any small intracellular body found within a neuron (nerve or brain cell).

Pick bodies: A specific type of cellular inclusion made up of the protein tau and seen in some people with FTD.

Pick’s disease: another name for behavioral variant frontotemporal dementia (bvFTD), which has also been called frontotemporal dementia (FTD) and frontal variant frontotemporal dementia (fvFTD)

PPA (primary progressive aphasia): A neurodegenerative disease marked by the progressive decline of language functions. PPA has now been split into three subgroups: semantic dementia (SD), progressive nonfluent aphasia (PNFA) and logopenic progressive aphasia (LPA).

progressive non-fluent aphasia (PNFA): one of the language variants of frontotemporal dementia (FTD)

semantic dementia (SD): one of the language variants of frontotemporal dementia (FTD)

semantic paraphasia: The substitution of a word that is closely related to the target word, as in “cat” for “dog.”

tau: A protein in the body that aids in the cellular structure (cytoskeleton) and cellular transportation.

temporal lobe: The lobe of the cerebral hemisphere located down on the side of the brain near the ears. The temporal lobe contains the auditory cortex which is responsible for hearing, language comprehension and memory.

temporal variant frontotemporal dementia (tvFTD): an older term for the language variants of FTD (SD and PNFA)