Mr. J is a 59-year-old married man who is the vice president of a large accounting firm. He comes to see his internist accompanied by his wife. Mrs. J tells Dr. G that she is extremely concerned about her husband. He has been forgetful at times, such as eating dinner and then coming to her an hour later asking, “What’s for dinner?” She reports that her husband, a usually quiet man, has been talking to strangers, often carrying on long conversations about small details, such as whether the price of postage stamps is too high. Mr. J has been socially inappropriate at times, often kissing and grabbing his wife in restaurants or in front of friends. Mrs. J reports that he often gets up at night and eats large amounts of food, something he never did in the past.
Mr. J seems to be performing well on his job and has recently acquired several large clients for the firm. At a recent office party, several coworkers joked with Mrs. J about her husband’s new habit of coming to work without socks and walking barefoot in his office. Mr. J has a history of hypertension that has been well-controlled on benazepril 10 mg with hydrochlorothiazide 25 mg once daily. He drinks alcohol occasionally. Dr. G observes that Mr. J appears unusually talkative, commenting at length about the doctor’s blue striped necktie. He walks around the exam room, tells sexually related jokes, and uses several obscenities. This is a marked change from the reserved, business-like man Dr. G has cared for over the past 10 years.
Dr. G starts thinking of a differential diagnosis, including a possible stroke or psychiatric illness. He undertakes a physical examination, electrocardiogram (ECG), and fingerstick glucose, all of which are normal. On the Mini-Mental State Examination, Mr. J scores 28 out of 30. Of concern was that he is unable to name the items “pencil” and “watch,” instead giving a definition of “a writing instrument used for centuries to provide information for the masses.” Dr. G orders laboratory tests, including complete blood count, chemistry panel, thyroid profile, and vitamin B12, folate, and urine toxicology levels. He decides to ask Mr. J to sign a consent for HIV testing, which prompts another series of sexually explicit jokes.
Dr. G refers Mr. J to a neurologist who reviews his laboratory tests, finding no abnormalities. Mr. J undergoes a lumbar puncture, with normal results, including testing for Creutzfeldt-Jakob proteins. The neurologist sends Mr. J for magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of the brain, and asks Mrs. J and her two sons to submit blood samples for genetic testing. The neurologist tells Mr. and Mrs. J that he has a serious disorder and recommends a brain biopsy. Mr. J insists that he is fine and refuses further testing. Mrs. J calls Dr. G in a highly anxious state. She asks for help clarifying her husband’s diagnosis and how they should proceed. Dr. G arranges to meet with the family to discuss the findings and recommendations.
Pick’s disease is a type of dementia marked by prominent changes in behavior, mood, social skills, and personality, followed by progressive decline in memory and loss of executive functioning.1 Cortical atrophy selective to the frontal and temporal lobes makes this disorder distinct from dementia of the Alzheimer’s type, as does the early age of onset, which is typically before the age of 60 years. The Czechoslovakian neurologist Arnold Pick was the first to describe this syndrome in 1892. His colleague, Dr. Alois Alzheimer, later described the unique pathologic features of this disease, including enlarged neurons containing homogeneous, smooth intracytoplasmic inclusion bodies that are identified with silver staining.2 These were later named Pick bodies, noting their differentiation from the neurofibrillary tangles that characterize Alzheimer’s dementia.3
Pick’s disease is now known to be one of several types of frontal lobe dementias (FLDs).3 Frontal lobe dementias preferentially affect the frontal and temporal lobes, with varying degrees of atrophy, motor involvement, and genetic inheritance. These syndromes include frontotemporal degeneration (FTD), frontotemporal degeneration with parkinsonism (FTDP), and corticobasal ganglionic degeneration (CBGD).4 These distinctions are still evolving as correlations between clinical presentation and neuropathology are further identified. Only 20% of cases of all frontotemporal dementias are associated with Pick bodies, although selective atrophy of the frontal and, to a lesser degree, the temporal lobes, is a common feature of all of these syndromes.5 The clinical presentation of Pick’s disease in its early stage includes the insidious onset of personality, behavior, and mood changes.4 This may include depression, elation and euphoria, disinhibition, and irritability.
As Pick’s disease may involve significant atrophy of the frontal and bilateral anterior temporal lobes, the clinical features of the disorder are often distinctive and striking. Socially inappropriate behavior may occur. In some patients, elements of Klüver-Bucy syndrome, including hypersexuality, hyperphagia, and hyperactivity, develop.2 Visual agnosia and disturbance of executive functioning are often more prominent than memory loss in the early stages of the disease.1 However, as the dementia progresses, decline in speech, loss of self-care skills, and overt impairment in memory are inevitable (Table).1-4 In the United States, Pick’s disease accounts for up to 5% of all dementias.3 It is an early-onset dementia, with the majority of cases presenting between the ages 50 and 60 years. Cases have been identified in patients as young as 21 years. Late-onset cases of patients as old as 80 years have been found at autopsy.1,2 The majority of cases of Pick’s disease are sporadic in nature, with no clearly identifiable family history of FLD or other dementia.6
In approximately 5% of cases, a pattern of family inheritance appears to indicate an autosomal dominant form of inheritance, but no genetic mutation has been identified. In one family, an abnormality located on chromosome 3 was associated with transmission of the disease, but this has not been replicated in larger populations.5 The subtype FTDP has been associated with a mutation of the tau gene, located on chromosome 17q21-22. This mutation is not specific to FTDP and has been associated with other movement disorders as well as psychosis, including familial schizophreniform disorder.1,6 Referral to a genetic counselor for further assessment may be useful if there is a significant family history of dementia; however, there is no genetic testing that is routinely suggested for Pick’s disease. There is no specific treatment for Pick’s disease, and no controlled trials of medications have been conducted. Some clinicians have empirically utilized cholinesterase inhibitors in an attempt to slow the progression of the disease.2
Symptom management with selective serotonin reuptake inhibitors for the treatment of mood disorders has been utilized.1 Given the prominent symptoms of disinhibition, hyperactivity, hypersexuality, and personality change that often occur early in the disease, psychiatric consultation for management is often helpful. As Pick’s disease is a disorder with onset at a young age, while the patient is often still working, advance planning should begin as soon as possible. Referral to lawyers and financial planners early in the course may be vital for obtaining financial aid, arranging advance directives and power of attorney, and protecting the financial assets of the family in order to provide for both living expenses and long-term care.1,2
Unlike Alzheimer’s or vascular dementia, patients with Pick’s disease often become impaired prior to retirement age, when issues of disability income, insurance coverage, and management of family finances may be more complex. This only adds to the stress and burden of the family and caregivers. Information for family members and caregivers may be obtained from the Association for Fronto-temporal Dementias (AFTD), www.FTD-Picks.org, and the National Organization for Rare Disorders (NORD), www.rarediseases.org.
OUTCOME OF THE CASE PATIENT
Mrs. J returns to meet with Dr. G, accompanied by her two sons, a 20-year-old college student and a 25-year-old attorney. All three family members are very upset by the information they received from the neurologist, and complain that he stopped returning their calls after Mr. J refused to undergo a brain biopsy. Dr. G senses a mixture of anger and desperation as they speak. Dr. G finds that the neurologist performed an extensive and thorough battery of tests, including MRI and PET scans that revealed marked frontal and anterior temporal lobe atrophy as well as reduced glucose metabolism in these regions. In the absence of any treatable condition, a clinical diagnosis of Pick’s disease appears likely. The neurologist is conducting a study of the genetics of FTDs, and recommended both a brain biopsy and genetic testing of the family. Dr. G finds that there is no family history of dementia; in fact, Mr. J’s parents and grandparents lived independently well into their 80s. He suggests that the family focus more on planning for Mr. J’s future needs. Fortunately, Mr. J completed a living will and power-of-attorney documents while his older son was in law school. Mr. J is still going to work, but the partners at his firm are meeting to discuss an early retirement package for him. Mr. J refused to come to Dr. G’s office, stating that he has seen enough doctors and is not sick. Dr. G refers the family to a dementia support group, and arranges for them to meet with a care manager to discuss options for Mr. J, such as volunteer work or a day program. By the end of their meeting, Mrs. J is in tears, and her sons start arguing about the need for another opinion. Dr. G suggests that the family review educational materials about Pick’s disease and arranges for an appointment with a social worker. He calls Mr. J to arrange a follow-up visit, and hopes that he can help his patient over what may be a lengthy and progressive decline.