A 55-year-old, previously healthy man is brought to the office by his wife after being forced into early retirement due to poor work performance. The patient was a financial planner but began missing important deadlines and mismanaging his client's accounts 6 months ago. He became more irritable during this time and started to curse at and insult his coworkers when they expressed concern about his performance. The patient has also become verbally abusive toward his wife but appears indifferent to the hurt he causes. She has had to take over the finances and grocery shopping. She adds, "My husband has developed quite the sweet tooth. He eats almost two boxes of cookies a day now." Physical examination is unremarkable. This patient is most likely to have which of the following neuropathologic findings?

Question

A 55-year-old, previously healthy man is brought to the office by his wife after being forced into early retirement due to poor work performance.  The patient was a financial planner but began missing important deadlines and mismanaging his client's accounts 6 months ago.  He became more irritable during this time and started to curse at and insult his coworkers when they expressed concern about his performance.  The patient has also become verbally abusive toward his wife but appears indifferent to the hurt he causes.  She has had to take over the finances and grocery shopping.  She adds, "My husband has developed quite the sweet tooth.  He eats almost two boxes of cookies a day now."  Physical examination is unremarkable.  This patient is most likely to have which of the following neuropathologic findings?

Quizplus · Accepted Answer

11ec160b_3626_da7a_9249_f3f582132e64_MD0001_00 This patient with impaired executive function (eg, poor work performance) most likely has frontotemporal dementia (FTD), a type of early-onset dementia characterized by prominent behavioral changes. These can include: Disinhibition: socially inappropriate behavior (eg, cursing at coworkers) Apathy/loss of empathy: loss of interest in activities and/or impaired social relationships (eg, indifference toward being verbally abusive) Hyperorality: changes in diet, often with a preference for sweets; more severe manifestations include binge eating (eg, eating 2 boxes of cookies per day) or consuming inedible objects Compulsive behaviors: may include simple (eg, repetitive speech or motions) or complex (eg, hoarding, following a new religion) behaviors FTD is characterized by degeneration of the prefrontal cortex, progressing to include the anterior temporal lobes. Neuropathologic features often overlap with other neurodegenerative conditions and may include: Aggregations of phosphorylated tau protein: Tau is a protein associated with neuronal microtubules, and it normally takes part in microtubule stabilization. In patients with FTD, tau becomes hyperphosphorylated and disassociates from the microtubules, which may lead to instability and disrupted axonal transport. Phosphorylated tau aggregates to form inclusions that can appear as neurofibrillary tangles (similar to those seen in Alzheimer disease) or round inclusions (ie, Pick bodies). Abnormal TDP-43 protein inclusions: TDP-43 is a protein involved in DNA repair and transcription, and it becomes abnormally ubiquitinated in FTD. Pathologic TDP-43 is also found in patients with amyotrophic lateral sclerosis. (Choice B) Cytoplasm inclusions with alpha synuclein are characteristic of dementia with Lewy bodies, which is characterized by visual hallucinations, parkinsonism, cognitive fluctuations, and REM sleep behavior disorder. (Choice C) Cytosolic vacuolation of neurons and glia with prion inclusions are seen in patients with Creutzfeldt-Jakob disease, a prion disease. Although behavioral changes are common, dementia is rapidly progressive and associated with myoclonus and/or seizures. (Choices D and E) Presenilin is a component of the gamma-secretase complex, which is involved in cleavage of the amyloid precursor protein (APP). Abnormal cleavage of APP leads to increased beta amyloid deposition that is commonly seen in patients with Alzheimer dementia. Alzheimer dementia commonly presents with early and prominent memory impairment with language deficits and spatial disorientation. Although personality changes can occur, they typically present later in the disease process. Educational objective: Frontotemporal dementia presents with early personality change, executive dysfunction, compulsivity, and hyperorality. Neuropathologic findings include neurofibrillary tangles due to abnormal tau proteins (also seen in Alzheimer dementia) and pathologically ubiquitinated TDP-43 (also seen in amyotrophic lateral sclerosis). __________ References: Frontotemporal dementia. (http://www.ncbi.nlm.nih.gov/pubmed/26595641)

A 55-Year-Old, Previously Healthy Man Is Brought to the Office