A 74-year-old woman comes to the office due to progressive forgetfulness over the past 2 years. Her family states that the patient asks the same questions repeatedly over the course of a day and often forgets what she is doing in the middle of chores. The patient has also been more irritable but has had no movement or gait abnormalities, feelings of depression, hallucinations, or delusions. Medical conditions include hypertension and renal artery stenosis. Vital signs are within normal limits. Mini-Mental State Examination score is 21 out of 30 and she recalls 1 out of 3 objects after 5 minutes. There are no focal neurologic deficits. Which of the following is most likely involved in the pathogenesis of this patient's condition?

Question

A 74-year-old woman comes to the office due to progressive forgetfulness over the past 2 years.  Her family states that the patient asks the same questions repeatedly over the course of a day and often forgets what she is doing in the middle of chores.  The patient has also been more irritable but has had no movement or gait abnormalities, feelings of depression, hallucinations, or delusions.  Medical conditions include hypertension and renal artery stenosis.  Vital signs are within normal limits.  Mini-Mental State Examination score is 21 out of 30 and she recalls 1 out of 3 objects after 5 minutes.  There are no focal neurologic deficits.  Which of the following is most likely involved in the pathogenesis of this patient's condition?

Quizplus · Accepted Answer

11ec160b_3b00_eb9a_9249_07293b3bdebc_MD0001_00 This older patient with impairment of recent memory and cognitive deficits in the absence of other focal neurologic findings most likely has Alzheimer disease (AD). Neuropathologic features of AD include: Tau is a protein associated with neuronal microtubules. Under normal conditions, tau takes part in microtubule stabilization. In AD, tau is hyperphosphorylated and disassociates from the microtubules, which may lead to instability and disrupted axonal transport. Hyperphosphorylated tau also makes paired helical filaments, which create intracellular neurofibrillary tangles, resulting in neuronal damage. Increased accumulation of these tangles is associated with progression of AD. (Choice A) Dementia with Lewy bodies (ie, alpha-synuclein protein aggregation) is characterized by fluctuating cognitive impairment, dysautonomia, parkinsonism, and visual hallucinations. This patient's progressive impairment of recent memory and unremarkable neurologic examination are more consistent with AD. (Choice B) Multiple sclerosis (MS) is an autoimmune disease targeting oligodendrocytes, the myelin-producing cells of the CNS. The pathogenesis involves inappropriate activation of CD4⁺ T lymphocytes by myelin basic protein. MS typically presents in young women (age <50) with neurologic deficits (eg, blurry vision, diplopia, focal weakness/numbness, bowel/bladder dysfunction) disseminated in time and space. (Choice C) This older patient with hypertension and renal artery stenosis likely has significant atherosclerosis; however, there is no evidence of vasculitis. Vasculitis affecting the CNS often presents with headache and focal neurologic deficits, rather than progressive memory impairment, due to obstruction of the inflamed vessels and subsequent tissue ischemia. (Choice E) Perivascular macrophage infiltration is characteristic of HIV-associated dementia, which occurs almost exclusively in untreated HIV-infected patients with advanced disease (eg, CD4⁺ <200). In contrast to the cortical dysfunction (ie, amnestic symptoms) seen in AD, HIV-associated dementia is a subcortical dementia characterized by apathy, early attention impairment, and subcortical motor symptoms. Educational objective: Neuropathologic features of Alzheimer disease include neurodegeneration, amyloid plaques (ie, extracellular accumulations of beta amyloid), and neurofibrillary tangles. Neurofibrillary tangles are formed when tau, a protein associated with neuronal microtubules, becomes hyperphosphorylated and disassociates from the microtubules to form paired helical filaments.

A 74-Year-Old Woman Comes to the Office Due to Progressive