Alzheimer Disease Imaging CT Scan The initial criteria for CT scan diagnosis of Alzheimer disease includes diffuse cerebral atrophy with enlargement of the cortical sulci and increased size of the ventricles. A multitude of studies indicated that cerebral atrophy is significantly greater in patients with Alzheimer disease than in patients who are aging without Alzheimer disease. This concept was soon challenged, however, because cerebral atrophy can be present in elderly and healthy persons, and some patients with dementia may have no cerebral atrophy, at least in the early stages. The extent of cerebral atrophy was determined by using linear measurements; in particular, bifrontal and bicaudate diameters and the diameters of the third and lateral ventricles. Various measurements were adjusted according to the diameter of the skull to account for normal variation. To complement this modification, volumetric studies of the ventricles were done. Despite these efforts, it is still difficult to distinguish between findings in a healthy elderly patient and those in a patient with dementia. In addition, a review of serial CT scans obtained over several months was not clinically useful in the primary diagnosis of the disease. Rate of change of brain atrophy Changes in the rate of atrophy progression can be useful in diagnosing Alzheimer disease.Longitudinal changes in brain size are associated with longitudinal progression of cognitive loss,and enlargement of the third and lateral ventricles is greater in patients with Alzheimer disease than in control subjects. Changes in brain structure Diffuse cerebral atrophy with widened sulci and dilatation of the lateral ventricles can be observed. Disproportionate atrophy of the medial temporal lobe, particularly of the volume of the hippocampal formations (< 50%), can be seen. Dilatation of the perihippocampal fissure is a useful radiologic marker for the initial diagnosis of Alzheimer disease, with a predictive accuracy of 91%.[SUP][15] [/SUP]The hippocampal fissure is surrounded laterally by the hippocampus, superiorly by the dentate gyrus, and inferiorly by the subiculum. These structures are all involved in the early development of Alzheimer disease and explain the enlargement in the early stages. At the medial aspect, the fissure communicates with the ambient cistern, and its enlargement on CT scans is often seen as hippocampal lucency or hypoattenuation in the temporal area medial to the temporal horn. The temporal horns of the lateral ventricles may be enlarged. Prominence of the choroid and hippocampal fissures and enlargement of the sylvian fissure may be noted. White matter attenuation is not a feature of Alzheimer disease. Degree of confidence CT scan indices of hippocampal atrophy are highly associated with Alzheimer disease, but the specificity is not well established. Use of a nonquantitative rating scale showed a sensitivity of 81% and a specificity of 67% in differentiating 21 patients with Alzheimer disease with moderate dementia from 21 age-matched control subjects.[SUP][16] [/SUP]Hippocampal volumes in a sample of similar size permitted correct classification of 85% of control subjects. ref - http://emedicine.medscape.com/article/336281-overview#aw2aab6b3 ********************************************************************************* Self Assessment Questions on Alzheimer's Disease Question 1 of 3 A 72-year-old man comes to your clinic for the first time, accompanied by his wife. His wife states that she is concerned because he has been growing increasingly forgetful over the past year. Within the past month, he has forgotten to turn off the stove and has got lost while walking to the post office one block away from their home. His past medical history is significant for well-controlled diabetes and chronic lower back pain. He has no history of falls or traumatic injury to the head. Examination of the patient is significant for a score of 18 on a Mini-Mental Status Examination (MMSE). During the administration of the MMSE, the patient blurts out that his wife brought him to the doctor because she is having an extramarital relationship. Which of the following accurately describes this patient's condition? A. There is no genetic basis for development of this disease. B. It is usually abrupt in onset. C. There is no correlation between age and prevalence of this disease. D. Environmental exposure is a proven risk factor for development of this disease. E. It is one of the most common terminal illnesses in developed nations. The answer is E. Question 2 of 3 A 72-year-old man comes to your clinic for the first time, accompanied by his wife. His wife states that she is concerned because he has been growing increasingly forgetful over the past year. Within the past month, he has forgotten to turn off the stove and has got lost while walking to the post office one block away from their home. His past medical history is significant for well-controlled diabetes and chronic lower back pain. He has no history of falls or traumatic injury to the head. Examination of the patient is significant for a score of 18 on a Mini-Mental Status Examination (MMSE). During the administration of the MMSE, the patient blurts out that his wife brought him to the doctor because she is having an extramarital relationship. Use of which of the following medications would be the most likely to lead to worsening of symptoms in this patient? A. risperidone B. amitriptyline C. olanzapine D. quetiapine E. trazodone The answer is B. Question 3 of 3 A 72-year-old man comes to your clinic for the first time, accompanied by his wife. His wife states that she is concerned because he has been growing increasingly forgetful over the past year. Within the past month, he has forgotten to turn off the stove and has got lost while walking to the post office one block away from their home. His past medical history is significant for well-controlled diabetes and chronic lower back pain. He has no history of falls or traumatic injury to the head. Examination of the patient is significant for a score of 18 on a Mini-Mental Status Examination (MMSE). During the administration of the MMSE, the patient blurts out that his wife brought him to the doctor because she is having an extramarital relationship. Despite appropriate treatment, the patient experiences a gradual decline in mental function. He develops erratic sleep habits, frequently awakening at night and wandering throughout his home. His wife states that she once found him sitting on the ground in their yard, unable to recall how he arrived there. During your latest examination of the patient, you note that he has lost the ability to sign his name, holding the pen as if he is unsure of what to do with it. Exasperated, his wife states that he is now dependent on her for performance of his activities of daily living. Which of the following is indicated in the treatment of the patient's condition at its current severity? A. tacrine (Cognex) B. gingko biloba C. rivastigmine (Exelon) D. memantine (Namenda) E. galantamine (Reminyl) The answer is D. EXPLANATION: This patient's symptoms are most consistent with Alzheimer disease. Alzheimer disease is a prominent condition in developed nations, ranking as the third most common terminal illness behind heart disease and cancer. It is the most common form of dementia, with over 4 million Americans having the condition in the United States alone. There is a direct correlation between advanced age and increasing prevalence of Alzheimer disease. While there is an early-onset form of familial Alzheimer disease that may appear as early as the third decade of life, this accounts for only a small percentage of total Alzheimer cases. There does appear to be a genetic component to the development of Alzheimer disease, as it has been demonstrated that first-degree relatives of Alzheimer patients possess an increased risk for development of the condition. Genes on chromosomes 1, 14, and 21 have been implicated in this association. While age and family history are important risk factors, there is no evidence proving that environmental factors lead to an increased chance for development of the disease. Progression of Alzheimer dementia is typically insidious, spanning as many as several years. Anticholinergic agents and any other medication with anticholinergic effects are contraindicated in the setting of Alzheimer dementia. Their use may lead to worsening of cognition and may contribute to decreased efficacy of medications used in the treatment of Alzheimer dementia. Tricyclic antidepressants such as amitriptyline should be avoided for this reason. Risperidone, olanzapine, and quetiapine are atypical antipsychotic medications which are useful in the treatment of emotional withdrawal and delusions which may arise in Alzheimer patients. Trazodone, carbamazepine, and divalproex are mood-stabilizing medications which are useful in patients who display marked agitation. While trazodone does display some anticholinergic side effects, they are far less pronounced than those seen with amitriptyline. Memantine, the only drug listed as an option that is approved for the treatment of moderate-to-severe Alzheimer disease, is an NMDA receptor antagonist and the first Alzheimer drug of this type approved in the United States. It blocks the activity of glutamate, a neurotransmitter involved in information processing, storage, and retrieval. NMDA receptors facilitate calcium influx into neurons. Too much calcium, though, can result in cell death. All of the other drugs are acetylcholinesterase inhibitors that increase the concentration of acetylcholine in the brain. ********************************************************************** The Rational Clinical Examination > Dementia > Original Article: Does This Patient Have Dementia? > Section Authors: Tracey Holsinger, Janie Deveau, Malaz Boustani, John W. Williams, Jr [TABLE] [TR] [TD="bgcolor: #FFFFFF"]Clinical Scenario Ms A, an 81-year-old retired nursing instructor who is recently widowed and lives alone, arrives in your office. She is accompanied by her daughter who decided to miss work and attend the appointment because she wanted you to know that her mother has become increasingly forgetful during the past 6 months. The patient is misplacing her glasses and keys more often, and she complains of difficulty sleeping and poor concentration. You must address whether the memory complaints are indicative of a dementia or if she has anxiety, depression, or is merely noting poorer recall associated with normal aging. [TABLE] [TR] [TD="bgcolor: #FFFFFF"]Scenario Resolution A patient presenting with subjective complaints of memory impairment should be evaluated for dementia, delirium, and depression. You do a Mini-Mental State Examination with Ms A who scores 28/30 points. She misses 1 point for concentration and 1 for recall of words after a delay. She denies feeling depressed and enjoys shopping and spending time with her friends and family. Her PHQ-9 (the patient health questionnaire, a depression measure) score is 6 indicating minimal depressive symptoms. She consents to your discussing her situation with her daughter who reports that for the last 6 months her mother has been forgetting recent conversations, failed to remember a lunch appointment, and forgot to pay some of her bills. There is no evidence of an altered level of consciousness. You decide that given her educational level, she should undergo another screening. You administer the Hopkins Verbal Learning Test and based on her score of 17, decide there is a reasonably high likelihood that she may have dementia. You refer her for further evaluations. These evaluations should include a medical history, physical examination, and laboratory testing, and may include neuroimaging and neuropsychological testing. [/TD] [/TR] [/TABLE] Conclusion Many instruments exist for evaluating a patient with suspected cognitive impairment. For many reasons, including time-constrained general medical appointments, the subtlety of early impairment, and the poor sensitivity of many brief screening instruments, no single instrument is ideal for all settings (Box 63-2). To determine the presence and severity of cognitive impairment that is at least moderate in degree, the MMSE is the most studied instrument and a reasonable choice. Clinicians who have not memorized the MMSE must either administer it from an approved copy[SUP]72,73[/SUP] or purchase copies. If a brief instrument is needed and sensitivity is not of paramount importance, a quick screen such as the Memory Impairment Screen or a scored clock test can be used. When more time is available to evaluate cognitive status, the Cambridge Cognitive Examination, Modified Mini-Mental State Examination, or Community Screening Interview for Dementia may yield greater accuracy. To look for cognitive decline in a high-functioning, educated population, an instrument with less of a ceiling effect is required (such as word list acquisition test or Hopkins Verbal Learning Test), but none are short and readily administered in a primary care setting. [TABLE] [TR] [TD][/TD] [TD="class: font12"]Most Practical Screening Instruments for Generalist Physicians by Clinical Issue and Appropriate Test [/TD] [TD="class: font12"][/TD] [/TR] [/TABLE] [TABLE] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Want to Find Cognitive Impairment of at Least Moderate Severity[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Mini-Mental State Examination[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Suspicion of Mild Impairment or Highly Educated Patient[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Hopkins Verbal Learning Test or the Word List Acquisition Test[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Very Little Time Available[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Memory Impairment Screen or the Clock Drawing Test[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Plenty of Time Available[/TD] [/TR] [TR="class: font12"] [TD="class: font10, bgcolor: #ffffff, align: left"]Cambridge Cognitive Examination, Modified Mini-Mental State Examination, Community Screening Interview for Dementia, or the Montreal Cognitive Assessment [/TD] [/TR] [/TABLE] [/TD] [/TR] [/TABLE] *************************************************************************************
