Probable Early-onset Alzheimer s Disease Diagnosed by Comprehensive Evaluation and Neuroimage Studies

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1 Case Report Taiwanese Journal of Psychiatry (Taipei) Vol. 25 No Probable Early-onset Alzheimer s Disease Diagnosed by Comprehensive Evaluation and Neuroimage Studies Sin-Yi Chen, M.D. 1, Yuan-Han Yang, M.D. 2, Wen-Chen Ouyang, M.D., Ph.D. 3,4,5 Objective: We present a case of a female patient who was diagnosed with early-onset dementia after we did a comprehensive evaluation. Case Report: This 50-year-old female patient who showed insidious memory impairment, disturbances in executive functioning, and significant impairment in occupational functioning. Under the assumption of early-onset Alzheimer s dementia (AD) ( <65 years of age), we completed a detailed clinical history and physical examination as well as neuropsychological tests. The patient also received neuropsychiatric evaluation, brain magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT). Conclusion: Early-onset AD was strongly suggested basing on the findings of the clinical history, neuropsychiatric evaluation, physical examination, as well as brain MRI and brain SPECT studies. Therefore, early-onset dementia, especially in patients younger than 50 years, is rare. Accurate diagnosis of dementia subtypes is challenging. In addition to comprehensive examination, neuroimaging study can provide additional information for differential diagnosis. Key words: Early-onset dementia, Alzheimer s disease, single photon emission computed tomography, neuroimaging (Taiwanese Journal of Psychiatry [Taipei] 2011; 25: 45-9) Introduction Early-onset dementia, especially when patient s age of onset is under 50 years old, is rare; prevalence ranges from 0.067% to 0.081% in the 45 to 65 age group [1, 2]. Since early-onset dementia is associated with high psychiatric morbidity and a heavy caregiver burden, it is increasingly recognized as an important clinical and social problem. Alzheimer s disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD) are three most common subtypes of early-onset dementia [3, 4]. Clinical diagnosis of those conditions at an early stage can be difficult. Although 1 Department of General Psychiatry, Jianan Mental Hospital, Tainan, Taiwan 2 Department of Neurology, Kaohsiung Medical University, Kaohsiung, Taiwan. 3 General Clinical Research Center and Department of Geriatric Psychiatry, Jianan Mental Hospital, Tainan,Taiwan 4 School of Nursing, Griffith University, Brisbane, Australia 5 College of Medical and Life Science, Chung Hwa University of Medical Technology, Tainan, Taiwan Received: June 24, 2010; revised: August 5, 2010; accepted: November 1, 2010 Address correspondence to: Dr. Wen-Chen Ouyang, Jianan Mental Hospital, No. 80, Lane 870, Jhung-Shan Road, Rende District, Tainan 71742, Taiwan.

2 46 Early-onset Alzheimer s Disease and Imaging Study definitive diagnosis of dementia requires histopathological examination of brain tissue, such exams are rarely performed, either in Taiwan or internationally. Diagnosis must therefore rely on clinical history and assessment, laboratory testings, and established diagnostic criteria, and supported findings of neuroimaging [5]. We present a case in which the patient received detailed clinical history analysis, comprehensive physical examination, and neuropsychiatric evaluation for diagnosis of dementia. We also arranged for the patient to receive neuroimaging, including brain SPECT and MRI, for differential diagnosis of early-onset dementia. Case Report This 50-year-old female patient who had the background of elementary school education. Being accompanied by relatives during visits, she was reported to suffer from progressive memory impairment for at least one year. She had become globally forgetful, to repeat the same actions often, and not being able to remember things which had been told to her only a few minutes previously. She also showed disturbances in executive functions such as planning, organizing, and abstract thinking. One year before clinical admission, she could not longer work efficiently and lost her job which she had maintained for 20 years. Before further clinical examination, she revealed no other signs of central nervous system or systemic physical disease. According to the reports from the family, she did not have any obvious personality change, and symptoms or signs of depression or anxiety in her adulthood. Her relatives also denied any significant past history of her psychiatric disease or substance abuse. The patient was then admitted to our ward for seven days for further evaluation. She received a comprehensive dementia evaluation, including physical, neurological, and mental status examinations. Basically, laboratory examinations ( including tests for CBC, hematological data, liver function, renal function, biochemistry, serum levels of free T4, thyroid-stimulating hormone, and calcium, HIV titer, syphilis serology, B12, and folic acid), as well as neuropsychological tests including the Cognitive Abilities Screening Instrument [CASI], Mini-Mental State Examination [MMSE], AD-8 [6, unpublished conference abstract by CK Liu, MC Chou, CL Lei, et al, 2009], and Clinical Dementia Rating [CDR]. She also received brain MRI and SPECT examinations. The patient had normal results in physical examination, laboratory assessments and neurological examination. MMSE showed the findings of poor short-term memory, abstract thinking, and calculation ability. The patient had a CASI score of 23 (cut-off value being 64), an MMSE score of 6 (cut-off value being 17or 18), a CDR score of 1.0, and an AD-8 score of 1/8 being correct [6]. Brain MRI showed the finding of mild cerebral cortical atrophy. SPECT pictures of the brain revealed decreased radioactivity in mesial aspect, inferior portion of both temporal lobes (left side being much more severe than the right side), of the left parieto-temporal region; and mildly decreased radioactivity in adjacent bilateral frontotemporal regions. Under the assumption of earlyonset AD, we gave her donepezil, an acetylcholine esterase inhibitor (AChEI), to improve her cognitive function after discharge. The patient had thus far not suffered any other psychiatric symptoms such as hallucinations or delusions of theft or misidentification after her receiving treatment with donepezil, which was titrated up to 10 mg per day in the outpatient clinic. At a half-year follow-up at an outpatient clinic,

3 Chen SY, Yang YH, Ouyang WC 47 the patient's MMSE score had improved to 8 with a stable clinical course. Her appetite had remained good without any weight loss. But her daily activities need the caregiver s help due to her forgetfulness and disorientation. Discussion Early-onset dementia has increasingly been recognized as an important clinical and social problem, and is a demoralizing and frustrating condition for both patients and caregivers. AD, VaD and FTD are three most common causes of early-onset dementia, and early diagnosis of those conditions can be problematic [3, 4]. In the absence of a robust biological marker, diagnosis relies mainly on clinical history and characteristics, and requires thorough physical, neurological, and psychiatric examinations for symptoms and signs. Brain imaging may consist of either SPECT or MRI [8,11]. The recent availability of new treatments for dementia as well as the importance of subtype-specific management, have renewed interest in the use of brain imaging for accurate recognition of AD, VaD and FTD. We therefore reviewed articles discussing how to make differential diagnosis of the subtypes of dementia. Although the dementia subtypes have more overlapping signs and symptoms [9], some key aspects still exist from history, physical examination, and diagnostic tests for differential diagnosis of the subtypes of dementia [9]. In the current case, we reviewed articles concerning differences between early- and late-onset dementia and differential diagnosis of dementia subtypes. The presence of cerebrovascular events or hemiparalysis histories, and focal neurological signs or symptoms is reliable for differentiating VaD from AD. Our patient did not have any history of cardiovascular disease, had insidious onset of dementia without sudden or stepwise course, and had characteristic findings of clinical examination and imaging examinations. Therefore, our patient was unlikely to be a case of VaD [9-11]. FTD also seemed to be doubtful, because memory impairment is rarely seen as the initial symptom. FTD typically involves the presence of disinhibition, personality change, disorganized behaviors, and hallucinations in the early stages [9]. Earlystage AD often has clinical features of short-term memory impairment and apathy without delusions and hallucinations. This picture was seen in our patient. But early-onset AD is rare, and an onset age under 50 is extremely rare. Therefore, more clinical evidence is needed to support an AD diagnosis. The fact that the patient s cognition and MMSE score did not worsen appreciably after a six-month ChEI treatment may be a clinical evidence supporting a diagnosis of AD. When we reviewed relevant papers concerning neuroimaging of dementia, some references mentioned that SPECT is a widely used technique for studying the functional properties of the brain [11, 12]. In addition, the use of brain imaging as a diagnostic tool for AD has been discussed extensively [13, 14]. In SPECT examination, our patient was found to have decreased perfusion in both temporal and parietal areas, but not in the frontal and occipital areas. Such differences may imply that the patient suffered from AD. Based on our review of relevant literature, we summarize the key aspects of differential diagnosis and identification of dementia subtypes in Table 1 [8-10]. Although hippocampal atrophy is considered an important sign of AD, its detection cannot be easily done in routine examinations. So far, we have not had any accepted value standard for the volume of the hippocampus, especially in Taiwan. Moreover, the degree of atrophy of hippocampus in the early

4 48 Early-onset Alzheimer s Disease and Imaging Study Table 1. The differential diagnosis and distinguishing of the dementia subtypes The Subtypes of Dementia Alzheimer s dementia (AD) Vascular Dementia (VaD) Frontotemporal Dementia (FTD) Core symptoms [9, 10] Pathology [9, 10] Image findings [8] Anterograde amnesia Beta-amyloid plaques CT: generalized cerebral atrophy, (inability to learn and Neurofibrilary tangles ventricular enlarge- retain new information) ment and mild to moderate Impaired reasoning, visuo-spatial white matter changes or ability, ori- leukoaraiosis entation, language, and MRI: Atrophy of the hippocampus handling of complex and entorhinal cor- tasks tex SPECT: temporoparietal hypoperfusion Anterograde amnesia (inability to learn and retain new information) Onset or worsening occurred within 3 months of a stroke or evidence on neuroimaging of bilateral infarctions in subcortical or cortical gray matter (i.e., silent stroke) Personality change or decline in regulation in personal or interpersonal conduct Impaired reasoning or handling of complex tasks, out of proportion to impairments of recent memory spatial ability Evidence of CT and MRI: Evidence of cerebralvascular disease cerebralvascular disease and infarction and infarction SPECT and PET: classically gives a variable multifocal pattern in VaD One of the following FTD is characterized by a usually present: strong gradient of atrophy Pick bodies from anterior to posterior Tau-positive corticobasal degeneration along the temporal lobe, as opposed to AD when atro- Frontotemporal degeneration phy occurs throughout. with no distinc- Atrophy may be more fophy tive histopathology cally located around the frontal lobe in FTD associated with motor neurone disease; but more widespread, affecting also the temporal lobes in other cases of FTD

5 Chen SY, Yang YH, Ouyang WC 49 stage of AD is relatively mild compared to that in the advanced AD. Our patient might not have the marked degree of atrophy of hippocampus that can be detected in an MRI examination. In conclusion, although early-onset dementia is uncommon, especially before the age of 50 years, we diagnosed as having dementia with DSM-IV-TR criteria based on basis her detailed clinical history, as well as the findings of physical examination and comprehensive neuropsychiatric evaluation. We also did the neuroimaging study to further supportive diagnosis. Diagnosis of earlyonset dementia is an important issue not only for patients, but also for their family and caregivers due to the imposed heavy burden of this condition. The subtype diagnostic and comprehensive evaluation process for early-onset dementia includes the findings of clinical history, physical, neurological, and mental status examination as well as laboratory testing and psychological testing. Finally, neuroimaging study, may be worth obtaining to make accurate differential diagnosis of patients with early-onset dementia. Acknoledgement This study was partially supported by grants from the Department of Heath, Taiwan (DDH98- PA-1001-I; DDH99-FDA G). References 1. Harvey RJ, Rossor MN, Skelton-Robinson M, et al.: Young-onset Dementia: Epidemiology, Clinical Symptoms, Family Burden, Support and Outcome. London: Dementia Research Group, E L Sampson, J D Warren, M N Rossor: Young onset dementia. Postgrad Med J 2004; 80: Ratnavalli E, Brayne C, Dawson K, et al.: The prevalence of frontotemporal dementia. Neurology 2002; 58: Harvey RJ, Skelton-Robinson M, Rossor MN: The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003; 74: American Academy of Neurology. Practice parameter for diagnosis and evaluation of dementia (summary statement): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1994; 44: James E Galvin JERoe CM, Coats MA, Morris JC: Patient s Rating of Cognitive Ability : Using the AD8, a Brief Informant Interview, as a Self-rating Tool to Detect Dementia. Arch Neurol 2007; 64: Liu CK, Chou MC, Lai CL, et al.: Application of AD-8 to screen very mild dementia in Taiwan. International Conference of Alzheimer s Disease 2009: Varma AR, Adams W, Lloyd JJ, et al.: Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer s disease, fronto-temporal dementia and vascular dementia. Acta Neurologica Scand 2002; 105: Amanda F: Key points in differential diagnosis of dementia. Geriatrics 2009; 64: Coin A, Najjar M, Catanzaro S, et al.: A retrospective pilot study on the development of cognitive, behavioral and functional disorders in a sample of patients with early dementia of Alzheimer type. Arch Gerontol Geriatr 2009; 49 (Suppl 1): O Brien JT: Role of imaging techniques in the diagnosis of dementia. Brit J Radiol, 2007; 80: S71-S77N. 12. English R J, Brown SE: SPECT: Single-photon Emission Computed Tomography, A Primer. New York: Society of Nuclear Medicine, Jagust W, Thisted R, Devous M D, et al.: SPECT perfusion imaging in the diagnosis of Alzheimer s disease. Neurology 2001: 56: McNeill R, Sare G M, Manoharan M, et al.: Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer s disease. J Neurol Neurosurg Psychiatry 2007; 78:

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