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Analysis of Cerebrospinal Fluid and [11C]PIB PET Biomarkers for Alzheimer’s Disease with Updated Protocols

BACKGROUND Recently, a Korean research group suggested a consensus protocol, based on the Alzheimers Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. OBJECTIVE Here, we analyzed fluid and imaging biomarkers of Alzheimers disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. METHODS Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. RESULTS The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. The cutoff values of CSF t-Tau/Aβ42 and p-Tau/Aβ42 ratio- were 0.210 (sensitivity 100%, specificity 86.21%) and 0.1350 (sensitivity 88.46%, specificity of 92.86%). The concordance rate with PIB-PET was higher using the CSF t-Tau/Aβ42 ratio (κ= 0.849, CI 0.71-0.99) than CSF Aβ42 alone (κ= 0.703, CI 0.51-0.89). CONCLUSIONS Here, we improved controversial factors associated with the previous CSF study protocol and suggested a new cutoff value for the diagnosis of AD. Our results showed good diagnostic performance for differentiation of AD. Thus, we expect our findings could be a cornerstone in the establishment and clinical application of biomarkers for AD diagnosis.

Early Onset Alzheimer's Disease Presenting as Logopenic Primary Progressive Aphasia

Primary progressive aphasia (PPA) is a clinical syndrome, encompassing a group of patients who show slowly progressing dementia relatively restricted to the language area of the brain.1 The logopenic variant of PPA is the most recently identified subtype, characterized by slow word retrieval, impaired sentence repetition, and frequent word-finding pauses. On the other hand, motor speech, grammar, and single-word comprehension are often spared.2 Although logopenic PPA is diagnosed clinically, most cases share an underlying Alzheimers disease (AD) pathology.3 In this article, we report on a case of logopenic primary progressive aphasia with AD pathology, which developed into dementia caused by AD in the course of time.

Hydrocephalus in a Patient with Alzheimer's Disease

Background Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimers disease (AD). Case Report A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex. Conclusions The patient of NPH was unresponsive to shunt therapy due to the development of AD.

Decreased Metabolism in the Posterior Medial Network with Concomitantly Increased Metabolism in the Anterior Temporal Network During Transient Global Amnesia

Perturbation of corticohippocampal circuits is a key step in the pathogenesis of transient global amnesia. We evaluated the spatial distribution of altered cerebral metabolism to determine the location of the corticohippocampal circuits perturbed during the acute stage of transient global amnesia. A consecutive series of 12 patients with transient global amnesia who underwent 18F-fluorodeoxyglucose positron emission tomography within 3 days after symptom onset was identified. We used statistical parametric mapping with two contrasts to identify regions of decreased and increased brain metabolism in transient global amnesia patients compared with 25 age-matched controls. Transient global amnesia patients showed hypometabolic clusters in the left temporal and bilateral parieto-occipital regions that belong to the posterior medial network as well as, hypermetabolic clusters in the bilateral inferior frontal regions that belong to the anterior temporal network. The posterior medial and anterior temporal networks are the two main corticohippocampal circuits involved in memory-guided behavior. Decreased metabolism in the posterior medial network might explain the impairment of episodic memory observed during the acute stage of transient global amnesia. Concomitant increased metabolism within the anterior temporal network might occur as a compensatory mechanism.

EFFECT OF COCHLEAR IMPLANTATION ON COGNITIVE FUNCTION: A PRELIMINARY STUDY USING NONVERBAL COMMUNICATION

N 46 28 11 48 22 11 Leeftijd 65.7 (9.2) 61.7 (10.5) 65.6 (7.5) 58.4 (8.4) 65.1 (8.7 ) 62.7 (11.0) 0.003 MMSE 20.9 (5.9) 24.1 (5.1) 23.5 (3.7) 26.5 (2.8) 22.8 (4.6) 21.8 (4.3) <0.001 Sex, female (%) 15 (33) 9 (32) 5 (46) 16 (33) 7 (32) 7 (64) 0.139 Presence Delusions (%) 10 (22) 10 (36) 2 (18) 13 (28) 3 (14) 3 (27) 0.552 Presence Hallucinations (%) 4 (9) 4 (14) 5 (45) 8 (17) 2 (9) 2 (18) 0.070 Presence Agitation/aggression (%) 12 (26) 16 (57) 3 (27) 20 (42) 9 (41) 5 (46) 0.151 Presence Depression/dysphoria (%) 22 (48) 9 (32) 7 (64) 37 (77)* 11 (50) 9 (82)* 0.001 Presence Anxiety (%) 18 (39) 11 (39) 2 (18) 18 (38) 5 (23) 4 (36) 0.618 Presence Elation/euphoria (%) 11 (24) 9 (32) 3 (27) 9 (19) 7 (32) 2 (18) 0.776 Presence Apathy/indifference (%) 24 (52) 25 (89)* 6 (55) 27 (57) 13 (59) 5 (46) 0.029 Presence Disinhibition (%) 16 (35) 19 (68)* 2 (18) 22 (47) 7 (32) 3 (27) 0.018 Presence Irritability/lability (%) 22 (48) 17 (61) 7 (64) 30 (64) 10 (46) 8 (73) 0.400 Presence Aberrant motor behavior (%) 11 (24) 9 (32) 4 (40) 12 (26) 8 (36) 3 (27) 0.824 Presence sleep problems (%) 10 (24) 12 (43) 4 (40) 25 (54) 8 (36) 5 (46) 0.115 Presence Appetite and eating disorders (%) 22 (48) 19 (68) 6 (55) 18 (39) 14 (64) 5(46) 0.182

Transient Global Amnesia Deteriorates the Network Efficiency of the Theta Band

Acute perturbation of the hippocampus, one of the connector hubs in the brain, is a key step in the pathophysiological cascade of transient global amnesia (TGA). We tested the hypothesis that network efficiency, meaning the efficiency of information exchange over a network, is impaired during the acute stage of TGA. Graph theoretical analysis was applied to resting-state EEG data collected from 21 patients with TGA. The EEG data were obtained twice, once during the acute stage (< 24 hours after symptom onset) and once during the resolved stage (> 2 months after symptom onset) of TGA. Characteristic path lengths and clustering coefficients of functional networks constructed using phase-locking values were computed and normalized as a function of the degree in the delta, theta, alpha, beta 1, beta 2 and gamma frequency bands of the EEG. We investigated whether the normalized characteristic path length (nCPL) and normalized clustering coefficients (nCC) differed significantly between the acute and resolved stages of TGA at each frequency band using the Wilcoxon signed-rank test. For networks where the nCPL or nCC differed significantly between the two stages, we also evaluated changes in the connections of the brain networks. During the acute stage of TGA, the nCPL of the theta band networks with mean degrees of 8, 8.5, 9 and 9.5 significantly increased (P < 0.05). During the acute stage, the lost edges for these networks were mostly found between the anterior (frontal and anterior temporal) and posterior (parieto-occipital and posterior temporal) brain regions, whereas newly developed edges were primarily found between the left and right frontotemporal regions. The nCC of the theta band with a mean degree of 5.5 significantly decreased during the acute stage (P < 0.05). Our results indicate that TGA deteriorates the network efficiency of the theta frequency band. This effect might be related to the desynchronization between the anterior and posterior brain areas.

Neurosyphilis Mimicking Creutzfeldt-Jakob Disease

Background As rapidly progressive dementia (RPD), general paresis and Creutzfeldt-Jakob disease (CJD) may have overlapping clinical presentation due to a wide variety of clinical manifestations. Case Report A 57-year-old man presented with rapid progressive cognitive decline, behavioral change, ataxic gait, tremor and pyramidal signs for 3 months. In addition to these multiple systemic involvements, positive result for the cerebrospinal fluid (CSF) 14-3-3 protein tentatively diagnosed him as probable CJD. However, due to increased serum rapid plasma reagin, venereal disease research laboratory, and fluorescent treponemal antibody-absorption reactivity in CSF, the final diagnosis was changed to general paresis. Conclusions A patient with RPD needs to be carefully considered for differential diagnosis, among a long list of diseases. It is important to rule out CJD, which is the most frequent in RPD and is a fatal disease with no cure. Diagnostic criteria or marker of CJD, such as 14-3-3 protein, may be inconclusive, and a typical pattern in diffusion-weighted imaging is important to rule out other reversible diseases.