Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (<i>MTCO II</i>) in blood samples from probable AD Mexican patients. <i>MTCO II</i> gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12&#x25;) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn&#x2019;t been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.

Ver&#xf3;nica Loera-Casta&#xf1;eda

Lucila Sandoval-Ram&#xed;rez

Ferm&#xed;n Paul Pacheco Mois&#xe9;s

Miguel &#xc1;ngel Mac&#xed;as-Islas

Mois&#xe9;s Alejandro Alatorre Jim&#xe9;nez

Erika Daniela Gonz&#xe1;lez-Renovato

Fernando Cort&#xe9;s-Enr&#xed;quez

Alfredo C&#xe9;lis de la Rosa

Irma E. Vel&#xe1;zquez-Brizuela

Genaro Gabriel Ortiz

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

<i>Background</i>. Given the dementia epidemic and the increasing cost of healthcare, there is a need to assess the economic benefit of community based dementia screening programs. <i>Materials and Methods</i>. Markov model simulations were generated using data obtained from a community based dementia screening program over a one-year period. The models simulated yearly costs of caring for patients based on clinical transitions beginning in pre dementia and extending for 10 years. <i>Results</i>. A total of 93 individuals (74 female, 19 male) were screened for dementia and 12 meeting clinical criteria for either mild cognitive impairment <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.18977pt" id="M1" height="11.4781pt" version="1.1" viewBox="-0.0498162 -9.28833 38.3889 11.4781" width="38.3889pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g50-41" d="M309 -142C211 -61 151 99 151 271S210 601 309 683L288 710C141 611 75 451 75 272V271C75 90 141 -72 288 -169L309 -142Z"/></g><g transform="matrix(.013,0,0,-0.013,4.654,0)"><path id="g58-108" d="M532 0V30C473 38 467 38 467 107V298C467 395 416 451 336 451C307 451 279 439 251 420C226 404 205 389 185 374V453C142 434 94 422 43 413V386C98 378 104 373 104 309V107C104 41 100 38 31 30V0H251V30C191 35 185 40 185 107V337C216 364 255 389 295 389C360 389 386 347 386 276V110C386 44 380 35 321 30V0H532Z"/></g><g transform="matrix(.013,0,0,-0.013,15.615,0)"><path id="g54-34" d="M556 331V384H55V331H556ZM556 140V193H55V140H556Z"/></g><g transform="matrix(.013,0,0,-0.013,27.233,0)"><path id="g50-56" d="M453 623H65C60 580 56 530 46 472H80C103 538 110 548 175 548H389C310 380 195 168 90 0L98 -12L175 -2C273 206 366 408 462 610L453 623Z"/></g><g transform="matrix(.013,0,0,-0.013,33.566,0)"><path id="g50-42" d="M283 271C283 451 220 610 70 710L48 683C146 603 207 443 207 271S149 -59 48 -142L70 -169C220 -67 283 90 283 271Z"/></g></svg> or dementia <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.18977pt" id="M2" height="11.4781pt" version="1.1" viewBox="-0.0498162 -9.28833 38.3889 11.4781" width="38.3889pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g50-41"/></g><g transform="matrix(.013,0,0,-0.013,4.654,0)"><use xlink:href="#g58-108"/></g><g transform="matrix(.013,0,0,-0.013,15.615,0)"><use xlink:href="#g54-34"/></g><g transform="matrix(.013,0,0,-0.013,27.233,0)"><path id="g50-54" d="M158 548H390L417 615L410 623H122L83 318C105 326 143 337 185 337C296 337 350 275 350 188C350 116 308 42 225 42C164 42 122 74 100 93C90 101 82 99 72 92C60 82 51 68 50 59C48 46 52 38 66 24C82 9 125 -12 172 -12C225 -11 292 15 346 59C408 108 437 166 437 226C437 309 371 397 242 397C214 397 170 382 133 369L158 548Z"/></g><g transform="matrix(.013,0,0,-0.013,33.564,0)"><use xlink:href="#g50-42"/></g></svg> were identified. Assuming early therapeutic intervention beginning during the year of dementia detection, Markov model simulations demonstrated 9.8&#x25; reduction in cost of dementia care over a ten-year simulation period, primarily through increased duration in mild stages and reduced time in more costly moderate and severe stages. <i>Discussion</i>. Community based dementia screening can reduce healthcare costs associated with caring for demented individuals through earlier detection and treatment, resulting in proportionately reduced time in more costly advanced stages.

Erin Saito

Beau K. Nakamoto

Mario F. Mendez

Bijal Mehta

Aaron McMurtray

Cost Effective Community Based Dementia Screening: A Markov Model Simulation

A number of recent studies have reported that working memory does not seem to show typical age-related deficits in healthy older adults when emotional information is involved. Differently, studies about the short-term ability to encode and actively manipulate emotional information in dementia of Alzheimer&#x2019;s type are few and have yielded mixed results. Here, we review behavioural and neuroimaging evidence that points to a complex interaction between emotion modulation and working memory in Alzheimer&#x2019;s. In fact, depending on the function involved, patients may or may not show an emotional benefit in their working memory performance. In addition, this benefit is not always clearly biased (e.g., towards negative or positive information). We interpret this complex pattern of results as a consequence of the interaction between multiple factors including the severity of Alzheimer&#x2019;s disease, the nature of affective stimuli, and type of working memory task.

Nicola Mammarella

Beth Fairfield

Emotional Working Memory and Alzheimer&#x2019;s Disease

<i>Background</i>. Amnestic Mild Cognitive Impairment (aMCI) often progresses to Alzheimer&#x2019;s disease. There are clinical markers and biomarkers to identify the degenerative process in the brain. <i>Objectives</i>. To obtain the diagnostic values of olfactory test, pupillary response to tropicamide 0.01&#x25;, BDNF plasma level, and APOE <i>&#x3B5;</i>4 in diagnosing aMCI. <i>Methods</i>. Cross-sectional, comparative analysis. <i>Results</i>. There were 109 subjects enrolled (aMCI: 51, normal cognition: 58) with age 64&#x2009;&#xb1;&#x2009;5.54 years. For diagnosing aMCI, cut-off point for the olfactory score was &#x3C;7 out of 10 and &#x3e;22&#x25; for pupil dilatation response. Low BDNF plasma level was related significantly with olfactory deficits and aMCI (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.1625795pt" id="M1" height="8.9689pt" version="1.1" viewBox="0 -8.80632 45.8219 8.9689" width="45.8219pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,30.391,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>). Four of five subjects with homozygote e4 presented with multiple-domain aMCI. This group displayed the lowest means of olfactory score and the highest means of pupillary hypersensitivity response (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.1625795pt" id="M2" height="8.9689pt" version="1.1" viewBox="0 -8.80632 58.1914 8.9689" width="58.1914pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.391,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,52.989,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>). Combination of olfactory deficit and pupillary hypersensitivity response in detection of aMCI was beneficial with Sp 91&#x25; and PPV 87&#x25;. In conjunction with clinical markers, BDNF plasma level and presence of APOE e4+ improved Sp and PPV. <i>Conclusions</i>. Combination of olfactory test and pupillary response test was useful as diagnostic tool in aMCI. In conjunction with clinical markers, low level of BDNF plasma and presence of APOE e4 improved the diagnostic value.

Yuda Turana

Teguh Asaat S. Ranakusuma

Jan Sudir Purba

Nurmiati Amir

Siti Airiza Ahmad

Moh. Hasan Machfoed

Yvonne Suzy Handayani

Asmarinah

Sarwono Waspadji

Enhancing Diagnostic Accuracy of aMCI in the Elderly: Combination of Olfactory Test, Pupillary Response Test, BDNF Plasma Level, and APOE Genotype

Neprilysin (NEP) is the principal amyloid <i>β</i> (A<i>β</i>) degrading peptidase; this activity may protect against Alzheimer’s disease (AD), the most important age-related neurodegenerative process. The aim of this work was to analyze NEP mRNA expression in the frontal cortex of dogs with and without canine cognitive dysfunction syndrome (CDS), which is considered a natural model for AD. Expression of canine cerebral NEP mRNA was assessed by RT-PCR followed by qPCR in young, aged-cognitively unimpaired (CU), and aged-cognitively impaired (CI) dogs. On average, aged-CI dogs showed 80% (<svg style="vertical-align:-0.1638pt;width:58.712502px;" id="M1" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30" /></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g></svg>) lower expression levels of NEP mRNA than their aged-CU counterparts. Furthermore, the standard deviation of the qPCR measurements was more than 6 times higher in the cognitively healthy animals (young and aged-CU) than in the aged-CI group. Another interesting find is the determination of a positive correlation between NEP expression and the number of cholinergic neurons in basal telencephalon, indicating a probable connection between both events in these types of neurodegeneration processes. These results suggest that high expression levels of NEP might be a protective factor for canine CDS and, most likely, for other A<i>β</i>-associated neurodegenerative diseases, such as AD.

Jes&#xfa;s Canudas

Daniel Insua

Leticia Sarasa

&#xc1;ngela Gonz&#xe1;lez-Mart&#xed;nez

Mar&#xed;a Luisa Su&#xe1;rez

Germ&#xe1;n Santamarina

Pedro Pesini

Manuel Sarasa

Neprilysin Is Poorly Expressed in the Prefrontal Cortex of Aged Dogs with Cognitive Dysfunction Syndrome

To evaluate the hypothesis that quantitative EEG (qEEG) analysis is susceptible to detect early functional changes in familial Alzheimer's disease (AD) preclinical stages. Three groups of subjects were selected from five extended families with hereditary AD: a Probable AD group (18 subjects), an asymptomatic carrier (ACr) group (21 subjects), with the mutation but without any clinical symptoms of dementia, and a normal group of 18 healthy subjects. In order to reveal significant differences in the spectral parameter, the Mahalanobis distance (<svg     style="vertical-align:-0.0pt;width:20.112499px;" id="M1" height="15.8375" version="1.1" viewBox="0 0 20.112499 15.8375" width="20.112499"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,15.775)"><path id="x1D437" d="M780 372q0 -191 -178 -297q-128 -75 -335 -75h-250l7 27q61 7 77 22t28 76l77 398q11 62 0 76.5t-77 22.5l6 28h292q164 0 258.5 -67.5t94.5 -210.5zM678 375q0 119 -73 180.5t-201 61.5q-62 0 -82 -13q-17 -7 -25 -53l-80 -427q-8 -47 -4 -62t26 -20q24 -6 80 -6&#xA;q166 0 262.5 95t96.5 244z" /></g>

			<g transform="matrix(.012,-0,0,-.012,13.712,7.613)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g>

		
	
</svg>) was calculated between groups. To evaluate the diagnostic efficiency of this statistic <svg     style="vertical-align:-0.0pt;width:20.112499px;" id="M2" height="15.8375" version="1.1" viewBox="0 0 20.112499 15.8375" width="20.112499"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,15.775)"><use xlink:href="#x1D437"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.712,7.613)"><use xlink:href="#x32"/></g>

		
	
</svg>, the ROC models were used. The ROC curve was summarized by accuracy index and standard deviation. The <svg     style="vertical-align:-0.0pt;width:20.112499px;" id="M3" height="15.8375" version="1.1" viewBox="0 0 20.112499 15.8375" width="20.112499"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,15.775)"><use xlink:href="#x1D437"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.712,7.613)"><use xlink:href="#x32"/></g>

		
	
</svg> using the parameters of the energy in the fast frequency bands shows accurate discrimination between normal and ACr groups (area ROC = 0.89) and between AD probable and ACr groups (area ROC = 0.91). This is more significant in temporal regions. Theses parameters could be affected before the onset of the disease, even when cognitive disturbance is not clinically evident. Spectral EEG parameter could be firstly used to evaluate subjects with E280A Presenilin-1 mutation without impairment in cognitive function.

Rene Rodriguez

Francisco Lopera

Alfredo Alvarez

Yuriem Fernandez

Lidice Galan

Yakeel Quiroz

Maria Antonieta Bobes

Spectral Analysis of EEG in Familial Alzheimer&#x2019;s Disease with E280A  Presenilin-1 Mutation Gene

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<p><em>International Journal of Alzheimer’s Disease</em> publishes original research articles and&nbsp;review articles in all areas of Alzheimer's disease.</p>


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International Journal of Alzheimer’s Disease - Table of contents 2014

International Journal of Alzheimer’s Disease | Hindawi

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International Journal of Alzheimer’s Disease publishes original research articles and review articles in all areas of Alzheimer's disease.

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International Journal of Alzheimer’s Disease

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