Regional lobar atrophy predicts memory impairment in multiple sclerosis.

Department of Neurology, SUNY Buffalo School of Medicine, Buffalo, NY 14203, USA.
American Journal of Neuroradiology (Impact Factor: 3.68). 09/2005; 26(7):1824-31.
Source: PubMed

ABSTRACT In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychological testing, explaining more variance than measures of lesion burden in patients with multiple sclerosis. The relationship between regional lobar atrophy and cognitive impairment is yet to be examined. We endeavored to assess the clinical significance of regional lobar atrophy in multiple sclerosis.
In a cross-sectional study, we evaluated 31 patients with multiple sclerosis with brain MR imaging and neuropsychological testing. Impairment was determined by comparison with demographically matched healthy controls. MR imaging generated measures of lesion burden (fluid-attenuated inversion recovery hyperintense volume), general atrophy (brain parenchymal fraction), central atrophy (lateral ventricle volume), and lobar atrophy (regional brain parenchymal fraction of frontal, temporal, parietal, and occipital lobes in each hemisphere). Neuropsychological testing emphasized measures of processing speed and memory, because these are commonly affected in multiple sclerosis.
Patients with multiple sclerosis showed significant atrophy and impairment on all neuropsychological tests. Regional atrophy accounted for the most variance in all regression models predicting memory performance. Left temporal atrophy was the primary predictor of auditory/verbal memory (partial r's = 0.55-0.61), and both left and right temporal atrophy predicted visual/spatial memory performance (partial r's = 0.51-0.67). Models predicting learning consistency retained frontal lobe atrophy measures (partial r's = 0.44-0.68). Central and general atrophy measures were the primary predictors in modeling processing speed (partial r's = 0.42-0.64).
Regional atrophy accounts for more variance than lesion burden, whole brain atrophy, or lateral ventricle volume in predicting multiple sclerosis-associated memory dysfunction.

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    • "Cognitive impairment is among the main symptoms, affecting about half of all MS patients, and lower processing speed and defective retrieval from recent memory storage are frequently observed [4] [5] [6]. Impairment of cognitive functioning is correlated with brain atrophy revealed with MRI [7] [8]. Memory has multiple regional atrophy correlates, including deep gray matter [9], cerebral cortex volume [8], and medial temporal lobe volume [10] [11]. "
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    • "Although some authors claim no close association with physical disability, disease duration or disease course [McIntosh-Michaelis et al. 1991; Rao et al. 1991], others observed it to be more frequent and severe in progressive forms and correlating with the rate of physical disability [Calabrese, 2006]. In general, relapsing–remitting patients suffer less from cognitive impairment than those with chronic progressive illness and among those secondary progressive patients favour a worse picture [Amato et al. 2006c], but even in benign MS without physical disability, cognitive impairment was found in 44% [Benedict et al. 2005]. Cognitive impairment in MS is often a hidden condition and again there is interdependency with depression since it may worsen cognitive functioning just as cognitive dysfunction may induce depression [Sá, 2007], but recent studies were not able to find a correlation between both disorders [Siegert and Abernethy, 2005]. "
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    ABSTRACT: Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, characterized especially by myelin and axon damage. Cognitive impairment in MS is common but difficult to detect without a neuropsychological examination. Valid and reliable methods are needed in clinical practice and research to detect deficits, follow their natural evolution, and verify treatment effects. The Paced Auditory Serial Addition Test (PASAT) is a measure of sustained and divided attention, working memory, and information processing speed, and it is widely used in MS patients neuropsychological evaluation. Additionally, the PASAT is the sole cognitive measure in an assessment tool primarly designed for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). The aims of the present study were to determine a) the frequency, characteristics, and evolution of cognitive impairment among relapsing-remitting MS patients, and b) the validity and reliability of the PASAT in measuring cognitive performance in MS patients. The subjects were 45 relapsing-remitting MS patients from Seinäjoki Central Hospital, Department of Neurology and 48 healthy controls. Both groups underwent comprehensive neuropsychological assessments, including the PASAT, twice in a one-year follow-up, and additionally a sample of 10 patients and controls were evaluated with the PASAT in serial assessments five times in one month. The frequency of cognitive dysfunction among relapsing-remitting MS patients in the present study was 42%. Impairments were characterized especially by slowed information processing speed and memory deficits. During the one-year follow-up, the cognitive performance was relatively stable among MS patients on a group level. However, the practice effects in cognitive tests were less pronounced among MS patients than healthy controls. At an individual level the spectrum of MS patients cognitive deficits was wide in regards to their characteristics, severity, and evolution. The PASAT was moderately accurate in detecting MS-associated cognitive impairment, and 69% of patients were correctly classified as cognitively impaired or unimpaired when comprehensive neuropsychological assessment was used as a "gold standard". Self-reported nervousness and poor arithmetical skills seemed to explain misclassifications. MS-related fatigue was objectively demonstrated as fading performance towards the end of the test. Despite the observed practice effect, the reliability of the PASAT was excellent, and it was sensitive to the cognitive decline taking place during the follow-up in a subgroup of patients. The PASAT can be recommended for use in the neuropsychological assessment of MS patients. The test is fairly sensitive, but less specific; consequently, the reasons for low scores have to be carefully identified before interpreting them as clinically significant. MS-potilaiden kognitiiviset häiriöt ovat yleisiä ja ne tulisi tunnistaa varhain Multippeliskleroosi eli MS-tauti on yleisin nuorten aikuisten vakava neurologinen sairaus, ja sen kansantaloudellinen merkitys on suuri. Kyseessä on parantumaton tulehduksellinen keskushermoston sairaus, joka aiheuttaa sekä valkean että harmaan aineen vaurioita. Kognitiivisen toimintakyvyn, kuten muistin, tarkkaavaisuuden ja tavoitteisen toiminnan säätelyn häiriöt, ovat MS-taudissa yleisiä ja laaja-alaisesti potilaan elämänlaatuun vaikuttavia, mutta ne jäävät usein alidiagnosoiduiksi. Luotettavia kognitiivisen suoriutumisen arviointimenetelmiä tarvitaan niin kliiniseen kuin tutkimustyöhönkin. Paced Auditory Serial Addition Test (PASAT) on numeerinen tarkkaavuuden, työmuistin sekä tiedon käsittelyn nopeuden arviointimenetelmä, jota on yleisesti käytetty MS-potilaiden neuropsykologisessa arvioinnissa. Väitöstutkimuksessa selvitettiin pahenemisvaiheittain etenevää MS-tautia sairastavien potilaiden kognitiivisten häiriöiden yleisyyttä, luonnetta ja etenemistä sekä erityisesti PASAT:n luotettavuutta ja toistettavuutta MS-potilaiden kognitiivisen suoriutumisen arvioinnissa. Tutkimusmenetelminä käytettiin kliinisiä neuropsykologisia testejä. Kognitiivisten häiriöiden yleisyys lievimmät häiriöt mukaan lukien oli tässä tutkimuksessa MS-tautia sairastavilla potilailla 42%. Häiriöille oli luonteenomaista erityisesti tiedon käsittelyn hidastuneisuus sekä muistihäiriöt. Ryhmätasolla MS-potilaiden kognitiivinen suoriutuminen säilyi suhteellisen vakaana vuoden seurannan aikana. Neuropsykologisten testitulosten kohentuminen uusintatutkimuksessa jäi kuitenkin vähäisemmäksi MS-potilailla kuin terveillä kontrolleilla. Yksilötasolla MS-potilaiden kognitiivisten häiriöiden kirjo oli laaja, niin niiden luonteen, vaikeusasteen kuin etenemisenkin osalta. PASAT todettiin kohtuullisen tarkaksi testiksi MS-tautiin liittyvien kognitiivisten häiriöiden tavoittamisessa. Heikot matemaattiset taidot ja testiahdistuneisuus heikensivät myös niiden potilaiden PASAT-tulosta, joilla ei todettu ongelmia kattavassa neuropsykologisessa arviossa. MS-taudille tavanomainen väsyvyys oli objektiivisesti osoitettavissa suoriutumisen heikentymisenä testin loppua kohden. PASAT-tulos koheni toistomittauksissa merkittävästi testioppimisen vuoksi. Tästä huolimatta testin toistettavuus oli erinomainen ja se oli herkkä tavoittamaan osalla potilaista esiintulevan kognitiivisen heikentymisen seurannassa. MS-potilailla varsin yleisesti esiintyvät kognitiiviset häiriöt tulisi havaita varhain, jotta niiden aiheuttamia haittoja voitaisiin vähentää. Neuropsykologinen tutkimus on keskeisin menetelmä MS-potilaiden kognitiivisten muutosten tunnistamiseksi. Väitöstutkimuksen tulosten perusteella PASAT-testin sisällyttämistä voidaan suositella osaksi MS-potilaiden neuropsykologista arviointia. Kuitenkin testitulosten luotettava tulkinta edellyttää testin rajoitusten huomioimista.
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