With increased age, some individuals experience cognitive declines that are more severe than what is observed in healthy cognitive aging. This decline may be related to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Much of the current research on dementia attempts to detect subtle cognitive and memory declines before behavioral and cognitive symptoms are more apparent. Intense research interest has focused on MCI, a condition that includes impairment in some areas of cognitive functioning but is not severe enough to warrant the diagnosis of dementia. MCI may represent a transitional stage between healthy aging and AD and is considered a risk factor for AD development. The purpose of the present thesis was to examine if EEG and ERPs can be used as reliable predictors of cognitive changes in aging and MCI. Study 1 was designed to examine if there is evidence of changes in the EEG between cognitively healthy older adults and people with MCI. The purpose of this study was to examine differences in EEG activity between healthy older adults and people with MCI during early and late portions of a longer-than-normal resting-state recording. Resting state recordings typically last 1-3 minutes. It would be advantageous to run a longer testing session because this would provide more data, but such a procedure might be problematic because it might result in increased drowsiness in the latter half of testing. If this drowsiness affected those with MCI more than healthy adults, this might produce artifactual differences between groups. If increased drowsiness occurs as the duration of the recording becomes longer, an increase of low-frequency EEG activity should be observed, particularly in the delta band. Resting state EEG was recorded in 20 healthy older adults and 20 people with MCI who rested with their eyes closed. The EEG recording was divided into two three-minute halves. People with MCI exhibited a significant increase in theta power density over posterior regions of the scalp compared to healthy older adults. Power density for all frequency bands did not change over the two halves of the recording. That is, there was little evidence of drowsiness in the second half of the recording. Taken together, these findings indicate that longer resting-state EEG recording can be reliably employed without increased risk of drowsiness. Study 2 examined whether there is evidence of a dysfunction in the salience network in older adults. Previous research suggests that older adults may be less able to compute the level of salience of unattended stimulus inputs. The transient detector system is a specialized network of brain areas for detecting sudden changes in the intensity of an auditory stimulus. The output of this system, as reflected by the auditory ERP components N1 and P2, provides a measure of the level of salience of the stimulus. Twenty younger adults and healthy older adults participated in this study. A single auditory stimulus was presented rapidly, every 1.5 s, or very slowly, every 12 s, in different conditions. When the stimuli were presented rapidly, group differences were not observed for the amplitudes of N1 and P2, peaking at 100 and 180 ms, respectively. When stimuli were presented very slowly, their amplitudes were greatly enhanced for younger adults but did not increase for older adults. The failure to observe a large increase in the amplitude of N1 and P2 in older adults for very slowly presented stimuli provides strong evidence of a dysfunction of the salience network in this group. There is evidence that both the functioning of salience network and the frontoparietal network deteriorate in cognitively healthy older adults. These networks might further deteriorate in people with MCI. In study 2, when stimuli were presented slowly, the P2 was delayed and peaked at a time that is more consistent with a P3a. The P3a is elicited by a potentially highly salient, but unattended stimulus input that interrupts the functioning of the frontoparietal network, resulting in a switch of processing priorities away from current task demands and toward the processing of the stimulus input. In study 3, auditory stimuli were again presented either rapidly or very slowly to 20 healthy older adults and 20 people with MCI. The amplitude of N1 did not differ between the two groups in either the fast or slow conditions. Thus, there is little evidence that people with MCI have a deficit in computing the salience of unattended auditory stimuli. When stimuli were presented slowly, the P2/P3a was significantly smaller in people with MCI compared to healthy older adults. The attenuated P2/P3a in people with MCI may reflect a reduced frontoparietal ability to determine processing priorities. In people with MCI, priority of processing may not be switched from the ongoing cognitive task to the potentially much more relevant auditory input. In the results of studies 2 and 3, there was ambiguity regarding whether the positivity observed in the slow condition reflected P2 or P3a activity. A more definite P3a had been elicited in oddball paradigms. In the oddball paradigm, the participant is presented with a sequence of frequently presented homogenous standard stimuli. At rare and unpredictable times, a deviant is presented, the deviant representing a change in a feature of the standard. Deviants that represent a large change from the standard may elicit a P3a. Two experiments were run in which at least one of the deviants had previously been shown to elicit a large P3a in younger adults. Study 4 consisted of two experiments. In Experiment 1, the deviants represented either decreases or increases in the intensity of the standard. The deviant that represented an increase in intensity has been found to elicit a large P3a in previous studies. In Experiment 2, six different deviants were presented. The deviants included a white noise burst and environmental sounds, both of which have elicited a large P3a in previous studies. Across both experiments, the MMN/DRN and P3a did not differ between healthy older adults and people with MCI. Previous studies have indicated that the P3a is reduced in amplitude in healthy older adults compared to younger adults. The results of study 4 indicate that the P3a was not further reduced in people with MCI. This is in contrast to study 3 in which the P2/P3a was reduced in people with MCI. This could be because of the use of the oddball paradigm in study 4. Detection of the deviant would be carried out, at least in part, by the change detection system while in study 3, the presentation of a single stimulus would have been detected only by the transient detection system. Operations of the frontoparietal network controlling processing priorities can be interrupted by sufficient output from either the transient or change detector systems. This results in a switch of processing from an ongoing task to the processing of the potentially more relevant stimulus input. When this interrupt is sent from the change detection system, the operations of the frontoparietal network do not appear to deteriorate in people with MCI compared to what is observed in cognitively healthy older adults.

<p>Lindrig kognitiv störning (eng. Mild Cognitive Impairment, MCI) betecknar ett tillstånd av försämrad kognitiv funktion, som inte uppfyller kriterierna för demens. MCI tycks innebära en ökad risk att utveckla Alzheimer och andra demenssjukdomar. Syftet med studien var att förutsättningslöst undersöka antal och typer av subgrupper till MCI som bäst överensstämmer med kognitiva testresultat samt att undersöka utvecklingsförlopp för subgrupperna. En klusteranalys utfördes med testresultat från 287 MCI patienter som utretts på Huddinge sjukhus. Fyra kluster bildades, ett med normal kognitiv funktion (n=114), ett med episodminnesstörning (n=76), ett med språkstörning (n=55) och ett med spatial störning (n=42). Resultatet överensstämmer inte med tidigare föreslagna subgrupper. Att det bildades ett kluster, vars testresultat visade på en normal kognitiv funktion tyder på brister i diagnostiseringen. Detta kluster hade också en låg konverteringstakt till demenssjukdomar och en stor andel förbättrades kognitivt. Övriga kluster hade ungefär samma konverteringstakt till demens sjukdomar.</p>

Lindrig kognitiv störning (eng. Mild Cognitive Impairment, MCI) betecknar ett tillstånd av försämrad kognitiv funktion, som inte uppfyller kriterierna för demens. MCI tycks innebära en ökad risk att utveckla Alzheimer och andra demenssjukdomar. Syftet med studien var att förutsättningslöst undersöka antal och typer av subgrupper till MCI som bäst överensstämmer med kognitiva testresultat samt att undersöka utvecklingsförlopp för subgrupperna. En klusteranalys utfördes med testresultat från 287 MCI patienter som utretts på Huddinge sjukhus. Fyra kluster bildades, ett med normal kognitiv funktion (n=114), ett med episodminnesstörning (n=76), ett med språkstörning (n=55) och ett med spatial störning (n=42). Resultatet överensstämmer inte med tidigare föreslagna subgrupper. Att det bildades ett kluster, vars testresultat visade på en normal kognitiv funktion tyder på brister i diagnostiseringen. Detta kluster hade också en låg konverteringstakt till demenssjukdomar och en stor andel förbättrades kognitivt. Övriga kluster hade ungefär samma konverteringstakt till demens sjukdomar.

OBJECTIVE: To assess the involvement of the white matter of the brain in the pathology of Alzheimer’s disease. Using Neurite Orientation Density and Dispersion Imaging (NODDI) and the probabilistic white matter parcellation tool Tracula as a means for understanding whether alterations in the white matter underlie changes in perceived cognitive abilities across the spectrum from health aging to Alzheimer’s disease. METHOD: Data were obtained from 28 participants in the Health Outreach Program for the Elderly (HOPE) at the Boston University Alzheimer’s Disease Center (BU ADC) Clinical Core Registry. MRI scans included an MPRAGE T1 scan, multi-b shell diffusion scan and a High Angular Resolution Diffusion Imaging scan (HARDI). Scans were processed with Freesurfer v6.0 and the NODDI Python2.7 toolkit. The resulting data included the orientation dispersion index (ODI) and Fractional Anisotropy (FA) values for cortical and subcortical regions in the DKT atlas space as well as specific Tracts Constrained by Underlying Anatomy (TRACULA) measurements for 18 specific established white matter tracts. Statistical models using measures of pathway integrity (FA and ODI data) were used to assess relationships with Informant Cognitive Change Index (ICCI), self-described Cognitive Change Index (CCI), and Clinical Dementia Rating (CDR) values. RESULTS: Measures of white matter integrity within several tracts predicted ICCI and CDR well in statistical models. FA and ODI values of the bilateral superior longitudinal fasciculi, inferior longitudinal fasciculi, and the cingulum bundle tracts were all related to ICCI and CDR. None of the known tracts’ FA or ODI values were related to CCI. CONCLUSIONS: Measures of white matter pathway integrity were predictive of ICCI and CDR scores but not CCI. These finding support the notion that self-report of cognitive abilities may be compromised by alterations in insight and reinforce the need for informed study partners and clinical ratings to evaluate potential MCI and AD.

Emerging research has suggested that the nature of cognitive deficits in Amnestic-MCI (a-MCI) may extend beyond memory impairments and can include deficits in attention (Gualtieri & Johnson, 2005; 2007). Recent studies have found significant differences between subjects with a-MCI and cognitively healthy individuals on measures of processing speed (Gorus, De Raedt, Lambert, Lemper, & Mets, 2008; Gualtieri & Johnson, 2005; Levinoff, Saumier, & Chertkow, 2005; Silveri et al., 2007). The current study sought to add to the limited research currently available on processing speed in a-MCI by comparing cognitively healthy individuals (M age = 64.57; SD = 6.61) and an age-matched a-MCI group (M age = 64.19; SD = 5.79) on a measure of processing speed, an index of attention. Second, the study evaluated the utility of the “25 Numbers Test” in differentiating individuals with a-MCI from a cognitively healthy group of participants. As expected, the participants with a-MCI performed more poorly (t(72) = -5.96, p < .01) on the 25 Numbers Test and demonstrated greater intra-individual variability in comparison to the cognitively healthy group (t(72) = -3.009, p < .01). The 25 Numbers Test effectively discriminated cognitively healthy individuals from those with a-MCI (AUC = 0.85, p < .01). Results will add to the limited research on processing speed in a-MCI and provide a basis for the importance of evaluating processing speed as part of routine screening for a-MCI.

Ce travail doctoral a pour premier objectif de replacer les démences dans leur contexte de santé publique en estimant des projections de nombre de cas de démences en France et en Europe jusqu'en 2050. La sensibilité de ces projections aux changements d'hypothèses sur les valeurs d'incidence ou de mortalité des sujets déments, sur le scenario démographique utilisé, et sur la mise en place d'une intervention de prévention, a également été évaluée. Dans ce contexte de forte augmentation du nombre de cas à venir, la prévention des démences, qu'elle soit primaire ou secondaire, sera amenée à tenir une place primordiale dans la prise en charge sociétale de ce problème. Pour pouvoir aboutir à des résultats, les recherches en prévention primaire et secondaire ont besoin de s'appuyer sur une méthodologie adaptée et de sélectionner des critères de jugements pertinents. Le déclin cognitif semble être un critère de jugement de choix, mais son l'utilisation doit éviter un certain nombre d'écueils et de biais. Nous avons dans un premier temps illustré l'analyse de ce critère dans le cadre d'un questionnement de prévention primaire à l'aide d'un modèle non linéaire à variable latente pour données longitudinales. Nous avons pour cela étudié la relation entre consommation chronique de benzodiazépines et déclin cognitif, et montré l'absence d'association sur un large échantillon. Dans un second temps nous avons utilisé ce type de modèle pour décrire et comparer les propriétés métrologiques d'un large ensemble de tests neuropsychologiques dans une cohorte clinique de sujets atteints de déficit cognitif modéré (MCI), et pour étudier la sensibilité de ces tests aux changements cognitifs lié aux prodromes de la maladie d'Alzheimer. Nos travaux ont ainsi permis de fournir des arguments permettant de sélectionner des tests neuropsychologiques susceptibles d'être utilisés dans le cadre de recherches de prévention secondaire pour identifier et/ou suivre les patients présentant un déficit cognitif modéré (MCI) lié à une maladie d'Alzheimer. / The first aim of this doctoral work is to replace dementia in its public health context by estimating the number of dementia cases expected to occur in France and Europe over the next few decades until 2050. The sensitivity of these projections to hypotheses made on dementia incidence and mortality, demographic scenario used, and implementation of a prevention intervention, was also assessed. In this context of increasing number of future cases, the primary and secondary prevention of dementia will take a prominent place in the social management of this problem. Relevant research in the field of primary and secondary prevention requires an appropriate methodology and the use of relevant outcome. Cognitive decline seems to be an appropriate outcome, but a number of biases must be avoided. First, we illustrated the use of this criterion in the context of primary prevention using a nonlinear model with latent variable for longitudinal data to investigated the association between chronic use of benzodiazepines and cognitive decline. We showed the absence of association in a large population-based cohort. Secondly we used this model to describe and compare the metrological properties of a broad range of neuropsychological tests in a clinical cohort of patients with mild cognitive impairment (MCI). We also investigated the sensitivity of these tests to cognitive changes associated with prodromal Alzheimer's disease. Our work provides arguments for selecting neuropsychological tests which can be used in secondary prevention research, to identify and / or to follow patients with mild cognitive impairment (MCI) due to Alzheimer's disease.

Les personnes atteintes de troubles cognitifs légers (i.e., Mild Cognitive Impairment, MCI) souffrent d’un déclin cognitif, pouvant engendrer des troubles exécutifs et fonctionnels, pénalisants dans leurs activités de la vie quotidienne. Face à ces déficits, plusieurs programmes d’intervention de stimulations physique ou cognitive montrent des résultats encourageants sur les performances de ces profils. / People with Mild Cognitive Impairment (MCI) suffer from a cognitive decline, which engender executive and functional disorders, punishing in their activities of the everyday life. Given these deficits, several programs of physical or cognitive stimulations show encouraging results on cognitive performances of these profiles.

Bakgrund: Antalet äldre i världen ökar ständigt. Åtta procent av Sveriges befolkning, som är 65 år och äldre, har någon form av kognitiv svikt. Med åldern ökar risken för mild kognitiv svikt, vilket påverkar alla områden i människans liv. Mild kognitiv svikt är ett tillstånd som kan leda till mer omfattande kognitiv nedsättning om det inte åtgärdas i ett tidigt skede. Det är därför viktigt att tidigt upptäcka och åtgärda de första symtomen på mild kognitiv svikt.  Syfte: Syftet med studien var att undersöka vilka interventioner som kan förbättra livskvaliteten hos äldre personer med mild kognitiv svikt. Metod: Systematisk blandad litteratur översikt (Systematic mixed studie review) med narrativ sammanfattning (narrativ summary) enligt Ryan (2013) valdes som studiedesign. Artiklar söktes systematiskt i databaserna Cinahl, PubMed och PsycINFO. Följande kategorier fastställdes vid analysen: fysisk aktivitet, kognitiv stimulans, kombinerade fysiska och kognitionsstimulerande interventioner och estetiska aktiviteter. Resultat: Studiens resultat baserades på en analys av elva kvantitativa och tre kvalitativa studier som omfattade äldre personer i ålder 65+ med MCI. Dessa artiklar publicerades mellan åren 2019 och 2023 och omfattade länderna Italien (1), Kanada (1), Kina (6), Mexiko (1), Nederländerna (1), Sverige (1), Tyskland (1) och USA (2). Interventioner som inkluderades i studien omfattade: fysiska aktiviteter som Tai Chi, måttlig aerob träning och squaredans; interventioner för kognitiv stimulans med hjälp av modern teknink; fysiska aktiviteter kombinerade med kognitiv träning; samt estetiska aktiviteter som stråkkonst, akvarell och akrylmålning. Interventionerna visade varierande grad av påverkan på livskvalitet för äldre personer med MCI, men samtliga visade positiv effekt på livskvaliteten. Slutsatser: Det finns evidens som tyder på att användandet av moderna teknologier kan förbättra äldre personernas med MCI livskvalitet. Interventioner som mindfulness, reminiscens, estetiska och fysiska aktiviteter kan också ge en positiv effekt på livskvalitet hos äldre personer med MCI. / Background: The number of elderly people in the world is constantly increasing. Eight percent of Sweden's population, who are 65 years and older, have some form of cognitive impairment. With age, the risk of mild cognitive impairment increases, which affects all areas of a person's life. Mild cognitive impairment is a condition that can lead to more extensive cognitive impairment if not addressed in its early stages. It is therefore important to detect and address the first symptoms of mild cognitive impairment at an early stage.  Aim: The aim of this study was to investigate which interventions can improve the quality of life in older people with mild cognitive impairment. Method: Systematic mixed study review with narrative summary according to Ryan (2013) was chosen as the study design. Articles were systematically searched in the databases Cinahl, PubMed and PsycINFO. The following categories were established in the analysis: physical activity, cognitive stimulation, combined physical and cognition-stimulating interventions, and aesthetic activities. Results: The results of the study were based on an analysis of eleven quantitative and three qualitative studies that included older people aged 65+ with MCI. These articles were published between the years 2019 and 2023 and covered the countries Italy (1), Canada (1), China (6), Mexico (1), the Netherlands (1), Sweden (1) Germany (1), and the United States (2). Interventions in the study included: physical activities such as Tai Chi, moderate aerobic, and square dancing; interventions for cognitive stimulation using modern technology; physical activities combined with cognitive training; as well as aesthetic activities such as string art, watercolor, and acrylic painting. The interventions showed varying degrees of impact on quality of life for older people with MCI, but all showed a positive effect on quality of life.  Conclusions: There is evidence to suggest that the use of modern technologies can improve the quality of life of older people with MCI. Interventions such as mindfulness, reminiscence, aesthetic and physical activities can also have a positive effect on quality of life in older people with MCI.

<p>Lindrig kognitiv störning (eng. mild cognitive impairment, MCI) är en term som började användas på 1990-talet för att benämna personer med kognitiva tillstånd i gränsområdet mellan normalt fungerande och demens. Syftet med MCI-forskningen är att identifiera individer med demenssjukdom i ett mycket tidigt skede av sjukdomen för att i framtiden kunna sätta in behandling tidigare än idag. I longitudinella studier har det visat sig att personer med MCI inom några år antingen försämras kognitivt (med eller utan demens), förbättras kognitivt, eller förblir stabila i kognitiv funktion. Vid ett konsensusmöte 2003 föreslogs fyra subgrupper av MCI. Syftet med föreliggande studie var att subgruppera 245 patienter som utretts vid minnesklinik med diagnosen MCI. Subgrupperingen gjordes utifrån resultat på kognitiva funktionstest, vilka tillsammans med medicinska undersökningsresultat hämtades ur databasen GEDOC, Karolinska universitetssjukhuset. Den största gruppen patienter placerades i subgrupp 3 (MCI med episodminnesstörning samt störning i en eller flera andra kognitiva domäner). Eventuella samband mellan typ av kognitiv funktionsnedsättning och medicinska riskfaktorer undersöktes med envägs (4 grupper) ANOVA respektive chi-två och signifikans erhölls för utbildning, LDL-blodfett och nedsatt sköldkörtelfunktion. Denna studie berör ett forskningsmässigt relativt outforskat område då tidigare studier främst har jämfört personer med MCI med normala medan föreliggande studie jämförde personer med olika typ av MCI med varandra. Ytterligare studier behövs för att avgöra om denna subgruppering är kliniskt relevant.</p>

Lindrig kognitiv störning (eng. mild cognitive impairment, MCI) är en term som började användas på 1990-talet för att benämna personer med kognitiva tillstånd i gränsområdet mellan normalt fungerande och demens. Syftet med MCI-forskningen är att identifiera individer med demenssjukdom i ett mycket tidigt skede av sjukdomen för att i framtiden kunna sätta in behandling tidigare än idag. I longitudinella studier har det visat sig att personer med MCI inom några år antingen försämras kognitivt (med eller utan demens), förbättras kognitivt, eller förblir stabila i kognitiv funktion. Vid ett konsensusmöte 2003 föreslogs fyra subgrupper av MCI. Syftet med föreliggande studie var att subgruppera 245 patienter som utretts vid minnesklinik med diagnosen MCI. Subgrupperingen gjordes utifrån resultat på kognitiva funktionstest, vilka tillsammans med medicinska undersökningsresultat hämtades ur databasen GEDOC, Karolinska universitetssjukhuset. Den största gruppen patienter placerades i subgrupp 3 (MCI med episodminnesstörning samt störning i en eller flera andra kognitiva domäner). Eventuella samband mellan typ av kognitiv funktionsnedsättning och medicinska riskfaktorer undersöktes med envägs (4 grupper) ANOVA respektive chi-två och signifikans erhölls för utbildning, LDL-blodfett och nedsatt sköldkörtelfunktion. Denna studie berör ett forskningsmässigt relativt outforskat område då tidigare studier främst har jämfört personer med MCI med normala medan föreliggande studie jämförde personer med olika typ av MCI med varandra. Ytterligare studier behövs för att avgöra om denna subgruppering är kliniskt relevant.