Predicting Alzheimer's disease development : a comparison of cognitive criteria and associated neuroimaging biomarkers

Introduction: The definition of “objective cognitive impairment” in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer’s disease (AD) from baseline to 24 months. Methods: The sensitivity and specificity of six methods of defining episodic memory impairment (< −1, −1.5 or −2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer’s Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOEε4 status) was investigated using logistic regression. Results: Baseline scores < −1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE ε4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < −1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = −15.97, SE = 7.58, p = .035), and APOEε4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < −2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE ε4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy. Conclusions: Episodic memory impairment in MCI should be defined as scores < −1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE ε4 status can further improve prediction

Symptômes dépressifs et fonctionnement cognitif chez des individus à risque de développer la maladie d’Alzheimer

Compte tenu du nombre grandissant de cas de maladie d'Alzheimer (MA), il est impératif d'accroître notre compréhension de sa phase prodromique. Cette thèse vise à contribuer aux travaux dans ce domaine en caractérisant le fonctionnement cognitif d’individus à risque de développer la MA : ceux avec un trouble cognitif léger amnésique (TCLa), une dépression gériatrique (DEP) et un TCLa avec symptômes dépressifs concomitants (TCLa/D+). Leurs performances sont comparées à celles de participants contrôles (CONT) dans trois expériences. La première explore l’influence de la valence émotionnelle des stimuli sur les performances mnésiques pour des mots positifs, négatifs et neutres. Comparativement aux mots neutres, les CONT et TCLa/D+ rappellent davantage de mots émotionnels (positifs et négatifs), les TCLa rappellent davantage de mots positifs et les DEP rappellent davantage de mots négatifs. Dans la deuxième expérience, l’influence de la valence et de l’intensité émotionnelles des stimuli sur les performances mnésiques est testée à l’aide d’images. Les résultats révèlent une association entre les images émotionnelles et les performances des TCLa et CONT, et entre les images négatives et les performances des TCLa/D+. La valence n'est pas associée au rappel chez les DEP. Par ailleurs, l’intensité émotionnelle des stimuli est positivement associée au rappel d’images positives chez les CONT, et au rappel d’images négatives chez les TCLa/D+ et DEP. L’intensité est négativement associée au rappel d’images positives chez les TCLa. Dans une troisième étude comparant ces groupes sur leurs connaissances sémantiques d’objets biologiques et manufacturés, seuls les TCLa/D+ présentent des déficits, surtout en ce qui concerne les objets biologiques. En revanche, les TCLa et DEP obtiennent des résultats normaux. Globalement, cette thèse démontre que les individus avec TCLa, TCLa/D+ et DEP présentent des caractéristiques distinctes au plan de la mémoire épisodique et de la mémoire sémantique. Les conclusions ont d’importantes retombées théoriques et cliniques. Notamment, elles éclaircissent les caractéristiques sémiologiques de chaque groupe et appuient la notion qu’ils correspondent à des syndromes distinguables sur le plan du fonctionnement cognitif. De plus, les résultats contribuent à clarifier la nosologie du TCLa/D+, ce qui ouvre la voie aux recherches futures sur les traitements adaptés à cette condition.As the prevalence of Alzheimer’s disease (AD) rises in Canada and worldwide, it is imperative to increase our understanding of its prodromal stages. This dissertation contributes to the body of research in this field by exploring the cognitive characteristics of three at-risk groups: those with amnestic mild cognitive impairment (aMCI), late-life depression (LLD) and aMCI with concomitant depressive symptoms (aMCI/D+). The cognitive performance of these groups is compared to that of healthy elderly control subjects (CONT) on three experimental tasks. The first explores the influence of emotional valence on memory for positive, negative and neutral word lists. Results reveal that, compared to neutral words, CONT and aMCI/D+ subjects recall more emotional (positive and negative) words, aMCI subjects recall more positive words, and LLD subjects recall more negative words. The second experiment investigates the effect of valence and intensity on memory for emotional images. Results show that valence is associated with recall of positive and negative images in the aMCI and CONT groups, and with recall of negative images in the aMCI/D+ group. Valence is not associated with recall in the LLD group. In addition, the stimuli’s emotional intensity is positively associated with recall of positive images in CONT subjects, but negatively associated with recall of positive images in aMCI subjects. Intensity is positively associated with recall of negative images in aMCI/D+ and LLD subjects. A third experiment compares these same groups on their semantic knowledge of biological and man-made objects. Only aMCI/D+ are impaired on this task, and their perofmrance is particularly impaired for biological items. Performance of aMCI and LLD groups, on the other hand, is normal. This dissertation provides compelling evidence that aMCI, aMCI/D+ and LLD individuals present distinct cognitive characteristics, namely on tests of episodic and semantic memory. The results have important theoretical and clinical implications, in that they contribute to clarifying the semiological features of each group, and corroborate the notion that each of these syndromes is cognitively distinct. In addition, these results contribute to clarifying the nosology of aMCI/D+, which paves the way for future research exploring treatment opportunities for this condition

Radiological-pathological correlation in Alzheimer's disease : systematic review of antemortem MRI findings

Background: The standard method of ascertaining Alzheimer’s disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these aetiologies and provide a diagnosis in vivo. Objective: We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD. Methods: We explored PubMed in June-July 2015 using “Alzheimer’s disease” and combinations of radiological and pathological terms. After exclusion following screening and full-text assessment of the 552 extracted manuscripts, three others were added from their reference list. In fine, we report results based on 27 articles. Results: Independently of normal age-related brain atrophy, AD pathology is associated with whole-brain and hippocampal atrophy and ventricular expansion as observed on T1-weighted images. Moreover, cerebral amyloid angiopathy and cortical microinfarcts are also related to brain volume loss in AD. Hippocampal sclerosis and TDP-43 are respectively associated with hippocampal and medial temporal lobe atrophy. Brain volume loss correlates more strongly with tangles than with any other pathological finding. White matter hyperintensities observed on proton density, T2-weighted and FLAIR images are strongly related to vascular pathologies, but are also associated with other histological changes such as gliosis or demyelination. Discussion: Cerebral atrophy and white matter changes in the living brain reflect underlying neuropathology and may be detectable using antemortem MRI. In vivo MRI may therefore be an avenue for AD pathological staging

Risk of neurodegenerative disease or dementia in adults with attention-deficit/hyperactivity disorder: a systematic review

Purpose of reviewSeveral psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, has been understudied in relation to dementia risk. We summarized existing literature investigating the risk of incident neurodegenerative disease or dementia associated with ADHD.Recent findingsWe searched five databases for cohort, case–control, and clinical trial studies investigating associations between ADHD and neurodegenerative diseases/dementia in May 2023. Study characteristics were extracted by two independent raters, and risk of bias was assessed using the Newcastle Ottawa Scale. Search terms yielded 2,137 articles, and seven studies (five cohort and two case–control studies) ultimately met inclusion criteria. Studies examined the following types of neurodegeneration: all-cause dementia, Alzheimer’s disease, Parkinson’s and Lewy body diseases, vascular dementia, and mild cognitive impairment. Heterogeneity in study methodology, particularly covariates used in analyses and types of ratios for risk reported, prevented a meta-analysis and data were therefore summarized as a narrative synthesis. The majority of studies (4/7) demonstrated an overall low risk of bias.SummaryThe current literature on risk of developing a neurodegenerative disease in ADHD is limited. Although the studies identified present evidence for a link between ADHD and subsequent development of dementia, the magnitude of the direct effect of ADHD on neurodegeneration is yet to be determined and better empirically designed studies are first needed. Furthermore, the mechanism of how or why ADHD is associated with an increased risk of developing a neurocognitive disorder is still unclear and should be explored in future studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348976, the PROSPERO number is CRD42022348976

Normative data for the dementia rating scale in the french-Quebec population

The Dementia Rating Scale-2 is used to measure cognitive status of adults with cognitive impairment, especially of the degenerative type, by assessing five cognitive functions, namely attention, initiation/perseveration, construction, conceptualization, and memory. The present study aimed to establish normative data for this test in the elderly French-Quebec population. A total of 432 French-speaking elders from the province of Quebec (Canada), aged 50 to 85 years, were administered the Dementia Rating Scale-2. Age and education were found to be associated with the total score on the test, while gender was not. Percentile ranks were then calculated for age- and education-stratified groups. Previous studies have shown that cultural background can affect performance on the DRS and the development of culture-specific norms for French-speaking Quebecers could be very useful to clinicians and researchers working with this population

The Grizzly, September 26, 1995

Ursinus Improves in National Rankings • Racism in Everywhere • The Dawn of a New S.T.A.R. • Royersford Teachers Strike • Restaurant Night is Back! • Stories from Abroad • Help, I\u27m an E-mail Addict! • Political Parties, Presidents, and Colin Powell • Writing Off Old Men\u27s? • Way to go, Collegeville! • Letters to the Editor • Spirit of Life Ensemble to Perform • Tobin Display at Berman • Are Wismer\u27s Grades Slipping? • Hillel Trip a Success • Celebrating Hispanic Heritage • What\u27s Going on at Ursinus College? • U.S.G.A. Minutes • C.A.B. Minutes • Conserve, Conserve, Conserve! What You Can do to Save Energy and the Earth • Soccer Team Splits • Field Hockey Team Wins Fourth Straight • Runners Compete • Football Team Not Offensive in Loss • Volleyball Team Nets Third Winhttps://digitalcommons.ursinus.edu/grizzlynews/1363/thumbnail.jp

White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer\u27s disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

Memory for emotional images differs according to the presence of depressive symptoms in individuals at risk for dementia

Background: Studies of amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) have examined the similarities and differences between these syndromes, but few have investigated how the cognitive profile of comorbid aMCI and subclinical depressive symptoms (aMCI/D+) may compare to that of aMCI or LLD. Memory biases for certain types of emotional information may distinguish these groups. Methods: Thirty-five aMCI, 23 aMCI/D+, 13 LLD, and 17 elderly controls (CONT) rated the valence (positive, negative or neutral) of 30 pictures from the International Affective Picture System. Mean percent positive, negative and neutral images recalled was compared within groups immediately and 30 minutes later. Results: Overall memory performance was comparable in aMCI and aMCI/D+, and both recalled fewer items than CONT and LLD. Group differences emerged when valence ratings were considered: at immediate and delayed recall, positive and negative pictures were generally better-remembered than neutral pictures by CONT, aMCI, and LLD, but valence was not associated with recall in aMCI/D+. Follow-up analyses suggested that the perceived intensity of stimuli may explain the emotional enhancement effect in CONT, aMCI, and LLD. Conclusions: Results support previous research suggesting that the neuropsychological profile of aMCI/D+ is different from that of aMCI and LLD. Although depressed and non-depressed individuals with aMCI recall comparable quantities of information, the quality of the recalled information differs significantly. On theoretical grounds, this suggests the existence of distinct neurobiological or neurofunctional manifestations in both groups. Practically, these differences may guide the development of personalized emotion-focused encoding strategies in cognitive training programs

Adult ADHD: Risk Factor for Dementia or Phenotypic Mimic?

Attention-deficit hyperactivity disorder (ADHD) has historically been considered a disorder of childhood and adolescence. However, it is now recognized that ADHD symptoms persist into adulthood in up to 60% of individuals. Some of the cognitive symptoms that characterize ADHD (inability to provide sustained attention or mental effort, difficulty organizing or multi-tasking, forgetfulness) may closely resemble symptoms of prodromal dementia, also often referred to as mild cognitive impairment (MCI), particularly in patients over age 50. In addition to the overlap in cognitive symptoms, adults with ADHD and those with MCI may also share a number of behavioral and psychiatric symptoms, including sleep disturbances, depression, and anxiety. As a result, both syndromes may be difficult to distinguish clinically in older patients, particularly those who present to memory clinics with subjective cognitive complaints and fear the onset of a neurodegenerative process: is it ADHD, MCI, or both? Currently, it is unclear whether ADHD is associated with incipient dementia or is being misdiagnosed as MCI due to symptom overlap, as there exist data supporting either possibility. Here, we aim to elucidate this issue by outlining three hypothetical ways in which ADHD and MCI might relate to each other, providing an overview of the evidence relevant to each hypothesis, and delineating areas for future research. This is a question of considerable importance, with implications for improved diagnostic specificity of early dementia, improved accuracy of disease prevalence estimates, and better identification of individuals for targeted treatment