Memory Scores Research Articles

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

Personality traits related to cognitive functioning in patients with functional neurological disorder

ABSTRACT Cognitive symptoms are prevalent in patients with functional neurological disorder (FND). Several studies have suggested that personality traits such as neuroticism may play a pivotal role in the development of FND. FND has also been associated with alexithymia: patients with FND report difficulties in identifying, analyzing, and verbalizing emotions. Whether or not alexithymia and other personality traits are associated with cognitive symptomatology in patients with FND is unknown. In the current study, we explored whether the Big Five personality model factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and alexithymia were associated with cognitive functioning in FND. Twenty-three patients with FND were assessed using a neuropsychological assessment and questionnaire assessment to explore personality traits (Neuroticism-Extraversion-Openness Five-Factor Inventory) and alexithymia (Bermond-Vorst Alexithymia Questionnaire). The results indicated that high conscientiousness was associated with lower planning scores (ρ = −0.52, p = .012) and high scores on alexithymia were associated with lower scores on verbal memory scores (ρ = −0.46, p = .032) and lower sustained attention scores (ρ = −0.45, p = .046). The results did not remain significant after controlling for multiple testing. The preliminary results of our study suggest that personality and cognitive symptomatology in patients with FND are topics that should be further explored in future studies, as cognitive symptomology can affect treatment results.

When Failing One Performance Validity Test Matters

There appears to be a lack of consensus regarding how best to interpret cognitive test findings when there is a failure on only one Performance Validity Test (PVT). The current study examined the impact of failing one freestanding, forced-choice, memory-based (Fr-FC-MB) PVT across two memory measures in a large sample of veterans (N = 1,353). The impact of failing zero, one, or two Fr-FC-MB PVTs (Test of Memory Malingering Trial 1 or the Medical Symptom Validity Test) on subsequent memory measures was examined (California Verbal Learning Test-II [CVLT-II], Brief Visuospatial Memory Test-R [BVMT-R]). Compared to those failing zero PVTs, those failing one PVT showed significant declines across all memory indices with large average effect sizes (BVMT-R, d = −0.9, CVLT-II, d = −1.0). Those failing one PVT had memory scores more similar to those failing two PVTs. There is a need for greater nuance and flexibility when determining invalid test performance. The current findings, along with a brief review of the literature, find that failing even one Fr-FC-MB PVT dramatically (negatively) impacts memory performance. Results suggest that including individuals failing one Fr-FC-MB PVT into a credible group should be more closely scrutinized.

The Effect of Physical Activity Level on Executive Functions in Obese Cases

The Effect of Physical Activity Level on Executive Functions in Obese Cases Abstract Objective: The aim of this study was to compare the executive functions (inhibitory control, cognitive flexibility and working memory) of obese subjects with different levels of physical activity. Material and Method: The study included 31 obese subjects. The patients were divided into 2 groups as high physical activity (HAOG, n=14) and minimal physical activity (MAOG, n=17) according to International Physical Activity Questionnaire-Short Form (IPAQ-SF). After demographic data of the subjects were recorded, body fat ratio was assessed by bioelectrical impedance analysis. Inhibitory control, cognitive flexibility and working memory were evaluated with Stroop Test Çapa Form, Trail Making Test A-B and 2-back test, respectively. Results: Body mass index, age, waist circumference, hip circumference and waist/hip ratio were similar between the groups, whereas percentage of fat mass was lower in HAOG (p=0.016) and percentage of muscle mass was higher in HAOG (p=0.009). Inhibitory control, cognitive flexibility and working memory scores were similar in the groups in our study (p&gt;0.005). Conclusion: According to the results of our study, although executive functions were similar in obese subjects with different physical activity levels, further studies comparing obese groups with different physical activity levels are needed due to the limitations of publications in this field. Keywords: Obesity, executive function, physical activity.

Association of obstructive sleep apnea and sleep quality with cognitive function: a study of middle-aged and elderly persons in India.

Symptoms of obstructive sleep apnea (OSA) and poor sleep quality affect around one in ten people in India. We aimed to determine if OSA symptoms and poor sleep quality are independently associated with cognition in middle-aged and elderly urban Indian populations. We studied the cross-sectional association between OSA symptoms (by Berlin Questionnaire), poor sleep quality (by Pittsburgh Sleep Quality Index), and cognitive function in adults ≥ 50years. Using a standard neuropsychological battery for cognitive function, a G-factor was derived as the first rotated principal component assessing domains of information processing, memory, and executive function. The associations of exposures with cognitive measures were modeled using linear regression, adjusted for metabolic risk factors, lifestyle factors, and psychosocial problems, followed by stratified analysis by decadal age group. A total of 7505 adults were enrolled.Excluding those with MMSE < 26 (n 710), of 6795 individuals (49.2% women), mean (SD) age 64.2 (9.0) years, 38.3% had high risk of OSA symptoms, and 15.9% had poor sleep quality. OSA symptoms were negatively associated with cognitive domains of information processing (adjusted beta coefficient of z-score - 0.02, p-value 0.006), memory (- 0.03, 0.014), and G-factor (- 0.11, 0.014) in full-model. Stratified analysis by age group showed significant adverse effects of OSA symptoms on cognition for middle-aged people (50-60years) (- 0.26, 0.001), but not in later age groups. Poor sleep quality was also associated with lower cognitive scores for G-factor (- 0.48, < 0.001), memory (- 0.08, 0.005), and executive domains (- 0.12, < 0.001), but not with information domain. The findings suggest that both symptoms of OSA and poor sleep quality have a direct adverse impact on cognition in an Indian setting. A modest effect of age on the relationship of OSA and cognition was also observed.

The association between cardiovascular health and cognition in adults with Down syndrome

IntroductionEvidence in the general population suggests that predictors of cardiovascular health such as moderate to vigorous physical activity (MVPA), cardiorespiratory fitness, and systolic blood pressure are associated with cognitive function. Studies supporting these associations in adults with Down syndrome (DS) are limited. The purpose of this study was to examine the associations between systolic blood pressure, cardiorespiratory fitness, and MVPA on cognition in adults with DS.MethodsThis is a cross-sectional analysis using baseline data from a trial in adults with DS. Participants attended a laboratory visit where resting blood pressure, cardiorespiratory fitness (VO2 Peak), and cognitive function (CANTAB® DS Battery) were obtained. The cognitive battery included tests measuring multitasking, episodic memory, and reaction time. Physical activity (accelerometer) was collected over the week following the laboratory visit. Pearson correlations and linear regressions were used to measure the impact of systolic blood pressure, cardiorespiratory fitness, and MVPA on cognitive outcomes.ResultsComplete data was available for 72 adults with DS (26.8 ± 9.3 years of age, 57% female). At baseline, VO2 Peak (21.1 ± 4.2 ml/kg/min) and MVPA were low (14.4 ± 14.4 min/day), and systolic blood pressure was 118.3 ± 13.3 mmHg. VO2 Peak was correlated with simple movement time (rho = − 0.28, p = 0.03) but was not significant using a linear regression controlling for age and sex. Systolic blood pressure was significantly associated with episodic memory (first attempt memory score: β = − 0.11, p = 0.002; total errors: β = 0.58, p = 0.001) and reaction time (five-choice movement time: β = 4.11, p = 0.03; simple movement time: β = 6.14, p = 0.005) using age- and sex-adjusted linear regressions. No associations were observed between MVPA and multitasking, episodic memory, or reaction time.ConclusionPredictors of cardiovascular health, including cardiorespiratory fitness and systolic blood pressure, were associated with some aspects of cognition in adults with DS. While future research should examine the role of improved cardiovascular health on delaying decreases in cognitive function and dementia in adults with DS, we recommend that health care providers convey the importance of exercise and cardiovascular health to their patients with DS.Trial registrationNCT04048759, registered on August 7, 2019.

NODDI Identifies Cognitive Associations with In Vivo Microstructural Changes in Remote Cortical Regions and Thalamocortical Pathways in Thalamic Stroke.

The roles of cerebral structures distal to isolated thalamic infarcts in cognitive deficits remain unclear. We aimed to identify the in vivo microstructural characteristics of remote gray matter (GM) and thalamic pathways and elucidate their roles across cognitive domains. Patients with isolated ischemic thalamic stroke and healthy controls underwent neuropsychological assessment and magnetic resonance imaging. Neurite orientation dispersion and density imaging (NODDI) was modeled to derive the intracellular volume fraction (VFic) and orientation dispersion index. Fiber density (FD) was determined by constrained spherical deconvolution, and tensor-derived fractional anisotropy (FA) was calculated. Voxel-wise GM analysis and thalamic pathway tractography were performed. Twenty-six patients and 26 healthy controls were included. Patients exhibited reduced VFic in remote GM regions, including ipsilesional insular and temporal subregions. The microstructural metrics VFic, FD, and FA within ipsilesional thalamic pathways decreased (false discovery rate [FDR]-p < 0.05). Noteworthy associations emerged as VFic within insular cortices (ρ = -0.791 to -0.630; FDR-p < 0.05) and FD in tracts connecting the thalamus and insula (ρ = 0.830 to 0.971; FDR-p < 0.001) were closely associated with executive function. The VFic in Brodmann area 52 (ρ = -0.839; FDR-p = 0.005) and FA within its thalamic pathway (ρ = -0.799; FDR-p = 0.003) correlated with total auditory memory scores. In conclusion, NODDI revealed neurite loss in remote normal-appearing GM regions and ipsilesional thalamic pathways in thalamic stroke. Reduced cortical dendritic density and axonal density of thalamocortical tracts in specific subregions were associated with improved cognitive functions. Subacute microstructural alterations beyond focal thalamic infarcts might reflect beneficial remodeling indicating post-stroke plasticity.

Association of Chronic Anti‐GERD Medication Usage and Cognitive Decline in a Racially Diverse Elderly Population

AbstractBackgroundIt is understood that early medical intervention of various diseases, like cardiovascular or gastroenterological, is a potential way to mitigate the progression of cognitive decline and dementia. However, some medications’ mechanisms of action (MOA), may alter the metabolism of foods and absorption of nutrients and inhibit neurotransmitters. The long‐term influence of chronic medication use on cognition in a racially‐diverse elderly population is unknown. As such, we aim to investigate how chronic use of specific Anti‐GERD medications (e.g., proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA’s), may be associated with global cognitive decline and cognitive functional domainsMethodUtilizing data collected from a long‐running, community‐based study, the Chicago Health and Aging project (CHAP) which started in 1993, we examined the association of anti‐GERD medication use and cognition in n = 7742, 1268 (16%) PPI users and 939 (12%) H2RA users, aged ≥65 years. This study sample consists of 63% African American (AA) participants and 60% female participants. Recruitment and data collection occurred in triennial cycles. Medication use was assessed through direct observation while neuro‐cognition was evaluated using a battery of 4‐standardized cognitive tests. Using linear mixed effects change‐point models, adjusted for age, sex, education and race, we investigated whether chronic anti‐GERD medication usage is associated with cognitive declineResultOf anti‐GERD medication users, after starting the medication, chronic use of PPI’s was associated with a faster rate of global cognitive decline β = ‐0.028 (p≤0.000), memory score β = ‐0.023 (p≤0.000) and speed score β = ‐0.012 (p≤0.034). H2RA’s were not associated with global cognition or memory score but were suggestive for speed score β = ‐0.011 (p≤0.057). In models stratified by race and separately, sex, after starting, chronic PPI use was associated with faster global cognitive decline in AA β = ‐0.030 (p≤0.000), White β = ‐0.026 (p≤0.001) and female β = ‐0.037 (p≤0.000) but not male individuals. H2RA’s were only associated with faster global cognitive decline in White individuals β = ‐0.025 (p≤0.039)ConclusionChronic use of PPI’s and H2RA’s may be associated with faster rates of global cognitive decline and memory &amp; speed scores in an elderly population. The associative results presented, demonstrate the need for further investigation into how medication usage potentially impacts cognition

Performance of the CANTAB ‐ Paired Associates Learning task in an unsupervised online setting: Results from the Brain Health Registry

AbstractBackgroundThe aim of this study was to evaluate the feasibility and usability of collecting data from an unsupervised online version of the Paired Associates Learning (PAL) task from the Cambridge Neuropsychological Test Automated Battery (CANTAB™) in adults enrolled in the Brain Health Registry (BHR).MethodBHR is an online cognitive aging registry for referral and longitudinal unsupervised assessment. The PAL assesses visual associative learning and memory and was administered in BHR between 03/2021‐07/2022. PAL variables included in this analysis were ‘Memory Score’ (patterns correctly identified at first attempt for each difficulty level) and ‘Total Errors’, adjusted for level reached. We analyzed PAL task completion rate and characteristics of PAL completers and used linear regressions to assess whether cross‐sectional PAL Memory Score and PAL Total Errors were associated with participant data (age, gender, education, self‐ and study partner‐reported cognitive complaints (Everyday Cognition scale (ECog)), self‐reported memory concern, and self‐reported depressive symptom severity (PHQ‐9), self‐report of Mild Cognitive Impairment (MCI)).ResultAs of July 2022, 14,520 participants aged 18+ years have completed PAL at least once. Participants were on average 66.3 years old (SD = 11.3), 72.4% female gender, 92.8% self‐identified as White, and had a mean of 16.6 years of education (SD = 2.27). BHR received 374 requests for study support regarding PAL, of which 36% (135) were related to device compatibility. Mean PAL scores were similar to those of previous, supervised studies (Figure 1). Worse PAL performance was significantly associated with being older, female gender, having less education, more self‐ and study partner‐reported ECog, self‐reported memory concern, more depressive symptoms, and self‐report of MCI (Table 1).ConclusionOur findings provide evidence for the feasibility of collecting PAL data in an unsupervised online setting and construct validity of cross‐sectional BHR PAL. In terms of usability, there was a minimal need for support. Future studies will investigate the predictive value of BHR PAL in identifying adults with self‐reported MCI, longitudinal BHR PAL performance and associations with in‐clinic assessments and Alzheimer’s disease biomarkers. Our sample lacked diversity. Therefore, a future direction is to increase accessibility of PAL to ethnoculturally and socioeconomically diverse communities.

Amyloid and Tau Predominance Subtyping Identifies CI Patients With Different Clinical Phenotypes

AbstractBackgroundThe ATN classification system assumes a sequential model of disease progression. However, there are groups of individuals in the same ATN category that exhibit a predominance of abnormality (higher burden) of one of the biomarkers, creating heterogeneous ATN groups regarding pathological predominance. Thus, we tested the hypothesis that individuals clustered by ATN biomarker abnormality predominance may offer an alternative to groups defined using biomarkers cut‐offs.MethodWe assessed 103 cognitively impaired individuals(CDR&gt; = 0.5) from the TRIAD cohort with available measures of plasma phosphorylated tau‐181, brain MRI, amyloid PET, and tau PET. We used the K‐means algorithm to stratify participants into three clusters. We compared the clusters on composite measures of memory, executive functioning, language, and visuospatial processing. To examine the utility of the discovered clusters, we compared them to traditional ATN categories in the prediction of neuropsychological measures. We did so by creating three categories: patients positive on all three ATN biomarkers, patients positive on two of the three biomarkers, and patients positive on either one or none. Additionally, we created an inflammation, amyloid and tau deposition probabilistic map anchored on young controls(n = 51, mean age = 23.74).ResultsWe uncovered 3 clusters: an amyloid predominant (AP) cluster, a tau/phosphor‐tau predominant cluster (TP), and a cluster showing no predominance with low levels on all biomarkers (CN)(figure 1). Notably, levels of neurodegeneration and inflammation were similar between the AP and TP clusters. The AP cluster significantly differed from the CN cluster in memory only. Participants in the TP cluster had significantly lower scores in memory, executive functioning, language, and visuospatial processing than the other two clusters. In comparison, using threshold‐based ATN groups showed milder differences in memory and executive functioning, and no differences in language and visuospatial processing(figure 2). Furthermore, cluster membership moderated the relationship between various biomarkers, to the point of reversing the direction of correlation(figure 3).ConclusionOur results highlight the biological heterogeneity present within the Alzheimer’s disease continuum and that the pathological predominance of amyloid and tau is associated with different disease phenotypes. Approaching dementia patients with an eye on the predominance of pathology rather than cutoffs for abnormality may provide a better understanding of AD pathological subtypes.

Amyloid and Tau Predominance Subtyping Identifies CI Patients With Different Clinical Phenotypes

AbstractBackgroundThe ATN classification system assumes a sequential model of disease progression. However, there are groups of individuals in the same ATN category that exhibit a predominance of abnormality (higher burden) of one of the biomarkers, creating heterogeneous ATN groups regarding pathological predominance. Thus, we tested the hypothesis that individuals clustered by ATN biomarker abnormality predominance may offer an alternative to groups defined using biomarkers cut‐offs.MethodWe assessed 103 cognitively impaired individuals(CDR&gt; = 0.5) from the TRIAD cohort with available measures of plasma phosphorylated tau‐181, brain MRI, amyloid PET, and tau PET. We used the K‐means algorithm to stratify participants into three clusters. We compared the clusters on composite measures of memory, executive functioning, language, and visuospatial processing. To examine the utility of the discovered clusters, we compared them to traditional ATN categories in the prediction of neuropsychological measures. We did so by creating three categories: patients positive on all three ATN biomarkers, patients positive on two of the three biomarkers, and patients positive on either one or none. Additionally, we created an inflammation, amyloid and tau deposition probabilistic map anchored on young controls(n = 51, mean age = 23.74).ResultWe uncovered 3 clusters: an amyloid predominant (AP) cluster, a tau/phosphor‐tau predominant cluster (TP), and a cluster showing no predominance with low levels on all biomarkers (CN)(figure 1). Notably, levels of neurodegeneration and inflammation were similar between the AP and TP clusters. The AP cluster significantly differed from the CN cluster in memory only. Participants in the TP cluster had significantly lower scores in memory, executive functioning, language, and visuospatial processing than the other two clusters. In comparison, using threshold‐based ATN groups showed milder differences in memory and executive functioning, and no differences in language and visuospatial processing(figure 2). Furthermore, cluster membership moderated the relationship between various biomarkers, to the point of reversing the direction of correlation(figure 3).ConclusionOur results highlight the biological heterogeneity present within the Alzheimer’s disease continuum and that the pathological predominance of amyloid and tau is associated with different disease phenotypes. Approaching dementia patients with an eye on the predominance of pathology rather than cutoffs for abnormality may provide a better understanding of AD pathological subtypes.

Executive function performance depends on hypertension in individuals with sub‐threshold total Hachinski score

AbstractBackgroundThe Hachinski Ischemia Scale (HIS) differentiates AD and vascular dementia and is used to include individuals with minimal vascular risk factors in ADNI i.e., HIS ≤ 4. HIS score includes history of hypertension (HMHYPERT), a known risk for mild cognitive impairment (MCI) and vascular dementia. Cerebrovascular disease affects performance on tasks involving executive function, such as, planning and processing speed more than memory. Here, we determined if HMHYPERT scores influences executive functioning in all ADNI3 participants with normal cognition (CN) and MCI even with minimal vascular risks.MethodWe included a total of 272 participants (102 MCI, age = 74± 8 [42F, 50 HMHYPERT&gt;0], MoCA = 23 ±3 and 170 CN, age = 73 ±6, [109F, 62 HMHYPERT&gt;0], MoCA = 26 ±3), who underwent HIS, Trails Making Test B, Clock Drawing and Copy scores for executive function, and The Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LOGMEM) scores for memory performance within 12 months. We converted both memory tests into z‐scores and created a composite memory score. Similarly, we created a composite executive function score. To determine if HMHYPERT was associated particularly with executive function, we ran the linear regression analyses twice for the two composite cognitive scores. The following model was used: Composite score ∼ Normalized Age + Sex + Cognitive status * HMHYPERT.Result Executive function: Fig. 1 A shows scores for Trails B, Clock Draw and Clock Copy. The regression analysis showed that executive function was associated with only sex and HYMHYPERT (p&lt;0.05).Memory function Fig. 1 B shows scores for Logical Memory and RAVLT tests in CN and MCI. As expected, MCI groups demonstrate the lowest averages compared to CN groups. As expected, regression analysis showed that memory performance was strongly determined by diagnostic status (p&lt;0.001). Age was significantly associated with memory performance (p&lt;0.05). HMHYPERT was only marginally significantly associated with memory performance (p = 0.08).ConclusionUsing HMHYPERT score as a measure of vascular risk, we observed notable differences in executive function. Although HIS scores ≤ 4 minimize vascular pathology in ADNI3, cognitive performance is still associated with these scores.

Association between G‐Protein Coupled Receptor 55 (GPR55) Single Nucleotide Polymorphisms and Alzheimer’s Disease

AbstractBackgroundG‐protein‐coupled receptor 55 (GPR55) is a lysophosphatidylinositol and novel cannabinoid receptor. GPR55 signalling and single nucleotide polymorphisms (SNPs) have been implicated as a potential therapeutic target for neurodegenerative diseases such as Alzheimer’s Disease (AD); however, foundational knowledge on the role of GPR55 in AD progression remains lacking. We hypothesised GPR55 SNP minor allele carriers would have greater brain atrophy, cognitive decline, and AD‐related biomarker changes.MethodThis retrospective, longitudinal, observational study used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We selected participants with clinically normal cognition, mild cognitive impairment (MCI) or mild AD from ADNI2 and ADNIGO phases as a discovery sample. Exploratory screening of GPR55 SNPs identified rs2969126G/C associated with brain volume. Cerebrospinal fluid amyloid beta‐42 (CSF‐Aβ42), total and phosphorylated‐tau (t/p‐tau) were considered. Mini‐Mental State Exam and the Logical Memory Delayed Recall Test were also selected to evaluate overall cognitive status, executive function, and memory. ANCOVA models evaluated baseline differences between SNP carriers and major allele homozygotes (dominant model), controlling for sex, age, baseline cognitive status and APOE e4 across AD biomarkers, brain volumetrics and cognitive measures. Longitudinal associations were assessed as interactions between SNP and visit (baseline, 12 and 24 months) in mixed models.ResultIn ADNI2/GO (n = 755), minor allele carriers represented 15% of the sample. Significantly greater decline in CSF‐Aβ42 levels was observed in Aβ42‐positive clinically normal minor allele carriers (F(1,45.2) = 6.35, p = 0.015). Carriers with MCI had significantly higher t‐tau (F(1,126) = 4.303, p = 0.04) and p‐tau concentrations (F(1,129) = 6.98, p = 0.009) longitudinally. Significantly smaller hippocampal volumes over time were seen in minor allele carriers in the whole group (F(1,444) = 5.74, p = 0.017), with a trend in the AD/MCI subgroup (F(1,325) = 3.364, p = 0.06). Clinically normal minor allele carriers had significantly poorer baseline logical memory scores (F(1,285) = 6.92, p = 0.009). These results did not replicate in the ADNI3 cohort.ConclusionCarriers of the GPR55 SNP rs2969126G/C minor allele had greater Aβ42 and tau biomarker abnormalities, smaller brain volumes and poorer memory scores over time in different stages of AD. This preliminary study prompts replication studies in different stages of AD progression to implicate GPR55 as a potential therapeutic target for AD.

Changes in cognitive functioning by a multifactorial intervention to prevent dementia‐The Japan‐Multimodal Intervention Trial for Prevention of Dementia PRIME Tamba‐

AbstractBackgroundMany efforts for early detection and prevention of cognitive decline have been reported. In this study, we examined the changes in possible Nou‐KNOW (Cognigram by Cogstate; Japanese version Cognigram) after an 18‐month multifactorial intervention to prevent dementia in cognitively normal elderly subjects living in areas at risk for dementia.MethodThe Japan‐Multimodal Intervention Trial for Prevention of Dementia PRIME Tamba (J‐MINT), a randomized controlled trial to prevent cognitive decline in cognitively normal older people living in areas at risk of dementia, was conducted. PRIME Tamba), a randomized controlled trial to prevent cognitive decline. 203 participants (male: 57 participants, mean age: 73.86±4.84, mean MMSE score: 28.65±1.36) were randomly assigned to the intervention group (101 participants) or the control group (102 participants). The intervention group received 90 minutes of group‐based physical exercise once a week, cognitive training, nutritional counseling, and vascular risk factor management for 18 months (78 sessions in total). Reaction speed, attention, visual learning, and attentional scores were measured twice (Baseline and 18 months after intervention) by the Nou‐KNOW. Statistical analyses were conducted using a general linear mixed‐effects model with a significance level of less than 5%.ResultThere was a statistically significant difference in the Reaction time score (intervention group vs. control group; 101.62 ± 7.07 vs. 98.63 ± 9.75, p&lt;0.01) and Attention score (100.19 ± 7.19 vs. 98.16 ± 7.56, p = 0.02) in the Cognigram at the 18‐month measurement in the intervention group. On the other hand, no statistically significant differences were found in the Visual memory score (100.26±13.26 vs. 98.63±13.71, p = 0.89) and Working memory score (98.99 ± 8.13 vs. 96.71 ± 7.39, p = 0.29).ConclusionAn 18‐month multifactorial intervention to prevent dementia in cognitively normal older adults living in areas at risk for dementia was suggested to improve reaction time and attention.

The effect of APOEƐ4 on neurocognitive decline is accentuated by female sex and menopause: Identification of mitigating interventions

AbstractBackgroundTwo thirds of those living with AD are female. Age‐standardised AD prevalence is consistently higher at all ages over 70 years in women versus men. The aetiology of the accelerated neurophysiological decline in females is poorly understood. Here we investigate the independent and interactive impact of APOE4 carrier status and menopause.MethodTargeted replacement (APOE3‐TR and APOE4‐TR) rodent models and human cohort studies (European Prevention of Alzheimer’s Dementia (EPAD) and UK Biobank (UKB)) were used to investigate the impact of APOE4, menopause and hormone replacement therapy (HRT) on cognition, brain volumes (assessed by MRI), omega‐3 fatty acid status and synaptic function. In rodents, menopause is elicited by the administration of 4‐vinylcyclohexene diepoxide (VCD), which induces a human‐like “perimenopausal” phenotype, whilst maintaining ovarian tissue integrity.ResultsIn EPAD, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery, HRT use in APOE4 only was associated with higher overall cognition and (delayed) memory scores and larger entorhinal and amygdala volumes in APOE4 only. Earlier HRT introduction was associated with larger hippocampal volumes. In UKB, HRT use was associated with improved memory in APOE4/E4. In mice, VCD administration reduced recognition memory, brain docosahexaenoic acid (DHA, omega‐3 fatty acid) levels, and altered synaptic plasticity biomarkers in APOE4‐TR animals, which was mitigated by DHA supplementation (1).ConclusionAn increased penetrance of the APOE4 genotype during the menopausal transition is likely to contribute to the higher incident AD in females, and in APOE4 females versus non‐carriers. HRT and DHA intervention during the menopausal transition, as a critical window of opportunity, may represent effective strategies to support cognitive health into older age in this ‘at‐risk’ (APOE4 female) group, which typically represent 12% of Caucasian populations compared and 33‐50% of AD.1. Pontifex MG et al., FASEB J. 2021 May;35(5):e21583

Bidirectional associations between quality of life and cognitive function over 17 years: Evidence from the English Longitudinal Study of Ageing (ELSA)

AbstractBackgroundDepression and anxiety are well recognised as risk factors for dementia and poorer cognitive outcomes. However, considerably less is known about the relationship between quality of life and cognitive function over time. Quality of life is not simply the absence of mental health problems, but instead is a related but distinct construct. In particular, it is unclear whether poorer quality of life precedes cognitive decline, or vice versa or whether there is a bidirectional relationship. This is of import because understanding directionality allows us to start to plan interventions around dementia risk reduction. The aim of this study was to test bidirectionality between quality of life and memory in a large, nationally representative sample of people aged 50+ without cognitive impairment.MethodData were used from the English Longitudinal Study of Ageing (ELSA), a longitudinal cohort comprising 12,099 people over the age of 50 and their partners. Repeated measures of quality of life and memory (immediate and delayed) were available nine times over a 17‐year period. Cross‐lagged models were fitted to test for bidirectionality between quality of life and memory function.ResultThe fully adjusted model revealed that higher quality of life was significantly associated with higher subsequent immediate memory scores at all time‐points, and with higher subsequent delayed memory scores at all except the final time‐point. There was no consistent evidence that memory was significantly associated with subsequent quality of life.ConclusionThese results extend previous research by providing evidence for the temporal association between quality of life and memory in a population‐based sample of people aged 50+. Specifically, results suggest that quality of life is consistently associated with later memory function over nearly two decades, though the study did not provide evidence that the association operates in the opposite direction. The lack of consistent evidence for a relationship between cognitive function and subsequent quality of life may be due to the exclusion of people with cognitive impairment and adjustment for depressive symptoms. Better quality of life may act as a protective factor in retaining memory function from middle to later adulthood.

Language, Subjective Cognitive Decline and Help Seeking in Latinx

AbstractBackgroundSubjective cognitive decline (SCD) is a marker of Alzheimer’s disease and related dementia (ADRD) risk, as well as a reason why older adults seek medical help. However, whether the concept of SCD has utility in Latinx populations has been questioned because SCD’s inconsistent associations with cognition in this population. Measurement factors, such as how we ask about SCD (e.g., age‐anchoring) and person factors (e.g., preferred language) may influence the reported level of measured SCD and/or its association with cognition and help‐seeking.MethodsParticipants included 699 (50 years and older) Latinx individuals enrolled in the Offspring study of Racial and Ethnic Disparities in Alzheimer’s Disease. Participants completed two independent SCD measures that queried if memory had become worse (general SCD) and if it had become worse compared to others their age (age‐anchored SCD). Memory was assessed via the Selective Reminding Test (SRT) total and delayed raw scores. Help‐seeking was assessed by one item that asked if individuals had talked to a nurse/doctor about their cognitive concerns. In a series of linear and logistic regressions, we evaluated the cross‐sectional relationship between 1) SCD (general and age‐anchored) and memory performance and 2) SCD and help‐seeking. Models were stratified by preferred language (English‐speakers/Spanish‐speakers) and adjusted for age, sex, education, and medical burden.ResultsSpanish‐speaking Latinx participants were on average older, had less educational attainment, had greater medical burden, and reported more general SCD, but not age‐anchored SCD, than English‐speaking Latinx participants. Memory scores did not differ across language groups. General SCD was associated with help‐seeking in Spanish‐speakers only. Greater age‐anchored SCD was associated with lower SRT total score in English‐ (R2 = 0.158, B = ‐4.289, CI = ‐8.342,‐0.236) and Spanish‐speakers (R2 = 0.178, B = ‐5.889, CI = ‐10.875,‐0.904), as well as greater help‐seeking in both groups (English‐speaking: R2 = 0.078, B = 0.842, CI = 0.056,1.740; Spanish‐speaking: R2 = 0.277, B = 2.202,CI = 1.571,2.833).ConclusionsAcross language groups, age‐anchored SCD was consistently associated with memory performance and help‐seeking among Latinx adults. In contrast, general SCD was associated with help‐seeking only in Spanish‐speakers, and not associated with memory performance. This study is the first to demonstrate the utility of age anchoring SCD assessments within both English‐ and Spanish‐speaking Latinx individuals.

The Olfactory Stress Test does not replicate in a larger sample

AbstractBackgroundWe previously published data showing that olfactory test performance changes on the University of Pennsylvania Smell Identification Test (UPSIT) following an intranasal ‘challenge’ with the anticholinergic atropine (an ‘Olfactory Stress Test’, (OST)) were significantly correlated with measures of cognition, hippocampal volume and APOE genotype in a small (n = 56) convenience sample of elders. The results suggested that this procedure might unmask incipient Alzheimer’s disease.Here, we present data from two new studies, including an attempted replication of the above findings.MethodIn study one, the full 40 item UPSIT was administered to the left nostril to 56 individuals. Data from this study were used to determine the relationship between scores on the first 20 items (booklets 1+2) with those on the second 20 items (booklets 3+4) of the UPSIT.The second study comprised 296 elders (aged 65 or older) who underwent olfactory testing, including the OST, assessment of cognition with the Audio Recorded Cognitive Screen, APOE genotyping, and hippocampal volume (in a subsample). In this study the first 20 items of UPSIT were always administered before and the second 20 items always after intranasal atropine and regression analyses were conducted to investigate for any association of the adjusted (see below) UPSIT change score following atropine with memory or hippocampal volume.ResultIn study 1, the mean score on the first 20 items of the UPSIT was 1.53 (SD 2.07) greater than the second 20 items (t = 5.55, p&lt;.001). An appropriate adjustment factor derived from these data were used to scale the study 2 raw post atropine scores (from UPSIT booklets 3+4) into equivalent scores on booklets 1+2. These post‐atropine adjusted scores were then used in the calculation of the change in (adjusted) UPSIT following atropine.In a series of stepwise linear regression analyses, after controlling for age, gender and education, the adjusted UPSIT change score did not predict any additional variance in memory scores or hippocampal volume.ConclusionIn this larger study, we failed to replicate our earlier findings. The ’Olfactory Stress Test’ is unlikely to aid in the early detection of AD.

Blood co‐expression network analysis identifies molecular pathways involved in cognitive resilience

AbstractBackgroundTwo major risk factors of Alzheimer’s disease (AD) are advanced age and the APOE‐ε4 risk allele. However, despite having these risk factors, some individuals escape from developing AD or have slower cognitive decline. In this study we hypothesized that “resilient” individuals, defined as those who remain cognitively normal despite being &gt;80 years‐old and carrying at least one copy of the APOE‐ε4 allele, have concerted changes in their blood transcriptomes that are associated with resilience to AD.MethodWe generated blood RNA‐sequence data from 105 APOE‐ε4 carriers from the Mayo Clinic Study of Aging (MCSA) who remained cognitively normal after age 80 (resilient), or who developed mild cognitive impairment (MCI) or AD (non‐resilient). Weighted gene co‐expression network analysis (WGCNA) was performed to evaluate the association of the blood co‐expression network with primary phenotypes of resilience and memory scores. To validate our findings, we constructed a consensus co‐expression network using both MCSA and a replication cohort of blood microarray data from 91 Alzheimer’s Disease Neuroimaging Initiative (ADNI) study participants who had a similar demographic profile. We annotated the consensus modules for their enrichment of cell types, biological processes, genes within previously published genome‐wide significant (GWS) AD‐associated loci, and genes that reside in consensus modules built from seven brain regions across three different autopsy cohorts. To identify genetic variants regulating blood consensus module co‐expression, we performed module quantitative trait locus (modQTL) analysis.ResultWe found co‐expression modules significantly (q&lt;0.05) correlated with the memory phenotype, logical memory delayed recall, across both MCSA and ADNI cohorts. Some of these modules were enriched with blood cell types and biological processes, including telomere maintenance, mitochondrial functions, and immune response. We found 1 module significantly (q&lt;0.05) enriched with genes near GWS AD‐associated loci and 4 modules with genes in brain consensus modules. Lastly, we found 8 modQTLs significantly (Bonferroni‐p&lt;0.05) associated with the co‐expression of 5 different modules.ConclusionWe identified blood co‐expression modules, biological pathways and specific genetic variants associated with cognitive resilience in the presence of AD risk factors. This study provides novel insights into the potential role of peripheral blood in the development of and resilience to AD.

Exploring the association between VLOM ratio and years of education in MCI and normal aging urban cohort

AbstractBackgroundMild Cognitive Impairment (MCI) is a transition state of cognitive decline from healthy brain to dementia. It is a prodrome of Alzheimer’s disease. Verbal‐Language/Orientation‐Memory (VLOM) ratio, a simply calculated index compares its language and memory scores helps to differentiate between Alzheimer’s disease and frontotemporal dementia (Mathuranath, et al.,2000). VLOM ratio is helpful in prognosticating and planning future management of the disease. The previous studies have shown the association of scores in cognitive domains with years of education (Nieto A, et al.,2016). Therefore, the objective of the study is to explore the association of years of education with VLOM ratio in MCI participants and normal participants.MethodCross sectional analysis was done using the baseline data from the cohort study Tata Longitudinal Study of Ageing (TLSA) from urban Bengaluru, India. Clinical dementia rating scale (CDR) was used to classify participants into normal and MCI category. CDR score of 0 was considered as normal, score of 0.5 as MCI. ACE III‐R (Addenbrooke’s Cognitive Examination III‐R) a neuropsychological test was administered and verbal fluency plus language to orientation plus memory (VLOM) ratio was calculated. Further, years of education was classified into three levels and comparison of VLOM ratio was made within these levels of education groups in both MCI and normal participants. Mann Whitney U test was used to compare the VLOM ratio between MCI and normal participants. VLOM ratio and years of education among the MCI and normal participants was compared using Kruskal‐Wallis test.ResultsAmong 953 participants, 69 had MCI and 884 participants had normal cognition. Comparison of VLOM ratio between MCI and normal participants showed a significant difference, with higher VLOM ratio in MCI participants (Median (IQR)) = 0.97 (0.11) vs 0.95 (0.09); p = 0.01). There was no significant difference in VLOM ratio between years of education in both normal and MCI participants.ConclusionThe VLOM ratio found to be higher in MCI group indicating that the scores in orientation and memory domain might be lower in MCI compared to Normal participants. There was no association of VLOM ratio with years of education in normal and MCI participants.