Probable Mild Cognitive Impairment Research Articles

Estimated Pulse Wave Velocity and Cognitive Outcomes: A Post hoc Analysis of SPRINT-MIND.

Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension). This study was a post hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed Using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy. 8,563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002). EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.

Diagnosis Framework for Probable Alzheimer's Disease and Mild Cognitive Impairment Based on Multi-Dimensional Emotion Features.

Emotion and cognition are intercorrelated. Impaired emotion is common in populations with Alzheimer's disease (AD) and mild cognitive impairment (MCI), showing promises as an early detection approach. We aim to develop a novel automatic classification tool based on emotion features and machine learning. Older adults aged 60 years or over were recruited among residents in the long-term care facilities and the community. Participants included healthy control participants with normal cognition (HC, n = 26), patients with MCI (n = 23), and patients with probable AD (n = 30). Participants watched emotional film clips while multi-dimensional emotion data were collected, including mental features of Self-Assessment Manikin (SAM), physiological features of electrodermal activity (EDA), and facial expressions. Emotional features of EDA and facial expression were abstracted by using continuous decomposition analysis and EomNet, respectively. Bidirectional long short-term memory (Bi-LSTM) was used to train classification model. Hybrid fusion was used, including early feature fusion and late decision fusion. Data from 79 participants were utilized into deep machine learning analysis and hybrid fusion method. By combining multiple emotion features, the model's performance of AUC value was highest in classification between HC and probable AD (AUC = 0.92), intermediate between MCI and probable AD (AUC = 0.88), and lowest between HC and MCI (AUC = 0.82). Our method demonstrated an excellent predictive power to differentiate HC/MCI/AD by fusion of multiple emotion features. The proposed model provides a cost-effective and automated method that can assist in detecting probable AD and MCI from normal aging.

Does cognitive impairment moderate the relationship between social isolation and anxiety? A 5-year longitudinal study of a nationally representative sample of community residing older adults

BackgroundAnxiety is common in older adults and social isolation is one of the leading factors associated with their anxiety. However, what is unknown is how the relationship between social isolation and anxiety differs by cognitive status. Therefore, this study was conducted to (1) compare the level of social isolation and anxiety in older adults who developed probable dementia and mild cognitive impairment (MCI) to those who maintained normal cognitive function over 5 years; and (2) determine if cognitive impairment moderates the relationship between changes in social isolation and changes in anxiety over 5 years.MethodsA secondary data analysis was conducted using the National Social Life, Health, and Aging Project (NSHAP): Wave 2 (2010–2011) and Wave 3 (2015–2016). The participants were categorized into three groups: Participants who developed probable dementia over 5 years (4.3%), developed probable MCI (19.1%), or maintained normal cognitive function (76.6%). Weighted linear regression analyses with a group interaction were used to examine the moderating effect of cognitive impairment on the relationship between changes in social isolation and anxiety.ResultsAt the 5-year follow up, there were statistically significant differences in social isolation between the three groups (p = 0.043). Regression analyses showed that increased social isolation over time was related to increased anxiety over 5 years regardless of cognitive status after controlling for covariates (p = 0.017).ConclusionsThe relationship between social isolation and anxiety was a universal phenomenon regardless of cognitive status. Tailored interventions targeting both people with or without cognitive impairment are needed to lessen social isolation and anxiety.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction=0.81) or diastolic BP (P for interaction=0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction=0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Brief, Interoceptive Exposure Focused Treatment for Anxiety in Older Adults

AbstractBackgroundOlder adults with Mild Cognitive Impairment (MCI), Alzheimer’s disease (AD) and related dementias, and their care partners often experience high levels of anxiety. This not only diminishes their quality of life but also serves as a marker for earlier onset of ADRD symptoms for individuals experiencing MCI. Moreover, there is no well‐established treatment for those with MCI/mild AD. Anxiety sensitivity (AS) is a mechanism central to the genesis and maintenance of anxiety psychopathology that exacerbates the experience of somatic and emotional sensations, leading to increased distress. Brief, computerized, mechanism‐focused interventions have been shown to effectively reduce AS. This study sought to evaluate the acceptability and efficacy of a brief AS focused intervention in older adults with probable MCI including a repeated interoceptive exposure component and the participation of a care partner.MethodParticipants (N = 16) were recruited from the community varied in age from 65 to 81 (M = 72.44; SD = 4.83). Eligible participants enrolled in an open trial consisting of a 2‐hour intervention focused on interoceptive exposure (systematic exposure to anxiety and stress symptoms to achieve habituation). All participants completed a brief cognitive assessment, AS measures pre‐ and post‐intervention, and acceptability measures post‐intervention.ResultAverage baseline Montreal Cognitive Assessment scores were 24.25 (SD = 3.24; Range = 19‐29), which is generally indicative of MCI. Paired samples t‐tests were conducted to examine changes in total ASI‐3 scores pre‐ to post‐intervention. Despite the relatively small sample, we observed statistically significant reductions in ASI‐3 total scores with a large effect size (Δ = 4.38, Hedge’s g = .80, p&lt;.01). Additionally, the intervention was highly acceptable with 100% of participants completing the intervention and rating the quality of the intervention as good or excellent.ConclusionThis study provides encouraging evidence that brief interventions can successfully target risk mechanisms of anxiety in older adults with probable MCI. The favorable acceptability of the intervention suggests that it would be well‐received by both those with MCI and mild AD. Future research should examine this intervention in randomized‐clinical trials and study its effects longitudinally to understand how decreases in AS persist over time and relate to cognitive outcomes.

Alzheimer’s disease biomarkers of amyloid and tau influence white matter neurite alterations in dementia with Lewy bodies: a NODDI study

AbstractBackgroundCo‐morbid Alzheimer’s disease (AD) pathology in the form of amyloid‐ß plaques and tau neurofibrillary tangles are frequently observed in people with probable dementia with Lewy bodies (DLB). Neurite Orientation Dispersion and Density Imaging (NODDI) is an emerging technique to characterize white matter (WM) tissue microstructure, although NODDI alterations and associations with AD biomarkers remain undefined in DLB. The objectives of this study are to compare NODDI and DTI parameters between DLB and controls and (ii) evaluate the pattern of DTI and NODDI changes associated with amyloid and tau deposition.MethodConsecutive patients within the DLB spectrum (n = 45), including probable DLB (n = 32) and probable Mild Cognitive Impairment with Lewy bodies (MCI‐LB) (n = 13) from the Mayo Clinic ADRC underwent multi‐shell diffusion MRI, [18F]‐Flortaucipir and [11C]‐PiB PET. A comparison group of 45 age‐ and gender‐matched clinically unimpaired controls (CU) was included. Voxelwise non‐parametric permutation models were used to determine pair‐wise group differences and assess the associations of AD biomarkers with fractional anisotropy (FA), mean diffusivity (MD), tissue‐weighted neurite density index (tNDI; NDI x (1 – Free water fraction)) and orientation dispersion index (ODI), controlling for age. Complementary analyses were performed using regions‐of‐interest (ROI) obtained from the JHU atlas.ResultCompared to CU, the DLB spectrum group exhibited widespread decreases in FA and tNDI and increases in MD and ODI, with the most pronounced effects in the cingulum bundles, uncinate, inferior and superior longitudinal fasciculi (Fig. 1). Greater [18F]‐Flortaucipir uptake was also associated with lower FA and tNDI, and higher MD and ODI in the DLB spectrum compared to CU, independently of age and [11C]‐PiB uptake (Fig. 2). In contrast, no associations were found between [11C]‐PiB uptake and any of the DTI or NODDI parameters. Complementary ROI analyses corroborated these findings.ConclusionWidespread loss of WM integrity was observed on DTI and NODDI in probable DLB and prodromal DLB. These findings were associated with greater cortical tau, but not with amyloid‐ß deposition. Although alpha‐synuclein pathology underlies the loss of WM integrity in DLB, amyloid‐independent tau pathology may also be an important influence on white matter integrity within the DLB spectrum.

Alzheimer’s disease biomarkers of amyloid and tau influence white matter neurite alterations in dementia with Lewy bodies: a NODDI study

AbstractBackgroundCo‐morbid Alzheimer’s disease (AD) pathology in the form of amyloid‐β plaques and tau neurofibrillary tangles are frequently observed in people with probable dementia with Lewy bodies (DLB). Neurite Orientation Dispersion and Density Imaging (NODDI) is an emerging technique to characterize white matter (WM) tissue microstructure, although NODDI alterations and associations with AD biomarkers remain undefined in DLB. The objectives of this study are to compare NODDI and DTI parameters between DLB and controls and (ii) evaluate the pattern of DTI and NODDI changes associated with amyloid and tau deposition.MethodConsecutive patients within the DLB spectrum (n = 45), including probable DLB (n = 32) and probable Mild Cognitive Impairment with Lewy bodies (MCI‐LB) (n = 13) from the Mayo Clinic ADRC underwent multi‐shell diffusion MRI, [18F]‐Flortaucipir and [11C]‐PiB PET. A comparison group of 45 age‐ and gender‐matched clinically unimpaired controls (CU) was included. Voxelwise non‐parametric permutation models were used to determine pair‐wise group differences and assess the associations of AD biomarkers with fractional anisotropy (FA), mean diffusivity (MD), tissue‐weighted neurite density index (tNDI; NDI x (1 – Free water fraction)) and orientation dispersion index (ODI), controlling for age. Complementary analyses were performed using regions‐of‐interest (ROI) obtained from the JHU atlas.ResultCompared to CU, the DLB spectrum group exhibited widespread decreases in FA and tNDI and increases in MD and ODI, with the most pronounced effects in the cingulum bundles, uncinate, inferior and superior longitudinal fasciculi (Fig. 1). Greater [18F]‐Flortaucipir uptake was also associated with lower FA and tNDI, and higher MD and ODI in the DLB spectrum compared to CU, independently of age and [11C]‐PiB uptake (Fig. 2). In contrast, no associations were found between [11C]‐PiB uptake and any of the DTI or NODDI parameters. Complementary ROI analyses corroborated these findings.ConclusionWidespread loss of WM integrity was observed on DTI and NODDI in probable DLB and prodromal DLB. These findings were associated with greater cortical tau, but not with amyloid‐β deposition. Although alpha‐synuclein pathology underlies the loss of WM integrity in DLB, amyloid‐independent tau pathology may also be an important influence on white matter integrity within the DLB spectrum.

Plasma pTau‐217 and NfL concentrations across diagnoses in an unselected memory clinic cohort

AbstractBackgroundAlzheimer’s Disease (AD) plasma biomarkers have been proposed for amyloid positivity identification and for differentiating between diagnoses. Phosphorylated Tau‐217 (pTau‐217) has demonstrated good predictive ability for AD vs healthy controls. Neurofilament Light chain (NfL) differentiates between Frontotemporal Dementia (FTD) and other dementia. These factors have not be extensively tested in real‐world cohorts. The aim of this study was to investigate how pTau‐217 and NfL concentrations differ across clinical diagnoses in an unselected, real‐world memory clinic cohort.MethodWe included 418 consecutive patients from the Amsterdam Dementia Cohort. Patients were split among 12 diagnoses, including SCD, Mild Cognitive Impairment (MCI), probable AD, Dementia with Lewy Bodies (DLB) and FTD (Table 1). pTau‐217 was measured using the novel AlzPath assay, while NfL was measured using the Quanterix Simoa assay. were used to classify patients as high or low for pTau‐217 and NfL levels. The pTau‐217 cutoff (0.58 pg/mL) was the Youden index cutoff derived from the present data, based on amyloid‐positive AD vs amyloid‐negative SCD diagnosis (n = 57), using amyloid status derived from cerebrospinal fluid or Amyloid positron emission tomography for classification. (18.2 pg/mL) was chosen based on the sample’s median age (64 years) and taking the value associated with the 90th percentile of normal NfL levels (NfL interface for physicians (shinyapps.io)).ResultpTau‐217 levels were highest in patients with AD and Primary Progressive Aphasia (PPA), and lowest in those with Vascular Dementia (VaD) and other neurological diagnosis (Figure 1). NfL levels were highest in patients with VaD and FTD, and lowest in SCD and psychiatric diagnoses. The cutoffs highlighted similar trends, with higher proportions patients with elevated pTau‐217 levels observed in possible and probable AD, MCI, and DLB. Higher proportions of patients with high NfL levels were observed in FTD, PPA, VaD, and possible AD (Figure 2).ConclusionpTau‐217 concentrations vary as expected across the different diagnoses, with highest concentrations in AD pathology diagnostic groups. The elevated levels observed in DLB and PPA could be due to underlying AD co‐pathology. Following previous results, NfL concentrations were highest in FTD and lowest in psychiatry and SCD.

A comparative study of posterior cingulate metabolism in patients with mild cognitive impairment due to Parkinson's disease or Alzheimer's disease

Few comparative studies have assessed metabolic brain changes in cognitive impairment among neurodegenerative disorders, and the posterior cingulate cortex (PCC) is a metabolically active brain region with high involvement in multiple cognitive processes. Therefore, in this study, metabolic abnormalities of the PCC were compared in patients with mild cognitive impairment (MCI) due to Parkinson’s disease (PD) or Alzheimer’s disease (AD), as examined by proton magnetic resonance spectroscopy (1H-MRS). Thirty-eight patients with idiopathic PD, including 20 with mild cognitive impairment (PDMCI) and 18 with normal cognitive function (PDN), 18 patients with probable mild cognitive impairment (ADMCI), and 25 healthy elderly controls (HCs) were recruited and underwent PCC 1H-MRS scans. Compared with HCs, patients with PDMCI exhibited significantly reduced concentrations of N-acetyl aspartate (NAA), total NAA (tNAA), choline (Cho), glutathione (GSH), glutamate + glutamine (Glx) and total creatine (tCr), while ADMCI cases exhibited significantly elevated levels of myo-inositol (Ins) and Ins/tCr ratio, as well as reduced NAA/Ins ratio. No significant metabolic changes were detected in PDN subjects. Compared with ADMCI, reduced NAA, Ins and tCr concentrations were detected in PDMCI. Besides, ROC curve analysis revealed that tCr concentration could differentiate PDMCI from PDN with an AUC of 0.71, and NAA/Ins ratio could differentiate patients with MCI from controls with normal cognitive function with an AUC of 0.74. Patients with PDMCI and ADMCI exhibited distinct PCC metabolic 1H-MRS profiles. The findings suggested cognitively normal PD patients with low NAA and tCr in the PCC might be at risk of preclinical PDMCI, and Ins and/or NAA/MI ratio in the PCC should be reconsidered a possible biomarker of preclinical MCI in clinical practice. So, comparing PCC’s 1H-MRS profiles of cognitive impairment among neurodegenerative illnesses may provide useful information for better defining the disease process and elucidate possible treatment mechanisms.

Magnetoencephalography(MEG) spectral signature of cognitive impairment ‐ A perspective on pathophysiological changes with blood pressure

AbstractBackgroundSpectral ratios (e.g., resting‐state EEG alpha/theta power ratio), which index rhythmic brain activity, have been shown to distinguish early‐onset AD from healthy controls. Magnetoencephalographic (MEG) brain imaging offers advantages over EEG through its unique combination of excellent temporal as well as spatial precision for detecting brain activity. The purpose of this study is to compare MEG spectral activity in cognitively impaired and healthy controls with changes in systolic blood pressure (sbp), specifically focused in the frontal lobe as this region is known to be susceptible to hypertension related white matter degradation.MethodsSixteen cognitively impaired, including 13 possible and 3 probable mild cognitive impairment (MCI), (mean age 65.6 years, males/females: 5/11, Whites/Blacks: 11/5) and sixteen age, sex, and race matched healthy controls (mean age 62.4 years, males/females: 4/12, Whites/Blacks: 11/5) were recruited from an ongoing multiethnic community‐based study to complete six minutes of resting‐state MEG along with a T1w brain MRI. All MEG data underwent standard preprocessing. Resultant whole‐brain maps of spectral activity were filtered into six canonical frequency bands, including delta (2‐4 Hz), theta (5‐7 Hz), alpha (8‐12 Hz), beta (15‐29 Hz), gamma (30‐59 Hz) and high gamma (60‐90 Hz). Relative mean power of each frequency band, and spectral ratios of alpha/theta, beta/delta as well as a spectral slowing index [(alpha+beta+gamma)/(delta+theta)] were computed.ResultMean sbp was 135 mm Hg for both groups. Generalized linear regression models showed cognitive impairment was negatively associated with spectral ratios beta/delta and spectral slowing index. We also found a significant positive association between spectral ratios (beta/delta β = ‐0.0115, p = 0.0015; spectral slowing index β = ‐0.0125, p = 0.0144) and interaction of systolic blood pressure with cognitive impairment. Results are summarized in tables 1‐2.ConclusionLower spectral ratios have previously been demonstrated in individuals with AD. Somewhat surprisingly, our findings indicate that lower blood pressure is associated with lower values on these MEG metrics in cognitively impaired individuals. Interestingly, overtreatment of hypertension in elderly with MCI has been associated with greater cognitive decline. Thus, these results will be examined in a larger cohort and the analysis will be expanded to include anti‐hypertensive medication data to potentially explain the above findings.

Screening for MCI in the Swedish H70 Birth Cohort Study using digital automatic speech biomarker tests for cognition and a machine Learning classifier

AbstractBackgroundEven if classic neuropsychological tests often have excellent psychometric properties to detect Mild Cognitive Impairment (MCI), they are not suitable for cost‐effective low‐burden screening at scale. Speech‐based digital biomarkers can be deployed in a highly automated fashion. We present the results of an MCI screening algorithm based on a digital Speech Biomarker for Cognition (SB‐C) in the Swedish H70 birth cohort study.MethodWe used a sample from the Swedish H70 Birth Cohort study (N = 404; 356 cognitively healthy (HC), 48 MCI). We automatically extract the SB‐C score and its subscores (executive function, memory, semantic memory, processing speed) from SVF and RAVLT speech recordings using ki:elements’ proprietary speech analysis pipeline including automatic speech recognition and feature extraction. We performed (1) inferential statistics comparing MCI and HC group based on the biomarker scores and (2) built a machine learning model to screen for MCI. For (1) we performed a non‐parametric Kruskal‐Wallis test to compare SB‐C scores of both HC and MCI groups to check for general feasibility. For (2), we trained a support vector machine model with class weights and leave‐one‐out cross validation to classify between MCI and HC using the SB‐C scores as input (overall score and the subscores).ResultThere was a group difference for the SB‐C aggregated cognition score between the groups (HC &gt; MCI; χ2 = 45.9 (1), p &lt;0.001; Figure 1), and also for the subscores (Table 2). To classify between MCI and HC, using a feature selection method, the best model was found for all the five biomarker scores selected with an Area Under Curve of 0.77 (Figure 2), a specificity of 0.77 and a sensitivity of 0.76 (Table 3).ConclusionWe found that a machine learning‐based screening algorithm based on the SB‐C can detect probable MCI patients in representative population sample of older people using a speech biomarker read‐out.

Abstract 9705: Diastolic Blood Pressure and Intensive Blood Pressure Control on Cognitive Outcomes: Insights From the SPRINT Trial

Introduction: The potential benefits or harms of intensive systolic blood pressure (SBP) lowering on cognitive function in individuals with low diastolic blood pressure (DBP) remain unclear. Hypothesis: The effects of intensive SBP lowering on cognitive outcomes were consistent across baseline DBP levels. Methods: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 8563 participants with at least one follow-up cognitive assessment were included. Cognitive outcomes were the occurrence of probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models and likelihood ratio tests were used to assess the interaction between DBP quartiles and intensive SBP control on cognitive outcomes. Results: The incidence rates of cognitive outcomes among participants in the lowest DBP quartile were higher than those in the other three DBP quartiles (Figure 1). However, participants in the intensive group had a lower incidence rate of probable dementia or MCI than those in the standard group, regardless of DBP quartiles. There were no significant interactions between SBP intervention and DBP quartiles for probable dementia ( P for interaction =0.06), MCI ( P for interaction =0.80), or a composite of probable dementia or MCI ( P for interaction =0.24) (Figure 2). Conclusions: In this post hoc analysis of the SPRINT study, patients with lower DBP had a higher incidence of cognitive impairment. However, the effects of intensive SBP lowering on cognitive outcomes were consistent across different DBP groups.

Abstract 10180: Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT Trial

Introduction: Systolic blood pressure (SBP) time in target range (TTR) was proven to be a new parameter to predict cardiovascular outcomes. However, the prognostic value for cognitive function is unclear. Hypothesis: Higher TTR was associated with lower incidence of cognitive outcomes. Methods: We performed a post hoc analysis from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized controlled trial comparing intensive (&lt;120 mm Hg) and standard (&lt;140 mm Hg) SBP interventions in 9361 individuals with hypertension. SBP target range was defined as 110 to 130 mm Hg for the intensive group and 120 to 140 mm Hg for the standard group. Participants who had less than 3 SBP measurements during this period or no cognitive assessment in the follow-up were excluded. TTR was calculated by linear interpolation using SBP from baseline to the first 3 months of follow-up. Cognitive outcomes were probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models were used to evaluate the relationship between TTR and cognitive outcomes. Results: A total of 8415 patients were included in this study. In univariate Cox regression analysis, higher time in target range was associated with lower risk of probable dementia. After adjustment for age, sex and race, a 1-SD increase in TTR was independently associated with a 16% lower risk of probable dementia (hazard ratio [HR] =0.84, 95% CI 0.75-0.93, P =0.002) (Figure). When we further added demographics, medical history and mean SBP to the multivariate Cox regression model, TTR remained significantly associated with a decreased risk of probable dementia (HR =0.84, 95% CI 0.74-0.96, P =0.012). No significant relationship was found between TTR and MCI or a composite of probable dementia or MCI. Conclusions: In this post hoc analysis of the SPRINT trial, SBP time in target range was an independent predictor of probable dementia beyond mean SBP levels.

The association of sleep and cortical thickness in mild cognitive impairment.

We investigated whether device-measured sleep parameters are associated with cortical thickness in older adults with probable mild cognitive impairment (MCI). We performed a cross-sectional, exploratory analysis of sleep and structural MRI data. Sleep data were collected with MotionWatch8© actigraphy over 7days. We computed average and variability for sleep duration, sleep efficiency, and fragmentation index. T1-weighted MRI scans were used to measure cortical thickness in FreeSurfer. We employed surface-based analysis to determine the association between sleep measures and cortical thickness, adjusting for age, sex, Montreal Cognitive Assessment (MoCA) score, and sleep medication use. Our sample included 113 participants (age=73.1 [5.7], female=72 [63.7%]). Higher fragmentation index variability predicted lower cortical thickness in the left superior frontal gyrus (cluster size=970.9mm2, cluster-wise p=0.017, cortical thickness range=2.1mm2 to 3.0mm2), adjusting for age, sex, MoCA, and sleep medication. Our results suggest that higher variability in sleep fragmentation, an indicator of irregular sleep pattern, is linked to lower cortical thickness. Future longitudinal studies are needed to determine the directionality of these associations.

Effects of cognitive impairment and depressive symptoms on health-related quality of life in community-dwelling older adults: The mediating role of disability in the activities of daily living and the instrumental activities of daily living.

The objective of this study was to estimate the joint effects of cognitive impairment and depressive symptoms on health-related quality of life (HRQoL) and to explore the mediating role of disability among Chinese community-dwelling older adults. A cross-sectional study was conducted with 2525 community-dwelling older adults aged ≥60 years and living in Shanghai, China in 2019. Participants were divided into four groups: (1) non-depressed without dementia, (2) non-depressed with probable MCI, (3) depressed without dementia and (4) depressed with probable mild cognitive impairment (MCI). HRQoL was assessed using the 36-Item Short-Form Health Survey. Cognitive impairment and depressive symptoms were evaluated with the AD8 and the Geriatric Depression Scale respectively. Activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and other sociodemographic variables were also assessed. The results of this study showed that controlling for sociodemographic characteristics, significant differences in a physical component score (PCS) and a mental component score (MCS) of HRQoL were found across the four groups. Compared to those who were non-depressed without dementia, older adults who were depressed with probable MCI reported the lowest level of PCS and MCS, followed by older adults who were depressed without dementia. Both ADL and IADL disabilities played mediating roles in the relationship between cognitive impairment and depressive symptoms and PCS. Based on this study, we suggest that the early detection and adequate management of depressive symptoms and cognitive status-as well as efforts to improve individuals' ability to manage their ADLs and IADLs-may help to maintain or improve their HRQoL.

Frequency and correlates of mild cognitive impairment and dementia among the oldest old – Evidence from the representative “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)”

ObjectivesSince there is limited knowledge with regard to the frequency and correlates of mild cognitive impairment and dementia among the oldest old based on large representative data (including institutionalized individuals), our objective was to fill this research gap. MethodsFor our study, data came from the representative “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)”. This study included community-dwelling and institutionalized individuals aged 80 years and over (n = 1,173, mean age: 86 years) residing in the most populous state of Germany (North Rhine-Westphalia). The DemTect was used to quantify cognitive impairment (i.e., probable mild cognitive impairment and probable dementia). ResultsOverall, 73.1% of the individuals were not cognitively impaired, 17.0% of the individuals had probable mild cognitive impairment and 9.9% of the individuals had probable dementia. Compared to individuals without cognitive impairment, individuals with probable mild cognitive impairment were more likely to be male, live in an institutionalized setting, have a lower educational level, have a smaller network size, and have lower functional abilities. Moreover, compared to individuals without cognitive impairment, individuals with probable dementia were more likely to be older, live in an institutionalized setting, have a lower educational level, have a smaller network size, not be multimorbid, and have lower functional abilities. ConclusionsOur study identified several sociodemographic and health-related factors which are associated with probable mild cognitive impairment and probable dementia among the oldest old. This knowledge may help to address individuals at risk for mild cognitive impairment and dementia.

The age differences and effect of mild cognitive impairment on perceptual-motor and executive functions.

It is unclear whether the decline in executive function (EF) and perceptual-motor function (PMF) found in older adults with mild cognitive impairment (MCI) is the result of a normal aging process or due to MCI. This study aimed to determine age-related and MCI-related cognitive impairments of the EF and PMF. The EF and PMF were investigated across four groups of 240 participants, 60 in each group, including early adult, middle adult, older adult, and older adult with probable MCI. The EF, working memory, inhibition, and cognitive flexibility were evaluated using digit span backward tasks, the Stroop color-word test, and the modified switching verbal fluency test, respectively. The PMF, visual perception, visuoconstructional reasoning, and perceptual-motor coordination were evaluated using the clock reading test, stick design test, and stick catching test, respectively. Group differences were found for all subdomains of EF and PMF (p < 0.05), except for perceptual-motor coordination, indicating that this subdomain could be maintained in older adults and was not affected by MCI. For the age difference, working memory, cognitive flexibility, visual perception, and visuoconstructional reasoning remained stable across middle adults and started to decline in older adults, while cognitive inhibition began to decrease in middle adults and it further declined in older adults. To control the confounding effect of education level, the results showed that only cognitive flexibility was further decreased in older adults with probable MCI compared to those without MCI (p < 0.05). In conclusion, cognitive inhibition decreased earlier in middle adults, whereas EF and PMF started to decline in older adults. Cognitive flexibility was the only MCI-sensitive cognitive function.

Objective Sleep Quality and the Underlying Functional Neural Correlates Among Older Adults With Probable MCI

Poor sleep is a strong risk factor for dementia and is commonly reported among older adults with mild cognitive impairment (MCI). However, the neural underpinnings of poor sleep among older adults with MCI remains equivocal. The goal of this cross-sectional analysis was to explore the relationship between resting-state functional connectivity in the brain and sleep quality as measured by actigraphy. We hypothesize lower sleep efficiency and higher sleep fragmentation may be associated with aberrant functional connectivity of brain regions involved in somatosensory, somatomotor, and attentional processing. Thirty-six community-dwelling older adults with probable MCI between 65-85 years (mean=71.8 years) were assessed for sleep quality using a motion watch to quantify sleep efficiency and fragmentation over 14 days. All participants completed resting-state functional magnetic resonance imaging (fMRI) within 14 days of sleep monitoring. Independent associations between network connectivity and sleep quality were determined using general linear models. Examined networks included the somatosensory network (SMN), dorsal attention network (DAN), ventral attention network (VAN), frontoparietal network (FPN), and default mode network (DMN). Mean Montreal Cognitive Assessment score was 22.5 (SD=2.7) and Mini-Mental State Examination score was 28.3 (SD=1.5). Mean sleep efficiency and fragmentation index was 80.1% and 31.8 respectively. Higher sleep fragmentation correlated with increased connectivity between the SMN and insula, the SMN and posterior cingulate, as well as FPN and primary motor area (Z=3.1; p<0.05). These results suggest aberrant functional connectivity between brain regions involved in attentional and somatosensory processes may be associated with disrupted sleep mechanisms in older adults with MCI.

BIOFACE: A prospective study of risk factors, cognition and biomarkers in a cohort of individuals with early‐onset mild cognitive impairment at Fundació ACE

AbstractBackgroundThe diagnosis of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) is based on either cerebrospinal fluid (CSF) or neuroimaging biomarkers (Albert et al, 2011). Currently, several non‐invasive and cheaper blood‐based biomarkers are being investigated, including neuronal‐derived plasma exosomes (NPEs) (Winston et al, 2016). The role of neuroinflammation, oxidative stress and early vascular changes, prior to the onset of amyloidosis, has been described in the pathogenesis of AD (Iturria‐Medina et al, 2016) and vascular‐related proteins can be traced in plasma and NPEs using proteomics. However, these changes have not been studied in early onset MCI (EOMCI), that is, when symptoms begin under the age of 65 (Rossor et al, 2010).ObjectiveTo describe the rationale, study design and baseline characteristics of the BIOFACE cohort, a two‐year prospective observational study on EOMCI conducted at Fundació ACE in Barcelona, Spain. The study goal is to characterize different clinical, neuropsychological and biomarker phenotypes and to investigate CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD.MethodParticipants underwent neurological and neuropsychological batteries and multimodal biomarkers including brain MRI, APOE genotyping, plasma and NPEs, saliva, CSF, non‐invasive arterial peripheral testing, anthropometrics and neuro‐ophthalmological examinations. In the final visit, participants will undergo brain MRI, lumbar puncture and blood extraction for NPEs.ResultNinety‐seven patients with EOMCI were recruited. Most participants were women (59.8%). Mean age at symptom onset was 57 years; mean MMSE score was 28 with a mean of 12.13 years of education. First degree and presenile family history of dementia was present in 60.8% and 15.5%, respectively. Depressive and anxiety disorders, along with vascular risk factors, were the most frequent comorbidities. Syndromic diagnoses were established: possible amnestic MCI (n=32), possible non‐amnestic MCI (n=33), probable amnestic MCI (n=16) and probable non amnestic MCI (n=16). CSF biomarkers (ATN classification): A+ (n=15), A‐T/N+ (n=13), A‐T‐N‐ (n=57).ConclusionBIOFACE is a two‐year observational study of cognition and biomarkers that will shed light on the physiopathology and the potential utility of plasma proteomics and NPEs as non‐invasive early diagnostic and prognostic biomarkers in individuals with early onset MCI.

Prevalencia de probable deterioro cognitivo en adultos mayores de una población mexicana utilizando el MMSE y el MoCA

ABSTRACT Background: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are screening instruments frequently used to detect probable mild cognitive impairment (MCI). The MoCA has shown greater sensitivity and specificity in the clinical population than the MMSE. However, the proportion of people with MCI using the MoCA may be overestimated in the community. Therefore, the objective is to identify in older adults in the community in Mexico City the prevalence of probable DCL using the MoCA and the MMSE. Method: A cross-sectional descriptive study was carried out, in a sample of 231 participants belonging to community groups with an age between 55 and 90 years and schooling from 0 to 22 years; MMSE and MoCA were applied. Results: a score is obtained in MMSE of 25.0 ± 3.1 and in MoCA of 19.8 ± 5.4 with a moderate correlation (r = 0.59, p < 0.05) between them. 84% of the population using MoCA and 23.8% of the population using MMSE are classified as likely MCI. Conclusion: The MMSE can give an estimate more similar to what is reported in the literature than the MoCA in the community. The implications in public policies, in clinical use and in research of an overestimation in the proportion of people with probable MCI are discussed.