State Examination Research Articles

Associations of time in bed and sleep timing with dementia and cognitive decline among Chinese rural‐dwelling older adults: A cohort study

AbstractBackgroundThe longitudinal associations of time in bed (TIB) (a composite indicator of sleep duration, latency, and fragmentation) and sleep timing (a marker of circadian rhythms) with dementia and cognitive decline in older adults are unclear.MethodThis population‐based cohort study used data from 1982 participants in the Shandong Yanggu Study of Aging and Dementia, who were aged ≥60 years, free of dementia, and living in the rural communities in western Shandong Province, China. At the baseline (2014) and follow‐up (2018) examinations, sleep parameters were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Global cognitive function was measured using the Mini‐Mental State Examination (MMSE). Dementia was diagnosed following the DSM‐IV criteria, and the NIA‐AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional‐hazards models, and general linear models.ResultDuring the mean follow‐up of 3.7 (standard deviation = 0.3) years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J‐shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J‐shaped association with mid‐sleep time. When continuous sleep parameters were categorized into tertiles, the multivariable‐adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01‐2.83) for baseline sleep duration >8 hours (vs. 7‐8 hours), 2.17 (1.22‐3.87) for bedtime before 9PM (vs. 10PM or later), and 2.00 (1.23‐3.24) for mid‐sleep time before 1AM (vs. 1‐1.5AM). Early bedtime and mid‐sleep time were significantly associated with incident AD (multivariable‐adjusted HR range: 2.25‐2.51; P<0.05). Among individuals who were free of dementia at follow‐up, baseline long TIB, early bedtime and mid‐sleep time, early and late rise time, and prolonged TIB and advanced mid‐sleep time from baseline to follow‐up were associated with greater decline in MMSE score (P<0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged <75 years.ConclusionLong TIB and early sleep timing are associated with an increased risk of dementia and AD, and their associations with greater cognitive decline are evident only among young‐old people and men.

The effect of virtual reality and physical exercise training on cognitive function in older adults with mild cognitive impairment

AbstractBackgroundNumerous studies have shown that aerobic and resistance exercises, including leisure time physical activity help to reduce the risk of cognitive decline. Recently potential of cognitive training using immersive virtual reality (VR) has been growing in the non‐pharmacological interventions for mild cognitive impairment (MCI). However, there are not enough studies comparing the impact of two different interventional approaches on cognition and brain function especially on MCI patients. Therefore, we investigated the effectiveness of two non‐pharmacological intervention using VR and aerobic‐and resistance physical exercise (PE) on cognitive and brain function of older adults with MCI.MethodThis study included 99 participants (70.8 ± 5.4) with MCI randomly assigned to PE, VR, and control group. The PE training consisted of aerobic and resistance exercise performed for 50 mins 5 times/week for 12 weeks. The immersive VR‐based cognitive training consisted of series of cognitive games. 24 sessions of VR training (three days/week) were performed, and each session was 100 mins long. Global cognitive function was measured with Mini‐Mental State Examination (MMSE) test. Resting‐state electroencephalography (EEG) of neural oscillatory activity in different frequency bands was measured. Physical function was measured with hand grip strength (HGS), gait speed and timed up and go test.ResultAfter the intervention period, VR significantly enhanced global cognition (p<0.045) and HGS (p<0.001) whereas PE significantly improved HGS (p<0.001) compared to baseline. One way Analysis of variance (ANOVA) of resting state EEG showed decreased theta/beta power ratio (TBR) (p<0.018) in the central region of the brain in PE group compared to the control group. Although not significant, VR group also showed decreased TBR compared to control group.ConclusionOur study findings suggest that VR based cognitive training enhances both global cognition and physical function of older adults with MCI. The decrease in resting state TBR in PE and VR group also indicated improved attention. Further studies should peruse the effect of VR exergaming intervention, a combination of PE and cognitive games, to yield peak benefits on MCI patients.

Comparing visuospatial construction ability of MoCA and MMSE in cognitive assessment of patients with dementia of Alzheimer’s type

AbstractBackgroundThe ability to see an object or picture as a set of parts and then to construct a replica of the original from these parts is known as visuospatial constructive cognition. Examples of visuospatial construction include drawing, buttoning shirts, constructing models, making a bed, and putting together furniture that arrives unassembled. Visuospatial construction is a central cognitive ability. At the same time, there are enormous individual differences among people in their ability to perform visuospatial constructive tasks. The MoCA had greater sensitivity than MMSE in detecting MCI versus HCs (; however, specificity was lower for the MoCA than MMSE.MethodThe present study has considered visuospatial construction ability in cognitive neuropsychological screening tool. The neuropsychological screening tool were Mini‐mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The intersecting pentagons copy sub‐item was administered as part of the MMSE whereas there was cube figure to copy where subjects have to initially convert a two‐dimensional contour to a three‐dimensional cube. The sample consisted of 15 patients with mild Dementia of Alzheimer’s type.ResultThe result showed that both the MoCA and the MMSE were successful in differentiating between patients with and without cognitive domain deficits and cognitive impairment. The scores in visuospatial construction ability on MoCA and MMSE are different on visuospatial domain which on further analysis showed significant differences in cognitive performance.ConclusionThe cognitive scores of mild Dementia of Alzheimer’s patient differs which showed the differences in the ability to complete a cognitive task as and thus revealed greater sensitivity of MoCA as compared to MMSE.

Four‐year cognitive decline in mild cognitive impairment patients with distinct baseline neuroanatomical atrophy profiles: A MEMENTO and QyScore® study

AbstractBackgroundNeuroanatomical atrophy profile is increasingly recognised as a valuable characterisation in mild cognitive impairment (MCI) individuals and may provide prognostic information about cognitive decline.Method1153 MCI participants from the MEMENTO memory clinic study with 48‐month longitudinal follow‐up were included (mean (sd) Age = 70.6 (8.2), 60% female, CDR‐SB = 0.63 (0.72)). QyScore® volumetric quantification was applied to baseline 3DT1 images and four recognized neuroanatomical subtypes defined based on regional atrophy with respect to an internal normative database (z←1.64) [1,2]: no/minimal atrophy [N‐] (n = 1,012), limbic predominant: LP (n = 37), hippocampal sparing: HS (n = 84) and combined hippocampal and cortical atrophy [typical/diffuse: TD] (n = 20). 145 participants were amyloid positive (A+) via CSF or PET (Age = 73.7 (5.9): 47% female: N‐ = 114, LP = 8, HS = 21 and TD = 2). All participants underwent cognitive and functional assessments at baseline and 48 months, including mini‐mental state examination (MMSE), clinical dementia rating (CDR), Free and Cued Selective Reminding Test (FCRST) and Instrumental Activities of Daily Living (IADL) scale. Linear regression analysis (correcting for age, sex and baseline performance) investigated the relationship between baseline neuroanatomical subtype and subsequent 4‐year cognitive decline. Bonferroni correction was applied.ResultAt month 48, all subtypes demonstrated significant decline across memory, orientation, and executive function. Severity of decline varied across subscales and subtype and was particularly marked in A+ LP individuals (Figure 1). IADL remained stable for the N‐ and TD subgroups. 143 participants converted to dementia [102 = N‐, 18 = LP, 15 = HS, and 8 = TD subtypes, representing 10%, 49%, 18% and 40% of the total N‐, LP, HS and TD atrophy subtypes respectively]. HS and N‐ individuals also demonstrated the least decline across all domains and did not significantly differ on any tests. LP atrophy subtype demonstrated the greatest decline across all cognitive domains as well as global CDR and IADL (p<0.001 compared with N‐ and HS subtypes). Similarly, TD phenotypes showed significant decline across multiple cognitive subscales compared with N‐ and HS subtypes (p<0.001) particularly for orientation and global CDR.ConclusionEarly atrophy profiles in MCI populations can provide insights into the domains and severity of future patient progression over 4 years.[1] Planche et al., (2020)[2] Schwarz et al., (AAIC2022)

Fecal microbiota transplant can improve cognition in patients with cognitive decline and Clostridioides difficile infection

AbstractBackgroundAfter fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline.MethodThe study included 10 patients (age range, 63‐90 years; female, 80%) with dementia and severe CDI who were evaluated using cognitive function tests (Mini‐Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR‐SB] score) and stool PCR before and after FMT. Cognitive function test was performed one month before FMT and one month after FMT. The patients’ fecal samples were analyzed to determine the composition of their gut microbiota before FMT and 3 weeks after FMT to compare the microbiota composition.ResultTen patients receiving FMT showed improvements in clinical symptoms and cognitive functions. The MMSE score pre‐FMT was 10.00 (Median, 7.00 – 14.00 interquartile range [IQR]), and the MMSE score post‐FMT was 16.00 (Median, 13.00 – 18.00 [IQR]). The CDR‐SB score pre‐FMT was 10.00 (Median, 5.00 – 12.00 IQR), and post‐FMT was 5.50 (Median, 4.00 – 8.00, IQR). FMT led to changes in the recipient’s gut microbiota composition, with enriched Proteobacteria in pre‐FMT and Bacteroidetes in post‐FMT most pronounced. We found that the genera were reported to be associated with cognitive function. In addition, alanine, aspartate, and glutamate metabolism pathway was found to be significantly different between before and after FMTConclusionThis study highlight the important interaction between the gut microbiome and cognitive function. Moreover, this study suggest that FMT may effectively delay cognitive decline in patients with dementia.

Relationship between blood pressure and cognitive decline in normal cognitive population: A four‐year follow‐up study in rural Xi'an

AbstractBackgroundHypertension is a modifiable risk factor for cognitive impairment, although the relationship between hypertension and cognitive impairment is not fully understood. The objective of to clarify the relationship between blood pressure and cognitive decline in cognitive normal population through a longitudinal follow‐up study.MethodCognitively normal population was selected from people who lived in the suburbs of Xi’an, China.The mini‐mental state examination (MMSE) and neuropsychological battery were used to assess cognition. Four years later, MMSE was tested again and cognitive decline was defined as a decrease in MMSE scores ≥2 points.The relationship between blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP),] and cognitive impairment was analyzed by logistic regression models using interaction and stratified analysis. Blood pressure and age were regarded as both continuous and categorical data。ResultA total of 1024 participants completed the study, among whom 168 subjects (16.41%) presented cognitive decline.Interaction analysis for the total population showed that SBP (when regarded as continuous data) was positively correlated with cognitive impairment (OR = 1.173 [95% CI,1.030‐1.335] per 10mmHg, P = 0.016); however, the age by SBP interaction term was inclined to be negatively correlated with cognitive impairment (OR = 0.850 [95% CI, 0.711–1.016] per10mmHg×year, P = 0.074), indicating that the relationship between SBP and cognitive impairment was age‐dependent. When the blood pressure and age were considered as binary data, the results were similar to those obtained when they were considered as continuous variables.Stratified multivariate analysis revealed that the relationship between SBP (when regarded as continuous data) and cognitive impairment was positive for patients aged 50‐59 years (OR = 1.209 [95% CI:1.025–1.427] per 10mmHg, P = 0.024).However, positive results were not obtained for DBP and MABP.ConclusionElevated blood pressure is positively correlated with cognitive impairment in the middle age(50‐59), but this positive association declines with increasing age.

Simplify scales for identifying AD and MCI: A machine learning study based on six years of database

AbstractBackgroundAlzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive functional decline accompanied with neuropsychiatric symptoms and impairment of activities of daily living (ADL). Mild Cognitive Impairment (MCI) is considered the prodromal state of AD. Early identification of MCI is a strategy to reduce the burden of caregivers and society. Neuropsychological scales are still the most used method for identification of cognitive decline. The purpose of this study was to simplify the scales by eliminating some insensitive items based on the six years of database and machine learning methods.MethodA total of 458 patients newly diagnosed as AD or MCI were recruited in Memory Clinic, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University from 2014 to 2019. Neuropsychological battery was used to evaluate the cognitive function, neuropsychiatric symptoms and ADL, including Mini‐mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Boston Naming Test (BNT), Digit Span (DS), Auditory Verbal Learning Test (AVLT), Trail Marking Test (TMT) A and B. Alzheimer’s Disease Assessment Scale (ADAS‐cog), Clinical Dementia Rating (CDR), Instrumental Activity of Daily Living Scale (IADL), Physical Self‐Maintenance Scale (PSMS). XGboost and CART regression tree were used to test all items contained in all scales and try to explore the importance of each item. Sensitivity was reflected by the AUC (Area Under Curve).ResultOf which 236 patients were diagnosed as AD and 222 as MCI. The mean age was 72.99±9.04 years and 51.53% were male. Among all the battery items, ADAs‐cog word recognition task showed the best importance in judging AD and MCI, followed correct numbers of AVLT delay recall, ADAs‐cog orientation, MMSE recall, TMT‐B time. The overall sensitivity for predicting AD or MCI for all items was 0.83. However, in our preliminary screening also showed the 31 items, most of which were based on the ADL scale and neuropsychiatry symptoms, contributed little to distinguishing AD from MCI. After removed these items, the sensitivity became to 0.87.ConclusionCognitive assessment such as recall and orientation may be a better strategy than neuropsychiatric symptoms and ADL when identifying AD from MCI.

Neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease: Relation with disease stage, sex, and daily function impairment

AbstractBackgroundTo reveal the relations between neuropsychiatric symptoms (NPS), stages of cognitive impairment, sex, and daily function impairment in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).Method1,154 patients with MCI and AD were enrolled from 2014 to 2021 from the Memory Clinic, The First Affiliated Hospital of Chongqing Medical University. Mini‐mental State Examination (MMSE) was used to assess the cognitive function, and Clinical dementia rating scale (CDR) was used to evaluate the disease severity of patients. NPS and function of patients’ daily life were evaluated by Neuropsychiatric Inventory (NPI) and activities of daily living (ADL) respectively.ResultPsychosis symptoms displayed the highest prevalence in MCI (43.3%) and mild AD stage (62.2%), while in moderate and severe AD, behavior symptoms showed its dominance (86.7% and 96.4%, respectively). Delusion, apathy, AMB and sleep disturbance were the discriminant symptoms across the spectrum of cognitive decline (all P <0.05). Depression was more prominent in female (26.1% vs. 14.9% in MCI; 40.2% vs. 21.0% in AD, all P< 0.05) while male patients presented higher prevalence in apathy (27.0% vs. 18.6% in MCI; 54.1% vs. 42.8% in AD, all P< 0.05). Physical self‐maintenance was negatively impacted by apathy and sleep disturbance at mild AD stage, while instrumental activity of daily living was significantly influenced by aberrant motor behavior in MCI and mild AD (all P< 0.05).ConclusionThe prevalence of NPS is correlated with sex, the stage of cognitive impairment and daily living function. Revealing their relations can allow he development of better prevention and treatment strategies for patients with cognitive impairment.

68969: Comparative Study Of Neuropsychology、MRI and 18F‐FDG PET in Patients with Alzheimer’s Disease and Semantic Dementia

AbstractBackgroundConfusion between Alzheimer’s disease (AD) and semantic dementia (SD) in early diagnosis is common, and most previous studies have been based on clinical diagnoses without a pathological diagnosis by biomarkers.Method15 patients 18F‐AV 45 PET (+) with AD and 9 patients 18F‐AV 45 PET (‐) with SD enrolled. All patients underwent the following examinations: (1) Neuropsychological tests, including Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Boston Nomenclature Test (BNT), and Neuropsychiatric Scale table (NPI). (2) 3.0 head MRI examination, the imaging results were evaluated by MTA‐Scale, Koedam scale, and Kipps scale. (3) 18F‐FDG PET examination, PET images were quantitatively analyzed by Neuro Q software.ResultADL score increased in both groups, and the ADL score in the AD group was higher than that in the SD group (P = 0.035). BNT score decreased in both groups, but the BNT score in the SD group was lower than that in the AD group (P = 0.013). There were differences between the two groups in several psycho‐behavioral symptoms; delusions symptoms in the AD group were more prominent than those in the SD group (P = 0.009), and euphoria and disinhibition symptoms in the SD group were more pronounced than AD group (P = 0.015 and 0.015, respectively). The MRI atrophy rating scale showed that the left hippocampus, left frontal lobe, left anterior, and posterior temporal lobe atrophy in the SD group was more severe than that of the AD group (P = 0.018, 0.018, 0.022, and 0.044, respectively). Compared with the two groups of patients, the brain regions with significantly decreased metabolism in the AD group included the right inferior parietal lobule, right posterior cingulate gyrus, and left posterior cingulate gyrus (P = 0.037, 0.014, and 0.037, respectively); the brain regions with significantly decreased metabolism were left inferior frontal gyrus, left medial anterior temporal lobe, right medial anterior temporal lobe, left inferior lateral temporal lobe and left caudate nucleus (P = 0.017, 0.003, 0.037, 0.003, and 0.017, respectively).ConclusionNeuropsychology, brain structure, and brain metabolism aid in AD and SD differential diagnosis.

Application of the modified qualitative scoring of MMSE pentagon test in the differential diagnosis of lewy body dementia and Alzheimer’s disease

AbstractBackgroundTo explore the value of the modified qualitative scoring of MMSE pentagon test (mQSPT) in the differential diagnosis of Lewy body dementia (DLB) and Alzheimer’s disease (AD).MethodStudy the patients who met the inclusion criteria in the Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2018 to August 2021. The baseline data of gender, age and education, Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA) and Clinical Dementia Assessment Scale (CDR) scores of 61 DLB patients and 71 AD patients were analyzed retrospectively. At the same time, the scores of sub items in the scale that can reflect visualspatial impairment were recorded,: i.e. connection test, cube copy, clock drawing test in MoCA, and pentagon copy test in MMSE. The images in MMSE pentagon copy test of these patients were further scored according to QSPT and mQSPT, and compared between the two groups. Multivariate stepwise logistic regression was used to analyze the differential efficacy of QSPT, mQSPT combined with other clinical psychological evaluation between DLB and AD.ResultThere were significant differences between DLB and AD patients in connection test, cube copy, clock drawing test, pentagon copy test, QSPT, mQSPT and gender, but there were no significant differences in MMSE, MoCA, age and education. The sensitivity of QSPT in differentiating DLB and AD was 71.8%, the specificity was 67.2%, the area under ROC curve was 0.682 (95%CI: 0.584‐0.772), and the cut‐off value was 9.5. The sensitivity of mQSPT in differentiating DLB and AD was 68.9%, the specificity was 84.5%, the area under ROC curve was 0.78 (95%CI: 0.696‐0.862), and the cut‐off value was 8.5. Multivariate stepwise logistic regression showed that while QSPT failed to establish any suitable modeling, mQSPT and cube copy were related to the distinction between the two diseases. Moreover, the efficacy of these two indexes to distinguish AD and DLB: the sensitivity was 70.5%, and the specificity was 84.1% and the area under the ROC curve was 0.817(95%CI: 0.743‐0.891).ConclusionThe mQSPT can be used for the screening tool in differential diagnosis between AD and DLB patients.

Open RoAD: Design and baseline characteristics of an open‐label rollover study evaluating long‐term safety and tolerability of subcutaneous gantenerumab in participants with early Alzheimer’s disease

AbstractBackgroundGantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). SCarlet RoAD (SR) (NCT01224106) and Marguerite RoAD (MR) (NCT02051608) were two Phase III trials which assessed the efficacy and safety of subcutaneous (SC), low‐dose gantenerumab in participants with prodromal and mild AD, respectively, for up to 2 years. Following a gap period gantenerumab treatment was continued with uptitration to a dose of 1,200 mg monthly in open‐label extensions (OLE), which demonstrated substantial Abeta removal by positron emission tomography without new or unexpected safety findings. Here, we describe the study design, present baseline characteristics, and safety data from an additional open‐label, multicenter, rollover study, Open RoAD (OR) (NCT04339413), collecting long‐term safety and tolerability data for gantenerumab in participants who completed the SR OLE or MR OLE.MethodParticipants who completed either OLE study and were treated with doses up to 1,200 mg of gantenerumab for up to 5 years continue to receive the same dose of SC gantenerumab (every 4 weeks [q4w]) for 2 additional years in OR. The primary objective is to evaluate long‐term safety and tolerability by assessing adverse events, including amyloid‐related imaging abnormalities, and injection‐site reactions. Exploratory efficacy objectives include Mini‐Mental State Examination (MMSE) total score. The long‐term effect of gantenerumab on pharmacodynamic measures and biomarkers will also be explored.Result Baseline characteristics Fifty‐nine participants from SR OLE and 56 participants from MR OLE received at least one dose of gantenerumab in OR. The median participant age at baseline was 78 years, and the majority of the participants were female (61%). Sixty‐seven percent of participants were apolipoprotein‐E‐e4 (APOE e4) carriers. The median total MMSE score at baseline was 16. Safety data will be presented. ConclusionThe RoAD studies are among the longest‐duration OLEs of an anti‐amyloid monoclonal antibody. Data from the OR study demonstrate that gantenerumab at doses of 1,200 mg administered SC q4w is well tolerated, with no new or unexpected safety findings in patients with early AD.

Peripheral transport proteins were associated with 4‐year cognitive decline in APOE ε4 non‐carriers: A longitudinal, population‐based study

AbstractBackgroundSoluble low‐density lipoprotein receptor‐related protein‐1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid‐β (Aβ).We aim to determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association.MethodCognitively normal subjects were followed‐up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini‐Mental State Examination (MMSE), and cognitive decline was defined as a ≥2‐point decrease of MMSE after 4‐years. The association between baseline sLRP1/sRAGE and 4‐year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship.Result769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4‐year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13‐3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ε4 non‐carriers (adjusted OR = 1.60, 95% CI: 1.04‐2.48, p = 0.034).ConclusionIndividuals with lower levels of sRAGE had an increased risk of 4‐year cognitive decline in APOE ε4 non‐carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.

The combined effect of β ‐amyloid and white matter hyperintensities on present and future executive function performance in cognitively normal older adults

AbstractBackgroundβ‐amyloid (Aβ) and White matter hyperintensities (WMH) are key drivers of cognitive decline in healthy older adults and both are considered biomarkers of preclinical dementia. Deficit in executive function (EF) linked to WMHs and Aβ burden, have been shown to predict the development of dementia. The present study aimed to explore the interactions of regional and global Aβ with WMH on baseline and longitudinal performance in EF in cognitively normal (CN) older adults.MethodGlobal and regional Standard Uptake Value ratios (SUVr) from Aβ‐PET, WMH volumes from MRI FLAIR images, and composite scores of EF at baseline and after approximately 2 years were analyzed across a sample of 714 clinically‐normal (Mini‐Mental State Examination (MMSE) ≥ 26), aged participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI2). We used multiple regression models including the interaction tem and main effects for Aβ and WMH to investigate the independent and combined associations of these pathologies with EF. Age, ApoE, education, baseline EF score, and time to follow up EF testing were entered as covariates in the regression models.ResultThe moderation regression analysis showed that additive effects on Aβ burden and WMH in relation to baseline EF with p value for the interaction term between the two pathologies 0.07, and significant interaction effects of global, frontal and cingulate Aβ burden, and WMH in relation to longitudinal EF performance with p values of 0.037, 0.03, and 0.032 respectively. The main effect from regression analysis demonstrated that baseline EF performance was predicted by the combination of Aβ burden and WMH, while Aβ burden was the only predictor for longitudinal EF performance.ConclusionThese data demonstrated that baseline Aβ and WMHs have both independent effects on EF scores at baseline and synergistic effects on longitudinal EF performance. The biological relationships and interplay between Ab and WMH responsible for the synergistic effects seen on longitudinal EF performance warrants further study.

Plasma lipid signature as an indicator of the risk and rate of progression from mild cognitive impairment to Alzheimer’s disease

AbstractBackgroundOur knowledge about the importance of lipids in progression and the rate of progression from Mild Cognitive Impairment (MCI) to AD is limited. Our objective was to determine plasma lipids that could be implicated in the progression or rate of progression from MCI to AD.MethodWe analyzed the plasma lipid profile of MCI patients (N = 90) by liquid chromatography coupled with mass spectrometry. The association of lipids with progression was studied by logistic regression and a Cox regression model was used to assess lipids associated with the speed of progression. We adjusted our analyses for age, sex, CSF core AD biomarkers, APOE4 status, and Mini‐Mental State Examination (MMSE).ResultForty‐seven (52%) MCI patients progressed to AD during follow‐up (58 ± 12.5 months). Regression analysis detected that presence of APOE4 allele and high levels of four lipids – two as risk factors (p = 0.002) and two as protectors (p = 0.002 and p = 0.003)– were associated with progression (AUC 0.972, p < 0.001). The effect of these lipids in separating progressive from non‐progressive patients was significant when compared with the regression model without them (AUC 0.729 vs 0.972, z = 4.595, |z|>2.575, p < 0.01). Seven lipids were associated with the rate of progression, of which two were associated with a shorter time to progression (OR 9.88, 99% CI [3.08 –31.71], p < 0.001 and OR 34.81, CI 99% [4.88 – 248.3], p < 0.001) and five with a longer time to progression (OR 0.34, 99% CI [0.135 – 0.870], p = 0.003; OR 0.164, CI 99% [0.056 – 0.479], p < 0.001; OR 0.153, 99% CI [0.056 – 0.419], p < 0.001; OR 0.148, CI 99% [0.034 – 0.644], p = 0.001; and OR 0.029, 99% CI [0.007 – 0.131], p < 0.001).ConclusionOur results suggest that lipid dysregulation could have an important role in progression and rate of progression from MCI to AD. Our data also indicate that AD lipid alterations could have clinical implications as circulating biomarkers of progression and progression speed.

Feasibility of a remote dance intervention for institutionalized older people with cognitive impairment

AbstractBackgroundDance therapy has recently been proposed as a non‐pharmaceutical strategy to improve cognitive decline in people with Dementia or MCI, as well as to improve certain psychosocial aspects such as quality of life, mood and functionality. Due to the COVID‐19 pandemic, most older people living in long‐term care institutions have had their activities of daily living – such as physical therapy and other activity groups – interrupted to preserve social distancing rules. Therefore, the aim of this study was to create a dance therapy program that could be implemented as a remote intervention for older people living in a long‐term institution who had Mild Cognitive Decline (MCI) or Dementia.MethodA selection of older people, living in a long‐term institution in the city of Juiz de Fora, Brazil, diagnosed with MCI and Dementia, was made. To achieve this objective, the medical records of the residents were analyzed and screening tests such as the Mini‐Mental State Examination (MMSE) and, as a secondary measure, the Geriatric Depression Scale (GDS) were applied.ResultAfter the screening process, the program was planned with the help of a certified Senior Dance instructor, in order to arrange choreographies that were safe for all participants and could be performed remotely. In total, the program had 29 sessions, which spanned a period of 15 weeks, twice a week. There was an intervention group consisting of five participants with MCI or Dementia. A social worker of the institution helped with the choreography, in person, and a group of seven undergraduate students from different backgrounds (psychology, medicine and music) took turns conducting the remote sessions.ConclusionThe remote program was extremely well received by its participants and by the caregivers of the institution: they reported that the participants were waiting for the sessions and that their disposition and mood improved significantly since the beginning of the intervention. This allowed us to conclude that the creation of a remote dance program was not only feasible, but that it can promote mental and cognitive health in institutionalized older people with cognitive impairment. Thus, this strategy should be better explored by these institutions.

Correlation between depression, loneliness, challenging behavior and MRI findings among persons with high‐risk for cognitive impairment (PWHRCIs)

AbstractBackgroundthis study explored the relationships between depression, loneliness, challenging behaviors among persons with high‐risk for cognitive impairment (PWHRCIs). MRI findings were collected as well.MethodThis was a secondary analysis of a cross‐sectional study. Primary data were collected from the mother project “ Social Cognition, Nutrition and Cognitive Function in Middle Life: A Longitudinal Study ” (MOST‐107‐2314‐B‐182076) between 2018 to 08/14/2021. 176 participants were recruited, among which 24 participants had received MRI examination. Test battery included: Taiwanese version of Frontal Behavioral Inventory (TFBI) for challenging behaviors, the Geriatric Depression Scale Short Form (GDS‐SF) for depressive symptoms, the short‐form UCLA Loneliness scale (ULS‐8) for loneliness, the Mini‐Mental State Examination (MMSE) for global cognition, while MRI indicators included T1‐weighted image (T1W1), Resting‐state functional MRI (RS‐fMRI) and Diffusion Weighted Image (DWI).Resulthierarchical regression model results show: Model I, depressive symptoms predicted challenging behavior, explaining 12% of variance (R2 = .12). Model II, loneliness was added and significantly predicted challenging behavior with an 8% of increased variance. In total, Model II explained 20% of variance. Therefore, loneliness is a mediator between depressive symptoms and challenging behavior. 2. Loneliness was significantly correlated with the Brain Structural Networks (normalized characteristic path length) (r = ‐.47*, p<.05). 3. Challenging behavior was significantly correlated with the Brain Structural Networks (normalized characteristic clustering coefficient and normalized characteristic path length) (r = .78, p<.01; r = .83, p<.01, respectively). 4. Challenging behavior was significantly correlated with the Brain Functional Networks (Small‐world index and normalized characteristic clustering coefficient) (r = ‐.57, p<.05; r = ‐.49, p<.05, respectively), while the network indicator was thought to be random.ConclusionThe results indicated that depression and loneliness an affect challenging behavior in PWHRCIs. The results of MRI findings also highlight the importance of loneliness which may slow down the structural connections in the brain to transmit messages. Challenging behavior is also associated with functional brain connectivity. Therefore, it is necessary to regularly assess the emotional factors of PWHRCIs and provide individualized care to avoid further damage to their brain.

Association between APOε4 allele and cognitive function in healthy Brazilians elderly from Baixada Santista

AbstractBackgroundThe faster memory decline was associated with the presence of the apolipoprotein E4 (APOε4) allele, a genetic risk factor for late‐onset Alzheimer’s disease (AD). Studies suggest that the relationship between cognitive decline and APOE ε4 allele in healthy elderly may reflect the preclinical risk to AD. This study examined the influence of apolipoprotein E4 (APOε4) genotype on the cognitive function of the older people from Baixada Santista (Brazil).MethodThis study was approved by the Ethical Committee Board from Medical School/UNIMES (Number: CAAE 20938619.4.0000.5509). Seventy‐two participants with ≥65 years old, both sexes. were eligible for the study. Cognitive function and the level of physical activity were assessed by the mini‐mental state examination (MMSE) and Baecke questionnaire for older, respectively. APOE genotyping was performed in 66 out of the 72 participants. Statistical analysis was performed by using the BioEstat version 5.0, Kolmogorov‐Smirnov test, z‐score, student t or Mann‐Whitney test was applied according to the normality. The Chi‐square test was used for comparison between the sexes. Pearson correlation was also performed. P < 0.05 was considered statistically significant.ResultsSeventy‐two older people were assessed (women = 52 and men = 20), and the mean age was 73±7 years old, Baecke score (3.74 ±3.82), MMSE (27±3), and educational status (8 ± 4 years). As expected, a positive correlation was detected between the education level and MMSE score (r = 0.359, p < 0.05). No difference was found between the sexes for age, level of physical activity, MMSE, and education status (p > 0.05). Regarding the APOE genotype, we found the following frequency ɛ2/ɛ2 (1.5%), ɛ2/ɛ3 (16.7%), ɛ2/ɛ4 (1.5%), ɛ3/ ɛ3 (59.1%), and ɛ3/ɛ4 (21.2%). No correlation was found between carriers (presence of the ɛ4 allele) and non‐carrier for the MMSE score, varying between 27 to 30.ConclusionOur preliminary data show that the less educational status influences the cognitive decline in the older Brazilian population. However, no differences between the sexes were observed for all parameters indicating a homogenous population. Additionally, the cognitive function score was not influenced by the presence of the APOɛ4 allele in this population.

The Endophenotypic Effect of the SORL1 Variant rs2298813 on Regional Brain Volume in Patients with Alzheimer’s Disease

AbstractBackgroundTwo common variants of sortilin‐related receptor 1 gene (SORL1), rs2298813 and rs1784933, have been associated with late‐onset Alzheimer’s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two SORL1 variants remain unknown. We aimed to determine whether the two SORL1 polymorphisms were associated with any volumetric differences in brain regions in AD patients.MethodsWe recruited 200 patients with late‐onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini‐Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.ResultThe rs2298813 and rs1783933 genotypes were not associated with cognitive test performance or clinical progression. The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (p = 0.0442) and right pallidum (p = 0.0346). There was no link of the rs1784933 genotypes with any of the imaging measures. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (p = 0.008) and clinical progression (p = 0.020). In the minor allele carriers, the right putaminal and right pallidal volumes were not significantly related to cognitive test scores or clinical progression.ConclusionThe major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function.

Cognitive function and its influencing factors in chinese with advanced age: An observational study based on comprehensive geriatric assessment

AbstractBackgroundCognitive impairment is an age‐related clinical problem that has a significant negative impact on the quality of life of elderly individuals. Hence, it is necessary to identify and intervene the factors affecting cognitive impairment early. Comprehensive geriatric assessment (CGA) is a multidimensional, multidisciplinary diagnostic and therapeutic process used to evaluated the medical, psychosocial, and functional abilities of older adults. This study aimed to evaluated the cognitive function and to explored the risk factors in the old elderly in Chongqing, southwest China by analyzing the CGA assessment data.MethodA cross‐sectional study was conducted in 551 inpatients aged 80 years or older of Department of Geriatrics in The First Affiliated Hospital of Chongqing Medical University from July 2017 to August 2018. Participants were measured with CGA to assess the physical condition, cognition, mental health status, fatigue, nutrition, and presence of geriatric syndromes. Cognitive function was assessed with the Mini‐Mental State Examination (MMSE). The factors associated with cognitive function were analyzed with independent sample t‐test, chi‐square test, and rank‐sum test. The relationship between cognitive impairment and risk factors was examined with logistic regression analysis.ResultAmong the 551 subjects, 313 (56.8%) had different degrees of cognitive impairment. The cognition function was obviously correlated with literacy (z = ‐3.294,P< 0.001), diabetes (x² = 6.862,P< 0.009), nutrition (z = ‐3.466, P<0.001), GDS‐5 (x² = 25.955, P<0.000). Furthermore, logistic regression analysis showed that age (odds ratio (OR) = 1.117, 95% confidence interval (CI): 1.1048–1.190), no diabetes (OR = 0.628, 95% CI:0.400–0.984), normal GDS‐5 (OR = 2.417, 95%CI: 1.568–3.000), and malnourished (OR = 2.481, 95%CI:1.159–5.313) were significantly associated with cognitive function.ConclusionOur results suggest that age, poor literacy, diabetes, depression and malnutrition are significantly associated with an increased risk of cognitive impairment. Therefore, improving nutritional status, controlling blood glucose and regulating emotions have positive regulatory effects on cognitive function of the older elderly.

Cognitive function level and chronic disease incidence rate by age of older adults living in the community

AbstractBackgroundResearch has shown that decline in cognitive function is related to the level of chronic disease in old age. Most studies, however, have either examined limited aspects of cognitive function or used assessment tools with low accuracy. A limited range of cognitive function items and low‐accuracy cognitive function assessment tools may bias the findings. Current literature also has paid little attention to the age‐gradient association between cognitive function and chronic diseases. Utilizing a new cognitive classification method, this study investigated cognitive function‐associated chronic diseases and their relationship with age. Empirical knowledge about the dynamic among cognitive function, changes in chronic diseases, and age may contribute to establishing comprehensive prevention and management programs of diseases in later years.MethodA total of 6,940 people aged between 55 to 105 years from the 2018 Korean Longitudinal Study of Aging panel data were included in this study. According to the Korean Mini‐Mental State Examination’s total score and instrumental activities of daily living assistance, cognitive status was classified into normal cognition, moderate cognitive impairment, and severe cognitive impairment. The Poisson regression analysis was used to calculate the incident rate ratios (IRR) of cognitive status by age and the incidence of chronic diseases.ResultThe incidence rate of chronic diseases was 1.07 times higher in the moderate cognitive impairment group (n = 4665) than in the normal cognitive group (n = 4665). In addition, it was 1.24 times higher in the severe cognitive impairment group (n = 420) than in the normal cognitive group (Table 1) and the incidence of chronic diseases according to cognitive function increased with age (figure 1).ConclusionApplying the new cognitive function classification, we found the incidence rate of age‐related chronic diseases increased with the cognitive status, indicating incidence of chronic diseases increases as the cognitive state decreases and the age increases, leading to complex chronic conditions. This finding points to the importance of an integrated program of cognitive decline prevention and the chronic disease management program, which are currently developed and implanted separately.