bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep sleep predicts the cognitive evolution of mild‐moderate Alzheimer’s disease patients
Authors: Targa Adriano , Benitez Ivan David , Dakterzada Faride , Minguez Olga , Barbe Ferran , Piñol‐Ripoll Gerard
Published: December 2021

Background

To investigate the association between sleep and the cognitive evolution of mild‐moderate Alzheimer’s disease patients.

Method

Observational, prospective, single‐center study, including consecutive patients diagnosed with mild‐moderate Alzheimer’s disease (NCT02814045). The individuals were submitted to overnight polysomnography, followed by neuropsychological evaluations at baseline and after 12 months of follow‐up. Principal component analysis characterized the sleep architecture of the cohort into two main types: individuals with a propensity to deepen their sleep (deep sleepers) and individuals who spent most of the time in the lighter sleep stage (light sleepers).

Result

The cohort included 125 subjects with a median [IQR] of 75.0 [72.0;80.0] years. The mean difference (95% CI) in the Mini‐mental state examination score at 12 months between deep and light sleepers was ‐1.51 (95% CI: ‐2.47 to ‐0.54; p‐value = 0.002). Accordingly, sleep depth and cognitive evolution presented a dose‐response relationship (p‐for‐trend = 0.02). Regarding the specific cognitive subdomains, we observed differences related to the processing speed, demonstrated by the Stroop words test (‐1.48; 95% CI: ‐2.58 to ‐0.38; p‐value = 0.009), and to the executive function, demonstrated by the Verbal fluency test (‐1.70; 95% CI: ‐2.85 to ‐0.55; p‐value = 0.004).

Conclusion

Considering that light sleepers presented an increased cognitive decline, the sleep profile may have a predictive role in the cognitive evolution of mild‐moderate Alzheimer’s disease patients. The modifiable nature of sleep sets this behavior as a possible useful intervention for the improvement of cognitive evolution.
Empirically derived composite cognitive test scores to predict preclinical and clinical stages of Alzheimer’s disease
Authors: Shishegar Rosita , Chai Tze Young , Cox Timothy , Lamb Fiona , Robertson Joanne S. , Laws Simon M. , Porter Tenielle , Fripp Jurgen , Doecke James D. , Tosun‐Turgut Duygy , Maruff Paul T. , Savage Greg , Rowe Christopher C. , Masters Colin L. , Weiner Mike W. , Villemagne Victor L.L. , Burnham Samantha C.
Published: December 2021

Background

Alzheimer’s disease (AD) clinical trials require cognitive test scores that assess change in cognitive function accurately. Here, we propose new composite cognitive test scores to detect earlier stages of AD accurately by using the full neuropsychological testing battery (in ADNI) and a manifold learning dimension reduction technique namely UMAP.

Method

Data for this study included N=1585 ADNI participants ([492 cognitively normal (CN), 804 mild cognitively impaired (MCI), 289 AD; aged 73.8±7.1; 708 females]; Table 1). Subjects with 3 or more follow‐up sessions were included. Cognitive test scores with more than 60% missing data were excluded. Missing data within included test scores were imputed using the MissForest algorithm. A linear mixed model using all follow‐up data was applied to calculate the random slope (rate of change) and random intercept for each cognitive score and for each subject. The scores and demographic measurements: age, gender, years of education and APOE‐ɛ4 status were used to inform the UMAP. Levels for the output variable were defined as: 1) stable CN, 2) CN who progressed to MCI or probable dementia due to AD, 3) stable MCI, 4) MCI who progressed to dementia AD and 5) dementia due to AD. The model calculated two composite scores. These cognitive stages were predicted using Support Vector Machine (SVM) analysis of both the new composite scores and the traditional clinical rating measures of Clinical Dementia Rating (CDR) and Mini‐Mental State Examination (MMSE).

Result

Predicting cognitive stages using the proposed composite scores show a highly significant improvement with a 0.981 accuracy and 0.976 reliability (evaluated by Cohen's kappa coefficient), compared to using the combination of CDR and MMSE scores covaried for demographics, which had 0.660 accuracy and 0.567 reliability. Individuals’ clinical and preclinical stages with regards to UMAP two‐dimensional embedding and the clinical rating measures, CDR and MMSE, are presented in Figure 1. Table 2 reports the importance of the test measures on the UMAP components used in AD staging predictions.

Conclusion

The results here suggest that the proposed empirically derived composite cognitive test scores provides a practical solution to differentiate cognitive stages with a high accuracy and reliability.
The brain correlates of behavioral disturbances in frontotemporal dementia
Authors: Fiondella Luigi , Mattioli Irene , Salemme Simone , Carbone Chiara , Vinceti Giulia , Tondelli Manuela , Chiari Annalisa , Molinari Maria Angela , Huey Edward D. , Jenkinson Mark , Grafman Jordan , Zamboni Giovanna
Published: December 2021

Background

Various studies have researched singular or clusters of behaviors in frontotemporal dementia (FTD) correlating them with regional brain atrophy in structural MRI data, or hypometabolism in FDG‐PET images, but a multimodal approach is lacking. We identify the brain correlates of modes of variation (i.e., factors) explaining the variability of behavioral and psychological symptoms (BPSD) in frontotemporal dementia (FTD) using multimodal imaging.

Method

Imaging and behavioral data from 93 FTD patients acquired at NIH were analyzed. They underwent extended neuropsychological assessment including several scales measuring BPSD (UCLA NPI, FrSBe, and Neurobehavioral rating scale), T1‐weighted MRI, and FDG‐PET imaging. Factor analysis was used on the behavioral data to identify modes of variation of BPSD potentially pointing to few common neurobiological substrates across the FTD sample. The identified modes were then related to intersubject brain variability using a newly developed fusion method run on maps of gray matter volume and FDG metabolism obtained.

Result

A factor related to decreased emotional/cognitive interaction (loading scores of apathy, executive dysfunction, withdrawal) correlated with volume and function of the right anterior cingulate and orbito‐frontal cortex. A factor expressing variability on mutacism versus disinhibition/euphoria continuum was associated with dysfunction of the right superior primary motor cortex. A factor related to the presence of hallucinations/delusions/suspiciousness was associated with dysfunction of the right anterior insula.

Conclusion

BPSD variability in patients with FTD can be explained by 3 major modes of variations, each associated with intersubject brain structure/function variability of the right frontal lobe.
Analysis of cognitive and functional states with relation to variables: A quantitative study in Mauritius
Authors: Dorkhy Geeta Devi
Published: December 2021

Background

To identify the relationship between factors that accelerate cognitive or functional decline in person with Alzheimer's disease

Method

Quantitative method, using pre‐validated MMSE questionnaire and Katz Index of Independence in ADL along with demographical data. Using SPSS and Chi‐square test to obtain p‐values and statistical relations and significance between these associations in table forms.

Result

Normal cognitive function was noted in 53.7% of total sample (n=42) while normal functional states was 73.8% in same sampled population. Severe cognitive decline accounted for 26.8% and severe functional impairment was 11.9%.

Conclusion

All the p‐values exceed 0.05, in association between MMSE and associated variables (gender, age, occupation, medical illness, marital status, family status, smoking and drinking habits). MMSE is not significantly associated with any of the variables at 5% level. Neither gender nor occupational status had any significant bearing on ADL at 5% level.
Changes in the awareness of cognitive decline across the course of Alzheimer’s disease: Comparison of two assessment methods
Authors: Cacciamani Federica , Valladier Arnaud , Maheux Etienne , Koval Igor , Durrleman Stanley , Epelbaum Stéphane
Published: December 2021

Background

Recent studies have suggested that poor awareness of cognitive decline (ACD) could be an early indicator of Alzheimer's disease (AD). However, there is still no gold‐standard for ACD assessment. In this study, we describe longitudinal changes in ACD in subjects with biomarker‐defined AD (according to the A/T/N framework by Jack and colleagues), assessing ACD by two methods: a subject‐informant discrepancy and a subjective‐objective scores discrepancy.

Method

We included 334 amyloid‐ and tau‐positive (A+T+) subjects with normal cognition, MCI and dementia, and 137 cognitively‐normal A‐T‐ controls from the ADNI cohort, followed up for an average of 5 years. Using a statistical mixed‐effects model (Couronné & al., 2019, ISBI), we reconstructed the evolution of a composite memory score, self and informant’s assessments of cognitive functioning (E‐Cog) and two ACD measures: the ACD index (ACDI, i.e. the difference between E‐Cog‐Subject and E‐Cog‐Informant) and the Meta‐Memory Ratio (MMR, Gagliardi et al. 2019 ART, i.e. the comparison between the E‐Cog‐Subject and a composite memory score). After rescaling the scores, an abnormality threshold was calculated for each of them corresponding to the 95th percentile of the distribution of control subjects.

Result

The subject perceives, at the beginning of the disease, a cognitive decline that is not detected neither by the informant (Figure 1) nor by the tests (Figure 2). This condition can be called "hypernosognosia". The subjective cognitive decline increased slightly and became abnormal 2 years after the diagnosis of dementia. A clear anosognosia was visible starting from the MCI phase using both assessment methods. The MMR detected a reduction in ACD earlier than the ACDI: the subject passes from a hypernosognosia to a good match with the memory score between 64 and 69 years, and with the informant rating between 73 and 76 years on average.

Conclusion

Hypernosognosia is associated with a risk of AD during a short period of time, when the disease is at a very early stage. Thereafter, the individual's ACD decreases. We will discuss the advantages and disadvantages of both assessment methods in both research and clinical practice, especially in relation to their usefulness for early detection of AD.
The risks of polypharmacy in ambulatory and home care patients affected with dementia: The PharE Study
Authors: Gareri Pietro , Russo Emilio , Condito Andrea , De Sarro Giovambattista
Published: December 2021

Background

Older patients affected with comorbidities often take a lot of potentially inappropriate drugs. This can cause side effects, hospitalization and even death.

Aim

The aim of the present study was to assess dangerous drug interactions and potentially inappropriate drugs administered to a sample of ambulatory and home care patients affected with dementia.

Methods

41 ambulatory outpatients and 53 home care patients affected with dementia were selected randomly between January 1st 2017 and December 31st 2019. They were visited at the Center for Cognitive Disorders and Dementia, Catanzaro Lido, Italy.

Personal, clinical data and drugs taken were collected; comorbidities were assessed through CIRS, ADL, IADL, MMSE. Beers criteria were used in order to assess the potentially inappropriate drugs.

Results

Of 100 patients, 64 were women and 36 men, mean age 83,7 ± 4,9 and 82,1 years old ± 11,8 years old respectively. 50% of them were affected with mixed dementia, 13% Alzheimer’s dementia, 9% Parkinsonism, 10% depression with associated cognitive impairment, 18% dementia of other kind. Mean MMSE score was 15,99 ± 8,84. Each patient was taking 9,17 ± 3,31 drugs on the average, 56% of them 5‐9 drugs and 39% 10 drugs or more. 66% of patients was taking one inappropriate drugs or more, proton pump inhibitors (PPI) (51%), atypical and conventional antipsychotics (23% and 6% respectively), benzodiazepines, amiodarone, calcium antagonists (3%), tricyclic antidepressants and a‐blockers (2%), old generation anti‐histamine drugs (1%). 56% of them were taking a drug with anticholinergic properties.

Conclusions

The study shows a high percentage of drugs with anticholinergic properties, which can increase the risk for dementia or even worsen cognitive impairment. Furthermore, inappropriate drugs were stopped and changed with more tolerated compounds. PPI use was dramatically reduced. The study suggests the need for a careful check of treatment in every patient, and for personalizing treatment in older patients with dementia. A larger sample could bring more information to healthcare providers as well as the use of softwares for helping doctors to limit the risk for drug interactions.
Comparison of white matter hyperintensity abnormalities and cognitive performance in individuals with low and high cardiovascular risk: Data from the Diabetes and Dementia (D2) study
Authors: Restrepo Carolina , Patel Sheila , Khlif Mohamed Salah , Bird Laura J. , Singleton Rebecca , Yiu Chi Him Kendrick , Werden Emilio , Ekinci Elif , MacIsaac Richard , Burrell Louise , Brodtmann Amy
Published: December 2021

Background

Type 2 diabetes Mellitus (T2DM) is recognised as a major contributor to cognitive decline. People with T2DM demonstrate increased white matter hyperintensity (WMH) abnormalities on MRI compared to control individuals. We investigated associations between a validated vascular risk score: The Framingham Risk Score (FRS), WMH volumes and cognitive function in the Diabetes‐and‐Dementia (D2) study, a longitudinal cohort study of community dwelling people with T2DM.

Method

One hundred and twenty‐three non‐demented participants with T2DM (age 66.7±6.8 years, range 50‐80, 68M/55F) completed neuropsychological assessments, health questionnaires to allow FRS calculation, 24‐hour ambulatory blood pressure monitoring, and a 3T‐MRI scan. WMH were calculated using the functionality "run‐samseg" in FreeSurfer 7. Quality control on the traced lesions was performed using an in‐house semi‐automated MATLAB tool. Periventricular and deep WMH volumes were estimated based on the edited lesion traces. We divided participants into low (n=61) and high (n=62) FRS groups based on the median score (x=48.7). Differences in WMH volumes were compared between the FRS groups after correcting for sex and age. We compared cognitive performance between low/high FRS individuals across five composite cognitive domains: memory, language, visuospatial skills, executive function, and attention‐and‐processing‐speed. The composite score for each domain was the normalised z‐scores average for the respective tests.

Result

Participants with high FRS (implicating greater vascular risk) were significantly older (age F(1, 122)=14.97; p<0.001), were less likely to be female (sex χ2=16.73, p<0.001), and tend to have less than 12 years of education (χ2= 3.69, p = 0.041). Relative to individuals with low FRS, those with high FRS showed significantly higher WMH volumes (F(1, 121)=6.11; p=0.015). Significant differences were also identified for periventricular (F(1, 121)=6.16; p=0.014) and deep (F(1, 121)=4.25; p=0.042) WMH volumes. When the cognitive data were analysed, the low FRS group performed signifcantly better than the high FRS group only on the attention‐and‐processing‐speed factor (F(1,115)=5.17; p=0.025).

Conclusion

High cardiovascular risk, defined as a high FRS, in participants with T2DM was associated with greater WMH volume, a marker of white matter dysfunction, and with deficits in processing speed and attention. Subclinical cognitive deficits were common in our community dwelling cohort without known or preceding cognitive dysfunction.
A novel method for tracking the progression of WMHs through the alignment of premortem in‐vivo to postmortem ex‐vivo MRI and histopathology
Authors: Schweitzer Noah , Farhat Nadim , Wu Minjie , Kofler Julia , Berardinelli Jacob , Ibrahim Tamer , Iordanova Bistra , Aizenstein Howard J
Published: December 2021

Background

White matter hyperintensities (WMHs) are neuroimaging features associated with Alzheimer’s disease (AD). Ex‐vivo studies may enable better characterization of WMHs pathological substrates. In this work, we present a novel method that leverages in‐vivo and ex‐vivo MRIs and histopathology to analyze the progression of WMHs in AD.

Method

A single subject’s in‐vivo MRI scans at four different time points were analyzed. Ex‐vivo scans of the brain left hemisphere were done using 16‐Tx and 32‐Rx TicTacToe coil3 and a 3‐D printed enclosure with integrated cutting guides1 (Fig. 1). The WMHs were segmented on the T2‐weighted FLAIR in‐vivo MRI 2, and registered onto the final time point via SPM’s normalized mutual information‐based algorithm. All four WMH segmentations were warped to the ex‐vivo MRI’s space by applying the deformation field from the ITK in‐vivo to ex‐vivo registration.

Result

The 3D printed enclosure achieved an accurate alignment between gross pathology, ex‐vivo and in‐vivo MRI (Fig. 1). Then, we computed the WMHs’ growth over time warped onto the ex‐vivo MRI (Fig. 2). This growth was quantified as the total number of voxels in each segmentation longitudinally with a quadratic fit with an R2 =0.99 (Fig. 2). Lastly, we found a significant change in the distribution of WMH segmentations over time as evident by their normalized histograms (Fig. 3).

Conclusion

We present a novel method to track the progression of WMHs in‐vivo to ex‐vivo MRI and gross pathology. Future studies will perform a voxel‐wise analysis on the WMHs in MRI scans, both in‐vivo and ex‐vivo, along with its histological correlates to gain insight into the underlying cellular mechanisms during the biomarker’s development. References: 1. Nadim Farhat et al. “Reusable 3D printed enclosure with integrated cutting guides for the alignment of high resolution ex‐vivo MRI with ex‐vivo gross brain photographs.” 2021 ISMRM Meeting (Under revision). 2. Wu, M. et al (2006). “A fully automated method for quantifying and localizing white matter hyperintensities on MR images.” Psychiatry Research: Neuroimaging, 148(2‐3), 133‐142. 3. T. Santini et al., “In‐vivo and numerical analysis of the eigenmodes produced by a multi‐level Tic‐Tac‐Toe head transmit array for 7 Tesla MRI,” PLoS One, vol. 13, no. 11, p. e0206127, Nov. 2018.
Daily coffee intake in midlife and enhanced late life cognition in twins
Authors: Chanti‐Ketterl Marianne , Johnson Kim , Plassman Brenda L
Published: December 2021

Background

Coffee drinking has shown mixed results in its association with cognitive function in later life, likely due in part to influence from unmeasured genetic and environmental factors, leading to inconsistent findings between studies. Given that members of twin pairs share at least some of their genes and many early‐life experiences, twin studies have advantages in providing control for confounding factors, many unidentified, that affect late‐life cognition. We aimed to explore if coffee intake in midlife maintains cognitive function in late‐life.

Method

A total of 7,438 members of the NAS‐NRC Twin Registry of Male World War II Veterans born from 1917–1927 were included in this study. Number of cups of coffee consumed daily was collected via mailed questionnaire in 1967. Cognitive status was measured every 3 years from 1990‐2002 using the modified Telephone Interview for Cognitive Status (TICS‐m) (range 0‐50). Daily coffee intake was categorized as tertiles (T):(T1)=1‐2 cups, (T2)=3‐4 cups, (T3)>5 cups, with reference=0 cups. Linear‐mixed‐effect regression models, controlling for age at time of initial TICS‐m, education, smoking and alcohol status and twin pair, were used to assess the association between daily intake of coffee in midlife and performance on the TICS‐m over a period of up to 12 years in later life.

Result

Participants’ mean age was 41.7 years (standard deviation (SD)=2.8) when information on coffee intake was collected and 66.9(SD=2.8) at the time of their first TICS‐m. A total of 6,665 males reported drinking coffee, and the mean number of cups was 3.6(SD=2.4) daily. Twins who consumed more than 2 cups of coffee obtained higher TICS‐m scores (T2:b=0.53; 95%CI=0.22,0.85) and (T3:b=0.50;95%CI=0.18,0.82) than non‐coffee drinkers. This equates to an average of 2.4‐2.6 TICS‐m points more for those in T2 and T3 compared to non‐coffee drinkers. However, the amount of coffee intake was not associated with the rate of cognitive decline (T1:p=0.84,T2:p=0.28,T3:p=0.09).

Conclusion

We found that higher amounts of midlife coffee drinking are associated with better cognitive performance, but not reduced rate of cognitive decline in late‐life even after accounting for shared genetic and early‐life environmental factors. Future research should investigate potential mechanisms linking coffee and cognition.
Associations between sleep and Alzheimer’s disease biomarkers within the EPAD cohort
Authors: Naismith Sharon L. , Palmer Jake R. , Leng Yue , Lucey Brendan P.
Published: December 2021

Background

Changes in sleep quality are common in Alzheimer’s Disease (AD) and may even play a role in the onset and accumulation of disease. However, in preclinical stages, it is unclear whether sleep quality or sleep disturbance relate to disease pathology after controlling for known covariates and AD risk factors. This study aimed to determine if self‐reported sleep quality is associated with AD biomarkers after accounting for such factors.

Method

Data were obtained from the European Prevention of Alzheimer’s Disease (EPAD) Longitudinal Cohort Study (LCS) data set (v1500.0). Cerebrospinal fluid (CSF) samples were collected for measurement of b‐amyloid (Ab42) and phosphorylated tau (p‐tau). Self‐reported sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Participants with Clinical Dementia Rating (CDR) scale scores greater than 0.5, indicative of dementia, were excluded. Linear regression models were used to determine whether the p‐tau/Ab42 ratio was associated with PSQI component scores when controlling for multiple potential confounders such as demographics, ApoE4 status, depressive symptoms, body mass index, vascular risks, smoking status, use of psychotropics, white matter lesions, and hippocampal volume. PSQI component scores of 2 or 3 were combined due to small numbers of participants with component scores of 3.

Result

From the 1500 participants in the EPAD‐LCS v1500.0 data, a total of 1239 participants were included in the regression analysis (mean age=65.30 years, SD=7.11; mean PSQI total score=5.31, SD=3.38). After adjustment for all covariates, higher p‐tau/Ab42 ratio was found to be associated with longer self‐reported sleep latency (component score of 1: b=0.16, p=0.007; component score of 2/3: b=0.12, p=0.134; R2=0.22) and better self‐reported sleep efficiency (component score of 1: b=‐0.22, p=0.04; component score of 2/3: b=‐0.31, p=0.009; R2=0.22)

Conclusion

Within the EPAD cohort, longer sleep latency and greater efficiency are associated with greater AD pathology after controlling for covariates. These findings contribute to growing evidence suggesting sleep is an important early marker of underlying neurodegeneration. Longitudinal assessment of EPAD‐LCS participants will allow for the evaluation of self‐reported sleep as a predictive marker of neurodegeneration.
Preclinical amyloid‐PET SUVr in the precuneus and posterior cingulate associations with MoCA scores are driven by language domain subscores
Authors: Ali Doaa , Barber Justin M , El Khouli Riham H , Gold Brian T. , Harp Jordan , Van Eldik Linda J , Wilcock Donna M , Jicha Gregory A
Published: December 2021

Background

β‐amyloid (Aβ) deposition in the brain is the earliest pathological change supporting a diagnosis of preclinical Alzheimer’s disease (pAD). Such deposition can be quantified using amyloid‐PET scans, which also enable a quantitative evaluation of the distribution of the pathology in pAD. Cognitive screening instruments such as the Montreal Cognitive Assessment (MoCA) are widely used to detect cognitive decline as one transitions from pAD to mild cognitive impairment or dementia due to AD, but have little proven utility in tracking cognitive decline during the stage of pAD. The present study sought to identify potential relationships between regional Aβ deposition and domain specific subscales and items comprising the MoCA in pAD.

Method

Ninety‐nine clinically normal participants with a MoCA score ≥ 23 underwent F18‐florbetapir PET/CT scanning and regional standardized uptake value ratio (SUVr) was determined using the Siemens Syngo.via® Neurology software package. Relationships between regional SUVr and MoCA test performance as well as MoCA domain scores were analyzed using linear regression models adjusted for age and education.

Result

Subjects included 68 women and 31 men with a mean age of 74.2±6.3 years, education 16.7±2.6 years, and MoCA 26.6± 1.9. The adjusted linear regression analyses demonstrated that reduced global MoCA score was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p<0.05). This relationship appeared to be driven predominantly by the language domain index score rather than other subdomains of the MoCA (R2=0.122; p= 0.003).

Conclusion

These data demonstrate that increased Aβ deposition in the precuneus and posterior cingulate (the earliest brain regions affected with Aβ pathology) are associated with decreased global cognitive performance, driven by language domain subscores in individuals with pAD. Further research using more sensitive domain‐specific tests in cognitively normal individuals may help determine optimal low‐cost, non‐invasive, neuropsychological predictors of pAD.
Social health and reserve in the dementia patient journey (SHARED): The role of social interactions in the clinical phase of dementia
Authors: Samtani Suraj , Stevens Ashley , Lipnicki Darren M , Sachdev Perminder S , Brodaty Henry ,   SHARED Consortium
Published: December 2021

Background

The SHARED project is an international collaboration designed to investigate the role of social factors in the onset and course of dementia across the lifespan. We investigated the impact of social health on cognition throughout the clinical phase of dementia – an area that remains vastly under‐researched.

Method

We harmonised data from 12 international longitudinal studies of ageing (11 studies from the COSMIC consortium and the English Longitudinal Study of Ageing) to select participants who were had a diagnosis of mild cognitive impairment or dementia.

We investigated the impact of social factors on cognitive decline across 3 groups – those who had MCI and remained stable (n = 5706), those with MCI who declined into dementia (n = 659), and those who had dementia at baseline (n = 1236). A series of multi‐level, linear mixed models were run to determine the impact of social health factors, namely loneliness, social interactions, social activities, network size, living situation, social support and relationship satisfaction on the different trajectories.

Result

After controlling for age, sex, education, APOE e4 alleles, and physical health factors, significant differences emerged between the in the frequency of interactions. Specifically, the dementia at baseline group were less likely to engage in interactions monthly (β = ‐1.15, SE = .46, p = .01) or weekly (β = ‐1.08, SE = .42, p = .01) compared to the MCI stable group. No differences emerged in relation to network size, social support, or relationship satisfaction. Compared to the MCI decline group, the dementia at baseline group were more likely to be single (instead of married/in a relationship or separated/divorced), but this result did not emerge in studies which included APOE data.

Conclusion

Harmonised data from multiple longitudinal studies of ageing, demonstrated that people living with dementia were less likely to have frequent social interactions compared to people experiencing mild cognitive impairment. Further research is required to explore the trajectory of social interactions over time as individuals progress through the stages of dementia, and investigate the impact of cognitive and health factors on this trajectory.
Sex‐related differences in cognition with statin usage in a geriatric memory clinic cohort
Authors: Chan Alex K , Lo Tsz Wai Bentley , Karameh Wael K , Fornazzari Luis , Dadone Gianfranco , Golas Angela C , Barfett Joseph , Munoz David G. , Schweizer Tom A. , Fischer Corinne E.
Published: December 2021

Background

Recently, there has been debate for the suitability of statins for geriatric populations and patients with dementia as there is evidence suggesting improved quality of life following discontinuation of therapy in these groups, as well as conflicting evidence surrounding its potential to both prevent and potentiate downstream cognitive deficits. Despite large scale studies being conducted in the past regarding statins and cognition, there is a paucity of literature investigating its interaction with sex, as well as possible associations with other variables such as subjective complaints, neuropsychiatric symptoms, and function.

Methods

Analysis was done on patients assessed at a Memory Disorders Clinic at St. Michael’s Hospital between 2012 and 2017, comprising a population of 348 patients divided into groups taking daily atorvastatin (N = 45), rosuvastatin (N = 40), and controls (N = 263) (Table 1). Data form the Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Behavioural Neurology Assessment‐Revised (BNA‐R), Neuropsychological Impairment Scale (NIS), The Older Americans Resources and Services (OARS) Activities of Daily Living (ADL) Scale and Neuropsychiatric Inventory Questionnaire (NPI‐Q) were analyzed.

Results

Two‐way ANOVA demonstrated a significant interaction between sex, cognitive performance, and statin use in which female statin users scored significantly lower on multiple subdomains of the BNA‐R (p < 0.05) (Table 2). Patients taking atorvastatin additionally scored lower on CERAD delayed recall, delayed recognition, and in the cumulative recognition domain than other groups (p < 0.05). Atorvastatin and rosuvastatin were additionally associated with higher frequency of dysphoria and disinhibition, respectively (p < 0.05). No significant results were found in other measures investigated.

Conclusions

In addition to minor associations between atorvastatin usage and lower memory performance, findings from this investigation suggest a possible interaction between sex, cognition and statin use that has not been well documented in literature. Though these findings were not reflected in other measures such as subjective complaint or function, further research may be warranted to provide insight into the relationship between sex, statin usage and neurological effects.
The QuickSort: A brief cognitive screen to detect cognitive impairment in older adults
Authors: Foran Amie M , Mathias Jane L , Bowden Stephen C
Published: December 2021

Background

Sorting tests are amongst the most sensitive cognitive tests for detecting brain injury, but are rarely used to screen older adults for cognitive impairment. A recent meta‐analysis (Foran, Mathias & Bowden) found that sorting ability deteriorates in older adults who have been diagnosed with one of a number of common neurodegenerative disorders, suggesting that sorting tests may provide an alternative to cognitive screens. The QuickSort is a new test that improves on existing sorting tasks, with the manual and test stimuli freely accessible to users (Foran, Mathias & Bowden, 2020). It is quicker to administer and score, and better suited for use with older adults whose cognitive ability may be compromised.

Method

A consecutive cohort of older (≥60 years) community‐dwelling adults (n=187) and hospital inpatients who were referred for a neuropsychological assessment (n=73) were administered the Mini‐Mental Status Examination (MMSE), Frontal Assessment Battery (FAB) and QuickSort (9‐stimuli, which must be sorted by color, shape & number; Total score range = 0‐18; higher scores indicate better cognition). A Cognitively‐Healthy normative subsample (n=115), screened for cognitive and psychological disorders, was formed from the community sample.

Results

The Cognitively‐Healthy subsample completed the QuickSort within 2‐minutes, 50% had errorless performance, and 95% scored 10 or more. The likelihood of community‐dwelling older adults and inpatients (n=260) being impaired on either the MMSE or FAB, or both, increased by a factor of 3.52 for QuickSort Total scores <10 and reduced by a factor of 0.23 for scores ≥10.

Conclusion

Most healthy older adults complete the QuickSort quickly and easily. The QuickSort performance of a patient can be compared to their cognitively‐healthy peers in order to estimate the likelihood that they will be impaired on either the MMSE or FAB, or both. The QuickSort can also be customized for use in specific settings. The QuickSort may provide an alternative to lengthier cognitive screens (MMSE and FAB) in settings that have very limited clinical resources.
Applicability of deep neural networks and local binary pattern for the classification of MCI‐C and MCI‐NC
Authors: Bhasin Harsh , Deshwal Vishal
Published: December 2021

Background

The classification of Mild Cognitive Impairment (MCI) patients, who convert to Alzheimer’s (MCI‐C) and do not convert to Alzheimer’s (MCI‐NC) is important to understand the progression of the disease. The imaging data, particularly s‐MRI helps to understand the disease by capturing the variation in the gray matter.

Method

We developed a Deep Learning based method to classify MCI‐C and MCI‐NC. For each MRI volume Local Binary Pattern (LBP) was applied on each slice and the features so obtained were concatenated to get the feature vector of the volume. The features were obtained using three methods: creating a histogram having 256 bins, by using the Uniform LBP, and using the Uniform‐Rotation Invariant LBP. This feature set was fed to a Deep Neural Network having two hidden layers and a Softmax layer. Experiments were conducted to find the optimal architecture of the DNN, which gives the best accuracy. Also, a dropout layer was added to prevent overfitting. The results were also compared with the Support Vector Machine. The data used in the experiment was obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Result

We evaluated the model performance using accuracy. It was found that amongst the three variants of LBP, that having 256 bins produced the best results. Also, DNN performed far better as compared to SVM. Amongst the various DNN’s the one having 100 units in the first hidden layer, 50 in the next, and having a dropout of 0.1, gave the best results. The model used Adam optimizer and categorical cross‐entropy. It was also noted that the results obtained using raw volumes were inferior as compared to that obtained using LBP. Table 1 shows the results.

Conclusion

We propose a Deep Learning model for classifying MCI‐C and MCI‐NC. The proposed method is capable of finding discriminating features to classify the two sets. It may be the case that LBP is able to infer the difference in the distribution of microstructures in the two classes which helped the DNN to obtain better accuracy as compared to the state of the art.
Machine learning approaches to predicting amyloid status using data from an online research and recruitment registry: The Brain Health Registry
Authors: Albright Jack , Ashford Miriam T. , Jin Chengshi , Neuhaus John , Camacho Monica R. , Rabinovici Gil D. , Truran‐Sacrey Diana , Maruff Paul T , Mackin R. Scott , Nosheny Rachel L. , Weiner Mike W.
Published: December 2021

Background

This study investigated the extent to which subjective and objective data from an online registry can be analyzed using machine learning methodologies to provide an accurate prediction of the brain amyloid beta (Aß) status of registry participants.

Method

We developed and optimized machine learning models using data from up to 664 participants in the Brain Health Registry. Models were assessed on their ability to predict Aß positivity using the results of positron emission tomography as ground truth.

Result

The optimal feature set included gender, study partner‐assessed Everyday Cognition score, and the Cogstate Brief Battery’s One Card Learning test and resulted in a cross‐validated AUC score of 0.75.

Conclusion

Inclusion of study partner assessments and certain Cogstate Brief Battery scores increases the ability of machine learning models to predict Aß positivity.
Effects of lifestyle on the health, depression, and quality of life of middle‐aged and elderly before and after COVID‐19: Structural equation modeling
Authors: Yang Min Ah , Park Ji‐Hyuk
Published: December 2021

Background

The purpose of this study is to identify the effects of the lifestyle (physical activity, activity participation, and nutrition) of middle‐aged and elderly people on health, depression, and quality of life, and to identify changes before and after COVID‐19. In addition, it is intended to establish a structural equation model to confirm the influence coefficients for each path.

Method

Among those aged 55 and older, the study measured lifestyle, subjective health, depression, and quality of life for a total of 327 people. We used SPSS 25 for general characteristics of subjects, descriptive statistical analysis of variables, and AMOS 20 for validation of variables, affirmative factor analysis, and effectiveness analysis on paths.

Result

In the case of physical activity, there were significant differences between the two groups in moderate exercise (p<0.001) and walking (p<0.01) before and after COVID‐19. The results of participation in activities showed significant differences between leisure activities, social activities and education before and after COVID‐19 (p<0.001). For eating habits, significant differences were found in the two observations: carbohydrate (p<0.05) and protein (p<0.05). Comparing the overall mean, there were significant differences between health (p<0.05), depression (p<0.001), and quality of life (p<0.001) before and after COVID‐19. The final model was built through normality test and confirmatory factor analysis, and the fit of the final study model was x²=3.306, GFI=0.902, RMR=0.049, RMSEA=0.059, IFI=0.928, TLI=0.917, CFI=0.928, which was appropriate compared to each criterion, showed significance for each path.

Conclusion

Through this research, it was confirmed that lifestyle affects health, depression, and quality of life for middle‐aged elderly people, which is in the same context as prevention‐oriented policies currently in place worldwide. In addition, the results of this study show the importance of a healthy lifestyle, suggesting that lifestyle education for middle and high‐aged people and customized lifestyle interventions for individual lives are needed. Comparisons between the two periods before and after COVID‐19 show that the social isolation caused by COVID‐19 has a negative impact on each factor. Through these results, health care is essential for middle‐aged and elderly people, and measures should be taken to resolve restrictions on participation in activities caused by social isolation.
Gender difference of cerebrospinal fluid ceruloplasmin in mild cognitive impairment
Authors: Wang Lijun , Liu Jun
Published: December 2021

Background

The underlying mechanisms of brain oxidative stress and neuroinflammation, an invariant neurodegenerative features that correlate with cognitive function and the progression of Alzheimer’s disease (AD), remains elusive. Ceruloplasmin (Cp) is a protein that intersects these pathways. The role of Cp in AD and its potential use as a biomarker has not been identified. The purpose of the study is to explore the impact of gender on cerebrospinal fluid (CSF) ceruloplasmin concentrations in patients with mild cognitive impairment (MCI).

Method

Seventy‐one males and 33 females with MCI from the AD Neuroimaging Initiative (ADNI) were included in the study. We explored the gender discrepancies in CSF ceruloplasmin levels, volumes of hippocampus, entorhinal cortex (EC), fusiform and medial temporal lobe (MTA).

Result

The results showed that CSF ceruloplasmin levels were significantly higher in males compare to females in MCI patients (P = 0.011). No gender differences were found in CSF Aβ42, CSF Tau and CSF P‐tau (P = 0.496, P = 0.096, P = 0.070). Females showed reduced volumes of the EC, fusiform and MTA (P = 0.010, P < 0.001, P < 0.001) than males. However, volumes of the hippocampus between the males and females in MCI did not differ (P = 0.099).

Conclusion

These findings suggest that gender discrepancies should be considered in the interpretation of CSF ceruloplasmin when evaluating MCI.
Apolipoprotein E polymorphism in Kazakhstani population with Alzheimer’s disease
Authors: Kaiyrlykyzy Aiym , Baibulatova Aida , Olzhayev Farkhad , Tsoy Andrey , Davletov Kairat , Askarova Sholpan
Published: December 2021

Background

Advanced age, apolipoprotein E ε4 (APOE) and gender are well‐known risk factors for Alzheimer's disease (AD). At least one copy of APOE‐ε4 is present in around 60% of AD cases (1). However, there are worldwide variations of APOE‐ε4 carriers by region and by ethnicity (2). There is no available data on distribution of APOE polymorphism among Alzheimer’s patients in Kazakhstan. Thus, we assessed the apolipoprotein E allele and genotype frequencies in patients with Alzheimer’s disease and compared them to normal controls.

Method

We included 53 AD patients and 99 people with normal cognition recruited from city hospital in Astana, Kazakhstan. APOE genotypes were determined by Real Time PCR using TaqMan® SNP Genotyping Assays.

Result

The APOE‐ε4 allele frequencies were found to be 82.7% for ε3, 1.9% for ε2, 41.5% for ε4 in AD group, and 92.9% for ε3, 8.1% for ε2 and 25.2% for ε4 in the control group. Genotype ε4/ε4 was found in 9.4% of AD patients compared to 1% in controls (p<0.005) Genotypic distribution of APOE polymorphism did not differ between gender in study group, however, APOE‐ε4 carrying status was significantly different by ethnic groups (p=0.04), where Kazakhs had 34.3% of APOE‐ε4 carriers, Russian and other ethnic groups 16.6% and 17.6% respectively.

Conclusion

This is the first study of APOE polymorphism distribution in AD patients in Kazakhstan. APOE ε4 carrier frequency was similar to other Asian and Central European populations. Our findings are consistent with previous literature on the significance of the subjects' geographical region and ethnic context in the study of APOE genotypes in association with AD. Reference: 1. Riedel BC, Thompson PM, Brinton RD. Age, APOE and sex: Triad of risk of Alzheimer's disease. J Steroid Biochem Mol Biol. 2016 Jun;160:134‐47. doi: 10.1016/j.jsbmb.2016.03.012. Epub 2016 Mar 8. PMID: 26969397; PMCID: PMC4905558. 2. Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL, Arrighi HM. Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta‐analysis. Dement Geriatr Cogn Disord. 2011;31(1):20‐30. doi: 10.1159/000321984. Epub 2010 Dec 1. PMID: 21124030.
Ophthalmic pathology in patients with primary neurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna
Published: December 2021

Background

The priority problem of modern healthcare is irreversible dementia due to the steady increase in morbidity, which leads to disability and complete dependence of the patient on others. Among irreversible dementias, Alzheimer's disease takes the first place. Most often, only with sufficiently pronounced cognitive disorders, the doctor can diagnose Alzheimer's disease, although it is obvious that the neurodegenerative process begins even before the clinical manifestations of the disease. Due to the common origin of the eye and the brain, we can say that the eye is a "window to the brain". Many scientists note the similarities between gerontophthalmological diseases and Alzheimer's disease.

Method

The study examined 60 patients who were divided into 2 groups: the first group included patients with Alzheimer's disease who met the criteria of NINCDS ADRDA, the second group included patients with vascular dementia who met the criteria of NINDS‐AIREN. These groups are fully comparable by gender and age. Each group included 9 men and 21 women, with an average age of 65.5 years. All patients underwent a comprehensive neuropsychological examination, using the short Mental Status Assessment Scale (MMSE), the Montreal Cognitive Function Assessment Scale (MoCA), the battery of tests for assessing frontal dysfunction (FAB), the clock drawing test. Also, all patients underwent ophthalmological examination of the visometry, measurement of intraocular pressure, examination of the anterior segment of the eye and fundus, and spectral optical coherence tomography.

Result

In the course of the study, significant ophthalmic pathology was detected in the group with neurodegenerative changes ‐ age‐related macular degeneration was found in 16.7%, pseudoexfoliative syndrome‐20%, primary open‐angle glaucoma‐46.7%. This means that the risk of developing gerontophthalmological diseases increases in patients with neurodegenerative disorders. Therefore, we can assume that the retina is a mirror of neurodegenerative changes in the brain, which will allow to diagnose the disease at early stages and with the help of drug therapy to delay further development of the disease, resulting in reduced disability for patients and socio‐economic costs of society.

Conclusion

The results obtained are promising for the early diagnosis of primary neurodegenerative diseases and indicate the need for further research on this topic.
A population‐based study on awareness of young adults regarding the role of physical exercise in improving brain health in Turkey
Authors: Menengiç Kübra Nur , Güngör Feray , Ovacık Uğur
Published: December 2021

Background

Exercise is known for many benefits such as cardiovascular fitness, muscle strength and endurance, and reduction of adipose tissue. It is known that exercise has many important health‐related effects, but it is a question mark whether there is awareness about its positive benefits on brain health and dementia, which has become one of the increasing problems of the developing world. The aim of this study was to determine the level of awareness about the effects of exercise on brain health.

Method

361 participants were included in the study. Informed consents of the participants were obtained. The socio‐demographic information of the participants was recorded and six questions were asked about exercise and brain health. The answers were evaluated over 3 options, “yes”, “no” and “not sure”. It was also questioned whether the participants exercised regularly or not.

Result

Demographic characteristics of the participants are presented in Table 1 and the percentages of the answers given to the questions about the effects of exercise on brain health are shown in Table 2. The awareness of the role of exercise on brain health was found to be high. However, only 18.6% of the participants have been exercising regularly for more than 6 months.

Conclusion

Participants are aware of the effects of exercise, but this is not enough to motivate them to perform exercise and physical activity regularly. It becomes important to identify the barriers and facilitating factors for exercise participation. In addition, most of the participants were not aware of the World Health Organization's recommendation of ≥150 minutes of moderate intensity or ≥75 minutes of high‐intensity aerobic physical activity throughout the week and muscle strengthening activities on ≥2 days a week. The content of awareness studies aimed at preventing or delaying the onset of dementia is important. It is necessary to increase the informative studies on the dose, intensity and frequency of exercise required for maintaining health and for diseases such as dementia.