bluuebunny/crossref_metadata_2025 huggingface dataset:
Balance, movement confidence, and cognition: Exploring the impacts of a group motion‐based technology intervention for people with dementia and mild cognitive impairment
Authors: Dove Erica , Wang Rosalie , Zabjek Karl , Astell Arlene J.
Published: December 2021

Background

Exercise can impact balance, movement confidence, and cognition among people with dementia and mild cognitive impairment (MCI). However, engaging and accessible ways for this population to exercise are lacking. Motion‐based technology, which people with dementia and MCI can learn to use and enjoy using, could be a potential solution. The purpose of this study was to examine the impacts of a group motion‐based technology intervention on balance, movement confidence, and cognition among people with dementia and MCI.

Method

Participants with dementia and MCI (n=28; 53.6% female) were recruited from four community‐based adult day programs and invited to partake in a 10‐week Xbox Kinect bowling intervention. Before and after the intervention, participants completed the Montreal Cognitive Assessment (MoCA) and the Mini Balance Evaluation Systems Test (Mini‐BEST) to measure cognition and balance, respectively. Video recordings were taken during the first, middle, and final week of the intervention and coded using video analysis software, to measure movement confidence. Quantitative data from the MoCA, Mini‐BEST, and coded video recordings were compared using a series of related‐samples Wilcoxon signed rank tests.

Result

At baseline, participants with dementia and MCI were substantially impaired with regards to balance (mean Mini‐BEST: 14.58/28), cognition (mean MoCA: 12.86/30), and mobility (57.1% mobility device users). Among the participants who completed the study, there was no significant decline in balance (Z‐score=‐1.276, p=0.202), movement confidence (Z‐score=‐0.359, p=0.719), or cognition (Z‐score=‐0.060, p=0.952), suggesting a potential maintenance effect of the intervention.

Conclusion

Firstly, the findings highlight the prevalence of mobility and balance impairments among people with dementia and MCI, in addition to confirming their cognitive impairment. Secondly, this study also highlights the potential of using motion‐based technology to support the function and well‐being of people with dementia and MCI. That is, the finding of no significant decline in function among the participants can be considered a positive finding, given the generally progressive nature and trajectory of dementia.
Associations between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status in the spectrum of Alzheimer’s disease
Authors: Kaplan Elizabeth , Correia Stephen , Oh Hwamee
Published: December 2021

Background

Recent studies have found that individuals who have undergone psychological stress and/or are affected by a chronic stress‐related disorder have an increased risk of developing Alzheimer’s Disease (AD). However, currently the biological mechanism underlying this relationship remains elusive. We hypothesized that white matter integrity loss may be a potential mediator between psychological stress and the development of AD. The goal of this study was to examine the relationship between neuropsychiatric symptoms as a proxy of stress responses, white matter microstructural integrity, and diagnostic status along the spectrum of AD.

Method

We evaluated the relationship between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status along the spectrum of AD in 133 participants (ages 55.2‐90.4 years) selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI‐2). Total scores in a brief Neuropsychiatric Inventory Questionnaire (NPI‐Q) were used to represent individuals’ psychological stress responses. We quantified white matter integrity measures using diffusion tensor imaging scans processed by the FMRIB's Diffusion Toolbox followed by the FSL Tract‐Based Spatial Statistics toolbox.

Result

NPI‐Q scores representing stress responses significantly differed across diagnostic groups. Specifically, patients with AD (N=40, mean age=74.39) showed significantly higher NPI‐Q scores compared with cognitively normal (CN) older adults (N=44, mean age=73.39) and patients with Mild Cognitive Impairment (MCI)(N=49, mean age=75.64). Whole brain voxel‐wise analyses with white matter integrity measures as quantified as fractional anisotropy (FA) and mean diffusivity (MD) showed significant FA and MD differences (p ≤ 0.01) in the splenium, cingulum, superior longitudinal fasciculus, posterior thalamic radiation and the corpus callosum regions when controlling for age and sex. These differences were greater for AD patients compared with CN participants than those with MCI. NPI‐Q scores, however, were not related to a degree of white matter integrity in this sample.

Conclusion

Significant group differences are shown in stress responses and white matter integrity across the diagnostic groups in the AD spectrum, which is consistent with the literature. Future studies are warranted to integrate reliable biological markers of stress responses to assess the impact of stress responses on microstructural changes and AD pathologies.
Brain functional connectivity during visual short‐term memory binding after cognitive training in preclinical phases of dementia
Authors: Soto Marcio , Camlla Rosangela , Vilca Brenda Chino , Parra Mario A.
Published: December 2021

Background

Neuroimaging studies have shown changes in functional connectivity after cognitive training in preclinical phases of dementia. What is not yet clear is the neurophysiological aspects of these changes. Our objective was analyze the effect of cognitive training on brain functional connectivity during visual short term memory binding (VSTMB) task in preclinical phases of dementia.

Method

The final sample was composed of 5 older adults with subjective cognitive decline (mean age = 62.08, SD = 6.48) and 4 with mild cognitive impairment (mean age = 62.93, SD = 6.75). All participants underwent assessment with VSTMB test (shape only and shape‐color) while we recorded their EEG with 160‐channel system (Brain Vision ActiChamp), at baseline and 3 months after cognitive training. The program lasted 24 sessions and was focused on attention, executive function and memory domains.

Result

We found a significant improvement of visuospatial memory at behavioral level (p<.05). In shape only test phase, we found a post training activity diminution in fronto‐central right ROIs, in intermediate and late time windows (FDR p < .05), an enhancement in fronto‐central right ROI and early time window (FDR p < .05) and parietal‐posterior left ROI in late time windows (FDR p<.05). In shape‐color binding condition, significant differences were found for encoding phase presenting post training activity enhancement for fronto‐central left ROI in intermediated and late time windows (FDR p < .05).

Conclusion

Cognitive training changed functional connectivity in anterior and posterior regions during shape only test phase. During shape‐color condition there was a connectivity increased in anterior regions during encoding phase. These findings are discussed in the light of cognitive and neurophysiological aging models.
Diet and resting state brain functional connectivity across the adult lifespan
Authors: Gu Yian , Burns Eleanna , Habeck Christian , Mensing Ashley , Noofoory Diala , Babukutty Reshma S , Stern Yaakov
Published: December 2021

Background

Healthy diets are associated with reduced risk of Alzheimer’s disease, better cognition, and healthier brain structural measures. However, the relationship between nutrition and diet and resting‐state functional connectivity (rsFC) remains unclear.

Method

The current study included 370 individuals across the adult lifespan (20–80 years). Dietary information was self‐reported using a food frequency questionnaire, from which the Mediterranean diet score (MeDi, range 0‐55) was calculated. Participants underwent a resting‐state imaging on a 3T MRI scanner. Within‐network and between‐network connectivity values were computed based on 10 predefined networks. Multivariable linear regression models were used to examine the association between tertiles of MeDi and rsFC in the overall study population as well as within three age groups [99 young (20‐45 years); 147 middle‐aged (46‐65 years), and 124 older adults (66‐80 years)]. Similar analyses were done for omega‐3 polyunsaturated fatty acids (PUFA) consumption. All models were controlled for potential confounders including age, sex, education, race/ethnicity, caloric intake, IQ, and scrubbing percentage.

Result

Among all subjects, higher MeDi was associated with lower global within‐network connectivity (highest vs. lowest tertile of MeDi, b=‐0.014, p=0.031) but not with global between‐network connectivity. Among all ten individual networks, higher MeDi was associated with lower within‐network connectivity of the default‐mode network (DMN) but not with any other individual networks. Analyses stratified by age groups found the associations between rsFC and diet could mainly be seen in older adults. Among the somatomotor networks, higher MeDi was associated with higher within‐network connectivity for hand and auditory networks but was associated with lower within‐DMN connectivity. For between‐network connectivity, higher MeDi was associated with higher global connectivity (highest vs. lowest tertile of MeDi, b=0.019, p=0.015) as well as higher connectivity for almost all individual networks except for the DMN. No association between MeDi and rsFC was found in younger and middle‐aged adults. Findings on omega‐3 PUFA were similar to MeDi, except that omega‐3 PUFA was not associated with within‐network connectivity of the DMN.

Conclusion

Our findings suggest that in older adult, healthier dietary factors are associated with higher both within‐ and between‐ network connectivity except for within‐DMN rsFC values.
The utility of the Oral Trail Making Test in telehealth assessments with cognitively impaired older adults
Authors: Saurman Jessica L. , Vickers Kayci L. , Rodriguez Amy D. , Andrews Morgan , Gradone Andrew M. , Jean Kharine R. , Goldstein Felicia C
Published: December 2021

Background

Due to the recent COVID‐19 pandemic, many clinicians have transitioned to telehealth‐based cognitive assessments as a practical alternative to in‐person evaluations. Meta‐analysis has shown that verbally‐mediated measures of cognition are the most easily adapted to telehealth administration, while measures that include visual or motor components are more variably impacted. The Oral Trail Making Test (O‐TMT) is one verbal measure of executive function that removes motor and visual demands. However, there is a dearth of research related to the use of the O‐TMT in cognitively impaired older adults to evaluate executive function. Therefore, this project aimed to examine the relationship between O‐TMT scores with other neuropsychological measures in individuals with cognitive impairment.

Method

Forty‐one participants enrolled in the Emory Cognitive Empowerment Program underwent telehealth‐based neuropsychological assessment that included the O‐TMT. The O‐TMT is comprised of two parts. Part A requires individuals to count out loud from 1 to 25 and is primarily a measure of processing speed and simple attention. Part B requires individuals to alternate saying numbers and letters (1‐A, 2‐B, etc.) and is a measure of mental flexibility. Time to completion as well as total errors are captured during administration. Participants also completed the Montreal Cognitive Assessment (MoCA) as a measure of global cognitive function, a measure of practical reasoning (Test of Practical Judgement), and a self‐report measure of cognitive change (Everyday Cognition). Correlational analyses were completed to examine the relationship between O‐TMT scores and global cognitive function, practical judgment, and subjective cognitive status.

Results

The sample consisted of older adults (Mage = 72.84, SDage = 8.20) who were well‐educated (Myears = 16.07, SDyears = 2.22). O‐TMT Part B Time to Completion was moderately correlated with total MoCA score (r = ‐0.36, p = 0.03), such that slower performance was associated with poorer overall cognitive function. The O‐TMT was not significantly correlated with practical judgment or subjective cognitive status.

Conclusion

Results of the current study indicate poorer performance on the O‐TMT part B is associated with poorer overall cognitive function on the MoCA. Future research should examine the sensitivity and specificity of the O‐TMT part B for individuals who are cognitively impaired.
Ambient air pollutants and indoor air quality are associated with cognitive impairment in older adults: A six‐year cohort study
Authors: Tsao Shu‐Ping , Chen Jen‐Hau , Chen Jia‐Kun , Yu Hwa‐Lung , Chiou Jeng‐Min , Yeh Su‐Ling , Chen Ta‐Fu , Chen Yen‐Ching
Published: December 2021

Background

Exposure to air pollutants have known to increase the risk of cognitive impairment. Some older adults spend a long time indoors. However, limited studies have evaluated the effect of time staying indoors on the association between exposure to ambient air pollutants and cognitive function in older adults.

Method

This cohort study is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (2011‐present). A total of 605 older adults were recruited at baseline (2011‐2013) with three biennial follow‐ups, and 496 participants were included after exclusion. The data of six air pollutants including sulphur dioxide, nitrogen dioxide, particulate matter in diameter ≤ 2.5µm (PM2.5) and 2.5‐10µm (PMcoarse), carbon monoxide, and ozone were obtained from 26 monitor stations of Taiwan Environmental Protection Administration (TEPA) between 1993 and 2019. Spatial‐Time Analysis Rendering with Bayesian Maximum Entropy was utilized to estimate the individual air pollutants’ exposure. Hours staying indoors were collected across four seasons. Generalized linear mixed model was utilized to explore the association between long‐term exposure to air pollutants and global or domain‐specific cognitive function (memory, attention, executive function, and language) over 6 years adjusted for some covariates. Stratified analyses were performed by median hours staying indoors every day.

Result

The mean age of the study participants were 72.4 years at baseline. PM2.5 was the only pollutant with a 14‐year average level (29.0 µm/m3) higher than the TEPA air quality standards. An interquartile range (IQR) increase in PM2.5 was associated with poor global cognition (β=‐0.19) and executive function (β=‐0.08), and the former effect became more evident in those with hours staying indoors < 13 hours/day (β=‐0.31). An IQR increase in PMcoarse was associated with poor global cognition (β=‐0.21) and verbal fluency (β=‐0.10), which became more evident in those stayed indoors ≥13 hours/day (β=‐0.32 and ‐0.13, respectively). Exposure to PMcoarse was associated with poor attention (β=‐0.15). No significant association was observed between other air pollutants and the performance of logical memory.

Conclusion

Long‐term exposure to PM2.5 or PMcoarse showed detrimental effect on cognitive function in community‐dwelling older adults and indoor air quality may play a role on these associations.
Risk prediction of prodromal Alzheimer’s disease using deep learning of MRI scans
Authors: Basha Shaikh , Marizzoni Moira , Frisoni Giovanni B , Jovicich Jorge , Miyapuram Krishna P
Published: December 2021

Background

Deep learning approaches for classification have the advantage of automatically learning the relevant features but require large amount of data for training. We test the efficacy of deep learning approach for prediction of risk factor for prodromal Alzheimer’s disease from whole brain MRI scans segmented into grey/white matter and CSF images.

Method

Longitudinal MPRAGE images were acquired from 146 participants in six month intervals over a period of two years as part of PharmaCog Consortium. Whole brain structural scans were segmented using FreeSurfer pipeline into grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) images. We used a convolutional neural network architecture with 11 layers to classify individuals with high and low risk based on 3‐dimensional MRI data. The model consisted of 3 convolution layers that performed slice wise convolutions in 2‐dimensions, 3 batch normalization layers, 1 max pooling layer, 1 flatten layer, 2 dense layers and 1 rectified linear unit (ReLU) activation layer. Hyperparameter tuning for the model was done using various combinations of kernel size ([2,3,4]), strides ([1,2,3]), batch size ([5,10,15,20]), epochs ([10,15,20]) and number of neurons in the dense layer ([16,32,64]) to identify the optimized parameters for the model.

Result

Out of the 146 subjects available, we chose 97 subjects randomly. The cross‐sectional MRI data at various timestamps was considered for training the model. The rest of the data was considered as the test set. After this separation, we had training size and test size of 436 and 168 images respectively. The training and test sets did not have any common subjects and thus provided relevant results for subject wise classification for unseen subjects.

We trained and tested our model with all possible combinations of segmented images separately (GM, WM, CSF, GM+WM, WM+CSF, GM+CSF, GM+WM+CSF). Out of all the combinations, we attained best results using Grey mask (GM) data, with training and test accuracies of 93.62% and 72.02% respectively.

Conclusion

We presented a deep learning framework for risk prediction of cross‐sectional whole brain MRI data for unseen subjects. This work combined with classification approaches on longitudinal data can prove effective in early diagnosis of Alzheimer’s disease.
Clinical characterization of Colombian families with frontotemporal dementia due to the MAPT P397S mutation
Authors: Zuluaga‐Castaño Yesica , Aguillon David , Rassi Sofia , Zuluaga Maria , Gómez‐Henck Clara , Lopera Francisco , Quiroz Yakeel T.
Published: December 2021

Background

Mutations in the microtubule associated protein tau (MAPT) gene located in chromosome 17 have been associated with frontotemporal dementia (FTD). The novel mutation Pro397Ser, with an autosomal dominant inheritance pattern has been recently reported in Spain (Borrego‐Écija et al., 2019). The Group of Neuroscience of the University of Antioquia in Colombia has identified several families with mutations leading to FTD. Here we present the initial clinical characterization of individuals carrying the MAPT P397S mutation.

Method

A total of 30 family members were included (15 carriers and 15 non‐carriers, 18 – 76 years old). All participants underwent a comprehensive neurological and neuropsychological evaluation. They also completed self‐reported measures of depression and behavioral symptoms. Mann‐Whitney tests were used to test between‐group differences in cognitive measures. Spearman correlations were used to examine associations among outcome measures and age.

Result

Mean age was 48.7 years (SD 16.4), and mean education was 10.7 years (SD=4.56). Six carriers were classified as cognitively impaired (MCI= 3, moderate/severe dementia= 3). Mean age of clinical was 50 years. Initial symptomatology was predominantly behavioral (disinhibition, aggressiveness, loss of empathy, compulsiveness, dietary changes) followed by loss of executive function, memory, language skills and decline in ADLs in affected individuals. Structural MRIs showed frontotemporal lobar degeneration in all impaired carriers, and additional bilateral hippocampal atrophy with left predominance in two of them. The cognitive profile of carriers was characterized by lower scores in measures of executive function, semantic processing and short‐term memory loss. Cognitively unimpaired carriers had statistically significant worse performance on the INECO Battery, a measure of executive function, compared to non‐carriers, several years prior to their clinical onset.

Conclusion

Initial findings showed that the clinical profile of Colombian families with the MAPT‐P397S novel mutation is characterized by executive dysfunction, behavioral changes, semantic language alterations and memory loss. Findings suggest that the INECO Battery may be a sensitive tool to detect subtle changes in executive function in cognitively unimpaired carriers of this mutation. Longitudinal follow‐up of these individuals will be important to better characterize the disease progression from preclinical to clinical stages. Future studies should consider adding neuroimaging and other biomarker measures.
In vivo analysis of synaptic degeneration with Aβ plaque and NFT accumulation in cognitive decline
Authors: DiFilippo Alexandra H. , Tullis Tyler , Zammit Matthew D. , Murali Dhanabalan , Kohli Akshay , Ennis Gilda E. , Davenport Nancy J. , Barnhart Todd E. , Engle Jonathan W. , Betthauser Tobey J. , Stone Charles K. , Johnson Sterling C. , Bendlin Barbara B , Christian Bradley T.
Published: December 2021

Background

[11C]UCB‐J selectively binds to synaptic vesicle glycoprotein 2A (SV2A) and may be used to measure synaptic density in synaptopathies. Along with the accumulation of amyloid‐b plaques and neurofibrillary tau tangles, neurodegeneration is a hallmark of Alzheimer’s disease (AD) dementia. Synaptic density may be decreased due to AD pathology, resulting in cognitive dysfunction. We examined whether synaptic density was related to the accumulation of protein aggregates characteristic of AD as well as cognitive function.

Method

Thirty subjects (68.6±6.2 years old, 20F/10M) recruited from the Wisconsin ADRC and the Wisconsin Registry for Alzheimer’s Prevention study underwent [11C]UCB‐J dynamic PET imaging to assess synaptic density, T1w‐MR imaging, and the Rey Auditory Verbal Learning Test (RAVLT). Twenty‐four participants also completed [11C]PiB dynamic imaging to assess amyloid‐b plaque accumulation and [18F]MK‐6240 dynamic imaging to assess neurofibrillary tangle accumulation. T1w‐MRI was used to derive subject‐specific regions of interest (ROIs) as well as to calculate the matrices required to transform images into MNI152 space. Global amyloid burden was ascertained by taking the mean PiB DVR across eight bilateral AAL‐based ROIs. Neurofibrillary tau tangle accumulation in the entorhinal cortex was quantified using the [18F]MK‐6240 SUV ratio. Subject‐specific hippocampus ROIs for [11C]UCB‐J analysis were defined using FreeSurfer (v7) segmentation of the participant’s MR image.

Result

Using data from the n=24 subjects, [11C]UCB‐J binding in the hippocampus was significantly associated with [11C]PiB global DVR (R2 = 0.24, P = 0.01) and [18F]MK‐6240 uptake in the entorhinal cortex (R2 = 0.17, P = 0.04). After correcting for hippocampus volume size, significance decreased for both measures (R2 = 0.28, P = 0.05 for [11C]PiB global DVR; R2 = 0.17, P = 0.05 for [18F]MK‐6240 entorhinal cortex SUVR). [11C]UCB‐J binding in the hippocampus was not significantly related to RAVLT immediate recall (R2 = 0.52, P = 0.08) but was significantly associated with RAVLT delayed recall (R2 = 0.55, P = 0.04).

Conclusion

Findings suggest that synaptic impairment is related to amyloid‐b and neurofibrillary tau tangle accumulation as well as worse performance on RAVLT delayed recall. Future work will test the longitudinal relationship between accumulation of AD pathology, synapse loss, and cognitive decline.
REACTION: Reducing the effects of aging on cognition with therapeutic intervention of an oral nutrient — A pilot interventional study for age‐related cognitive decline
Authors: Camargo Christian , McInerney Katalina , de Wilde Janneke , Counotte Danielle , Rundek Tatjana
Published: December 2021

Background

Age‐related cognitive decline (ARCD) refers to the cognitive changes that can occur in individuals as a consequence of aging, distinct from cognitive changes due to a primary neurodegenerative process (e.g., Alzheimer’s Disease), cerebral ischemia (e.g., vascular dementia), or other pathology. However, there is sparse research into direct interventions for ARCD. Recent research suggests that the underlying mechanism behind ARCD is a loss of synaptic plasticity, which is essential for learning, memory, and the formation of memory engrams, in part through its effects on dendritic spine morphology. Therefore, therapies aimed at rescuing dendritic spine density and increasing synaptic plasticity may be viable strategies for decreasing the effects of ARCD. Souvenaid contains Fortasyn Connect, a specific combination of nutrients designed to enhance synapse formation by providing precursors and cofactors for phospholipid synthesis. In prodromal Alzheimer’s disease, Fortasyn Connect showed beneficial effects on memory, cognition, and brain atrophy [1]. In addition, the data from this study suggest a stronger effect would be expected in participants at earlier stages of prodromal AD. Souvenaid has not yet been tested in individuals with ARCD.

Method

Towards this end, we present the design of a 6‐month single‐center pilot clinical trial that aims to perform all assessments via a telemedicine platform. The study design specifically factors in local COVID‐19 restrictions. We plan to recruit 60 participants aged 55‐89 with age‐related cognitive decline, who will be screened and randomized to the oral multi‐nutrient combination (Souvenaid) or placebo on a 1:1 basis. The main outcome of this trial is feasibility (recruitment rate and time, adherence rate and retention rate). Other outcomes include memory (e.g. Ray Verbal Learning Task), cognition (e.g. Oral Trail Making Test), and quality of life (e.g. Amsterdam IADL Questionnaire) outcome measures.

Result

Results of REACTION will provide insight into the feasibility of a virtual study with Souvenaid in ARCD.

Conclusion

With the rapidly growing prevalence of ARCD and no pharmacological interventions currently available, nutritional interventions may potentially play an important role to reduce or delay the effects of ARCD.
Differential measurement of depression by racial group: Findings from an Alzheimer’s Disease Center cohort
Authors: Umucu Emre , Wyman Mary F. , Zuelsdorff Megan , Lambrou Nickolas H. , Summers Marlene , Strong Lois , Martin Wesley , Carter Fabu P , Bouges Shenikqua , Gleason Carey E.
Published: December 2021

Background

Both researchers and clinicians require risk screeners that are psychometrically‐sound and culturally‐appropriate in addition to being efficient and low‐burden. Brief versions of the Geriatric Depression Scale (GDS) exist, but there is limited study on the performance of these screeners across historically underserved and underrepresented racial groups. We examined the ability of 10 brief versions of the GDS to detect group differences in depressive symptom endorsement and to predict cognitive status in White, Black, and American Indian/Alaska Native (AI/AN) participants in an ADC‐based cohort.

Method

Participants included 555 cognitively‐normal middle‐aged and older‐adults (Mage
=60.85) enrolled in the Wisconsin ADRC. The majority of participants were female (66.5%). 17.7% of participants were Black and 3.1% were AI/AN. For each GDS version, we used Kruskal‐Wallis tests with post‐hoc‐pairwise comparisons with Bonferroni corrections to compare scores across the three groups.

Result

Using nine of 10 GDS versions, there were significant group differences in total score. Post hoc pairwise comparisons revealed that AI/AN endorsed significantly fewer symptoms of depression than Blacks (p < 0.05) when using the GDS‐4a. Whites and Blacks were not significantly different in GDS‐4a. However, Whites and Blacks were different in eight of 10 versions (i.e., GDS‐1a; GDS‐4b; GDS‐5; GDS‐7; GDS‐8; GDS‐10a; GDS‐10b; GDS‐15). No group differences were found between Whites and AI/AN and Blacks and AI/AN in most versions of the GDS. In the combined sample, all GDS versions showed a significant, moderate positive correlation with CDR score.

Conclusion

Rigorous assessment and detection of depression is an important step to reducing dementia morbidity and possibly risk, but many brief screeners were evaluated in racial homogenous groups. Most GDS short versions were able to detect significant differences in depression score between Whites and Blacks. Interestingly, the GDS‐4a (4 non‐behavioral items) showed significant difference between AI/AN and Blacks, not detected in other versions. These early findings suggest that more research must address culturally‐valid assessment of depressive symptoms in cognitive aging research and geriatric clinic settings. Acknowledgement: Data collection and contributions by author Carey E. Gleason are supported by funding from NIH‐NIA for African Americans Fighting Alzheimer’s at Midlife (AA‐FAIM, R01 AG054059) and the Wisconsin Alzheimer’s Disease Center (P50 AG033514).
Cognitive aging with dementia, mild cognitive impairment (MCI), or no impairment: A comparison of same‐ and other‐sex couples
Authors: Correro Anthony N , Gauthreaux Kathryn , Perales Jaime , Kukull Walter A , Flatt Jason D
Published: December 2021

Background

Chronic stress has harmful effects on cognition, and minority stress is thought to underlie health disparities experienced by lesbian, gay, bisexual, and transgender (LGBT+) older adults. Few studies have compared cognitive trajectories between individuals in same‐ (SSR) versus other‐sex relationships (OSR). We expand on this work by comprehensively examining differences in neuropsychological measurements for individuals in SSR and OSR. We explored whether: 1) SSR have poorer overall cognitive performance at baseline compared to OSR older adults, 2) SSR have steeper cognitive decline relative to OSR, and 3) differences in verbal and visuospatial memory among SSR versus OSR.

Method

Data were obtained from the National Alzheimer’s Coordinating Center (NACC). Eligibility criteria included 2+ visits in NACC’s Uniform Data Set (UDS) and age 55+ years at baseline. Participants were assigned to normal (N), MCI, or dementia (D) groups based on clinician assessment and CDR® global score. Given neuropsychological tests changed between versions of the UDS, we ran analyses separately using both versions (C1, C2). Multivariable linear mixed‐effects models accounted for center clustering and repeated measures by individual. Models were stratified by baseline cognition and adjusted for baseline age, sex, education, and APOE ɛ4 carrier status.

Result

OSR and SSR individuals showed significant decline in CDR® sum of boxes (CDR‐SB) regardless of baseline cognition. Among C1 participants, OSR declined significantly in all cognitive domains regardless of baseline cognition. SSR‐N declined in the attention, executive, and language/semantic memory (SM) domains; SSR‐MCI showed declines in global, attention, and language/SM domains; similar to OSR‐D, SSR‐D declined in all domains. Unexpectedly, SSR‐D declined more slowly than OSR‐D in attention and language/SM domains. Among C2 participants, OSR exhibited greater levels of decline in global cognition relative to SSR.

Conclusion

We sought to compare the cognitive changes of older adults in SSR or OSR. SSR declined in attention, language, and semantic memory. OSR had steeper, more global declines. Our results contrast with a recent population‐wide study of SSR versus OSR, suggesting that in our sample, SSR may be resilient to the effects of chronic minority stress on cognition. Additional research regarding LGBT+ related resiliency is necessary.
Updated prevalence estimates of amyloid positivity from cognitively normal to clinical Alzheimer’s disease dementia: The Amyloid Biomarker Study
Authors: Janssen Olin , Jansen Willemijn J , Tijms Betty M , Maserejian Nancy Nairi , Ossenkoppele Rik , Verhey Frans RJ , Visser Pieter Jelle ,   the Amyloid Biomarker Study group
Published: December 2021

Background

We have updated our previous amyloid positivity prevalence estimates (Jansen, 2015; Ossenkoppele, 2015; Table 1) with data from 19,097 individuals from 85 cohorts. We tested if prevalence estimates differed for positron emission tomography (PET) or cerebrospinal fluid (CSF) amyloid. We calculated data‐driven CSF cut‐points as previous studies suggested a drift in Innotest‐assay performance.

Method

We included 9,908 participants with normal cognition (CN); 1,542 with subjective cognitive decline (SCD); 5,405 with mild cognitive impairment (MCI); and 2,260 with clinical Alzheimer’s disease (AD) dementia. 10,139 participants had an amyloid‐PET measure and 8,958 participants had an amyloid‐CSF measure. Amyloid‐ß aggregation was originally dichotomized as normal or abnormal according to study‐specific cut‐points, and we defined data‐driven CSF cut‐points using Gaussian mixture modelling. Generalized‐estimating‐equations adjusting for within‐study clustering of individuals were used to estimate amyloid positivity prevalence according to age, cognitive status, and biomarker modality and compared original with updated cut‐points.

Result

Amyloid positivity prevalence was higher with older age and advancing disease severity. Using original cut‐points as provided by the cohort, the prevalence of amyloid positivity at the median age of 70 was similar for PET and CSF estimates for CN (24%), SCD (26%), and MCI (51%), and was higher in PET (87%) than CSF (79%) for clinical AD dementia. Using the data‐driven CSF cut‐points, the prevalence of amyloid positivity was higher for CSF‐based estimates than PET‐based estimates in CN (CSF 33%, PET 24%), SCD (CSF 36%, PET 27%), and MCI (CSF 60%, PET 49%), but comparable in CSF and PET in clinically diagnosed AD dementia (CSF 83%, PET 87) (Table 1, Figure 1).

Conclusion

We provide updated amyloid positivity estimates from the Amyloid Biomarker Study. CSF‐based estimates using a data‐driven approach resulted in higher estimates (up to 11% higher) in people without clinical AD dementia than PET‐based estimates. Whether CSF‐based estimates are more sensitive than PET‐based estimates for amyloid pathology among people without dementia needs to be explored in cohorts that use both modalities. These updated estimates may be useful to understand potential eligible patient population sizes for anti‐amyloid therapies and to inform recruitment strategies for clinical trials investigating anti‐amyloid therapies.
Physical activity and sedentary time in a multimodal lifestyle intervention in prodromal Alzheimer’s disease: The MIND‐ADMINI pilot trial
Authors: Thunborg Charlotta , Rosenberg Anna , Barbera Mariagnese , Coley Nicola , Ekblom Maria , Ekblom Örjan , Levak Nicholas , Solomon Alina , Kivipelto Miia
Published: December 2021

Background

Alzheimer’s disease (AD) is multifactorial. Interventions simultaneously targeting multiple risk factors are most likely to be effective, as demonstrated in the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). While patients with prodromal AD represent a group with high risk of progressing to dementia, no trials have tested the feasibility of multimodal interventions in prodromal AD. The main purpose of the MIND‐ADMINI was to evaluate the overall adherence to such multimodal intervention. This sub‐study focuses on exploratory outcomes which included physical performance and physical activity (PA) levels.

Method

MIND‐ADMINI is a 6‐month multicenter (Sweden, Finland, Germany, France) randomized controlled pilot trial. Participants with prodromal AD, between 60 and 85 years were randomized into three groups: usual care (control (C)), multidomain lifestyle intervention combining nutritional guidance, cognitive training, exercise, and careful monitoring of vascular risk factors (ML), or multidomain lifestyle intervention+medical food (ML+MF) (Fortasyn Connect). The multidomain lifestyle intervention was based on the FINGER model and included a progressive aerobic‐ and strength training program. Moderate to vigorous physical activity (MVPA), light activity, step counts, and time (min/day) spent sedentary were evaluated using data from a hip‐worn accelerometer. For each outcome, 6‐month values were regressed on baseline to estimate change.

Results

Baseline accelerometry data was available for 66 of 69 participants in Sweden, Finland, and France. At the 6‐month follow‐up, accelerometry data from 55 participants was included. At baseline mean age (SD) was 72,9 (6,2) years, 50,7% were men, and MMSE score was 27,6 (1,6) points. No significant values were found. At follow‐up, all groups increased their sedentary time, C (8,3%), ML (9,3%) and ML+MF (1,6%). Increased step count (3,4%) time in MVPA (2,8%) and light activity (9,5%) was observed during follow‐up in the ML+MF group.

Conclusions

Measurement of physical activity level using a hip‐worn accelerometer was feasible in this population. The observed increased time in MVPA, light activity and step counts in ML+MF group at the same time as sedentary time increased in all three groups between baseline and 6‐months follow‐up highlight the importance of physical activity as a part of multidomain lifestyle interventions in persons with prodromal AD.
Relationship between resting state alpha electroencephalographic rhythms and aging in cognitively unimpaired seniors and patients with mild cognitive impairment due to Alzheimer’s disease and amnestic mild cognitive impairment
Authors: Del Percio Claudio , Lizio Roberta , Noce Giuseppe , Lopez Susanna , Soricelli Andrea , Ferri Raffaele , Güntekin Bahar , Yener Gorsev , Marizzoni Moira , Frisoni Giovanni B , Babiloni Claudio
Published: December 2021

Background

The rsEEG alpha rhythms reflect cortical neural synchronization mechanisms underpinning the inhibition of sensory, cognitive, and motor areas in parietal, temporal, and occipital cortex during a condition of low vigilance. Here we tested the hypothesis that age may diversely affect rsEEG alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI).

Method

Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals ‐ matched as demography, education, and gender ‐ were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles).

Result

As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions (Figure 1 top). On the contrary, in relation to the younger ADMCI subgroups, the older one displayed lesser reduction in those rhythms (Figure 1 bottom). Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions as revealed by neuroimaging, and clinical and neuropsychological scores.

Conclusion

The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier vs. later onset of the AD.
Stress and Alzheimer’s disease: Linking salivary cortisol to biomarkers of neurodegeneration and cognitive decline in a memory clinic cohort
Authors: Daniilidou Makrina , Hagman Göran , Holleman Jasper , Sindi Shireen , Brinkmalm Ann , Zetterberg Henrik , Blennow Kaj , Solomon Alina , Sandebring‐Matton Anna , Kivipelto Miia
Published: December 2021

Background

Psychosocial stress has been shown to affect cognitive performance negatively and to increase the risk of developing dementia. Cortisol, a hormone thought to mediate several of the effects of chronic stress, has been shown to be elevated in Alzheimer’s disease (AD) patients. Interestingly, cortisol induces inflammatory responses that are detrimental to brain function. However, the relationship of this hormone with AD pathology, neuroinflammation, synaptic degeneration and neuronal survival is not well understood. The aim of this study is to investigate the interconnection of cortisol with CSF biomarkers of AD pathology, inflammation and synaptic dysfunction and with the serum neurotrophic factor BDNF and its precursor, proBDNF.

Method

Cross‐sectional analyses were performed on data from a total of 158 memory clinic patients with subjective cognitive decline (SCI, n=55), mild cognitive impairment (MCI, n=62) and Alzheimer’s disease (AD, n=41), from the Karolinska University Hospital in Sweden. Six timepoint diurnal salivary cortisol measurements, serum BDNF (both mBDNF and proBDNF) and the following CSF analytes were quantified: a neuroinflammation marker (chitinase‐3‐like protein 1 (YKL‐40)), markers of synaptic degeneration (synaptotagmin‐1, neurogranin and SNAP‐25) and AD pathology markers (Aβ1‐42, t‐tau and p‐tau). Linear regression models were performed for all participants and for each diagnostic subgroup, to examine the relationship between cortisol and the biomarkers, adjusting for age, sex, education and diagnosis. ANOVA, or Kruskal‐Wallis tests were applied to compare marker levels between the diagnostic groups.

Result

Positive associations were observed between salivary cortisol and CSF t‐tau, neurogranin and SNAP‐25. Salivary cortisol was also associated with lower peripheral proBDNF levels in the AD group. Increased awakening cortisol was associated with lower proBDNF levels in all participants, while a similar association could be observed for bedtime cortisol in the AD group only. There was no relationship between cortisol and YKL‐40, however YKL‐40 was associated with the synaptic markers. SNAP‐25 and neurogranin were higher in AD compared to SCI and MCI participants, confirming results from previous reports.

Conclusion

Our findings support an association of cortisol hypersecretion with neurodegeneration, synaptic dysfunction and the reduction of proBDNF in the periphery, which needs further investigation.
Demographics and clinical risk factor(s) variations in mortality of Alzheimer's disease in Taiwan: A 15‐year national population‐based study
Authors: Liu Chih‐Ching
Published: December 2021

Background

Identifying variation in the demographics and clinical risk factor(s) of the mortality for Alzheimer's disease (AD) has public health applications for projecting the future burden of disease. However, very few nationwide studies have been conducted on this topic in Asia countries. This study describes age‐, sex‐ and comorbidities‐ specific mortality in Taiwan as well as assesses the disparity of demographics and clinical factor(s) on the mortality of AD.

Method

This is a population‐based cohort study. The data of onset AD aged ≧40 years were acquired from the Taiwan National Health Insurance Research Database entries between 2000 and 2002.We used proportional hazards models to assess the effect of demographic and clinical factor(s) on 15 years of mortality after AD onset, Kaplan–Meier method for median survival times. We also further investigated survival time in incident AD by age‐, sex‐ and comorbidities‐stratified analyses.

Result

The median survival time during 15 years after first‐diagnosis of AD was 7.69 (95%CI :7.46‐7.90) years for overall, 6.37(95%CI :6.06‐6.65) years for men and 8.81(95%CI :8.49‐9.12) years for women. Predictors of mortality based on proportional hazards models included older age, males, and some specific clinical factors, including hypertension, diabetes mellitus, heart disease, and chronic obstruction pulmonary disease (COPD). Regardless of any gender, the survival time was shortest in subjects aged ≧80 years, especially in those with heart disease, diabetes mellitus, and COPD.

Conclusion

The significant demographics and clinical risk factor(s) variations in AD mortality. Public health interventions should consider these differences in health care resources.
Stimulation of cerebral angiogenesis and neurogenesis with transcatheter intracerebral laser photobiomodulation therapy during dementia in patients with Alzheimer's and Binswanger's disease
Authors: Maksimovich Ivan V
Published: December 2021

Background

The research investigates stimulation of cerebral angiogenesis and neurogenesis with Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) in patients with dementia with Alzheimer's disease (AD) and Binswanger's disease (BD).

Materials & Methods

Examined 120 patients suffering from dementia. Accomplished: CDR assessment, Tomography Dementia Rating scale (TDR), MMSE, cerebral CT, MRI, SG, rheoencephalography (REG), cerebral MUGA. We chose 48 patients suffering from AD aged 34‐80 (mean age 67.5), 17 men (35.42%) and 31 women (54.58%). The patients were subdivided according to dementia severity: preclinical stage (TDR‐0 dementia level) ‐ 4, mild stage (TDR‐1 dementia level) ‐ 16, moderately severe stage (TDR‐2 dementia level) ‐ 21, severe stage (TDR‐3 dementia level) ‐ 7 patients. 17 patients with BD aged 58‐81 (mean age 78) were selected, 11 men (64.71%) and 6 women (35.29%). According to dementia severity, the patients were subdivided: mild stage (dementia level CDR‐1) ‐ 9, moderately severe stage (dementia level CDR‐2) ‐ 5 patients. In hospital setting, all patients underwent Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT).

Results

All 48 (100%) patients with AD showed cerebral microcirculation improvement, as well as a 10‐20% increase in cerebral temporal lobes volume, which indicates cerebral neurogenesis development and tissue regeneration. The process was accompanied by dementia level decline and cognitive functions restoration. As a result, patients were transferred to the milder TDR stage group. Depending on the initial dementia severity, the obtained positive effect has been observed for 2‐10 years. All 17 (100%) patients with BD showed cerebral microcirculation improvement and cerebral involutional changes decline, which indicates neurogenesis development and tissue regeneration. The process was accompanied by dementia level decline and cognitive functions restoration. The resulting positive effect has been observed for over 10 years.

Conclusions

Despite the differences in the etiology of AD and BD, Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) is an effective treatment for dementia during these diseases. The method improves cerebral blood flow; it stimulates neurogenesis and tissue structure restoration, which lead to dementia decline and cognitive functions improvement. The resulting effect lasts for a long time.