bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of cognitive and fall risk associated with exercise in persons with Alzheimer’s disease
Authors: Carp Stephen John , Bartoli Elizabeth , Castro Marques , Heineman Matthew , Servin Rosalie , Spatola Giacomo
Published: June 2023

Background

The study aim was to elucidate the relationship between change in cognition and fall risk in persons with Alzheimer’s disease (AD) stratified for severity of illness and following a 10‐week exercise program. The authors hypothesize that a linear relationship exists between the severity of AD and decrease fall risk and severity of AD and improvement in cognition.

Method

Participants underwent a 10‐week exercise program designed to improve cognition and decrease fall risk. Cognition (Montreal Cognitive Assessment (MoCA)) and fall risk (Timed Up and Go (TUG)) were assessed prior to and after the exercise program. Normality was established for change in MoCA and change in TUG and for age of participants. RM‐MANOVA statistics were used to evaluate changes in the outcome measures prior to and after the exercise program. A post hoc Bonferroni evaluated differences between groups. The severity of AD was compared with change in cognition and fall risk outcome measures to determine if disease severity influenced cognition and fall risk with a 10‐week exercise program.

Results

The TUG analysis yielded two significant mean differences (p<0.05) between groups ‐ the mild/severe (p<0.001) and moderate/severe (p = 0.03) comparisons. However, there was no significant difference between the mild/moderate severity groups (p = 0.085). MoCA group differences comparison produced all statistically significant (p<0.001) mean differences, the largest occurring between the mild and severe groups. These data indicate a statistically significant relationship between severity of AD and change in TUG and MoCA scores following a ten‐week exercise program.

Conclusion

Persons with AD demonstrate impairments in cognition and fall risk leading to increased stress and costs. Exercise is an effective intervention for improving cognition and reducing fall risk in persons with AD. The relationship found between improvement of cognition and fall risk with exercise appears to be linear. The lesser severity of AD, the greater the cognitive and fall risk improvement. These data suggest that a 10‐week exercise program may improve cognition and decrease fall risk in persons with AD. The results from this study suggest that healthcare practitioners should consider early referral of persons with AD to group exercise programs to reduce the likelihood of falls and improve cognition.
The multifaceted impact of COVID‐19 on dementia caregivers
Authors: O'Connor Maureen K. , Shirk Steven , Moo Lauren R. , McLaren Jaye E. , Nguyen Andrew Huy , Pugh Kendra
Published: June 2023

Background

The COVID‐19 pandemic and consequent protective measures, including quarantines reduced or eliminated access to supports for dementia CGs. Dementia CGs have also reported increases in behavioral problems and decreases in cognition for the person with dementia (PWD) during the pandemic. We collected data on the impact of COVID‐19 on dementia CGs.

Method

CGs of PWD enrolled in a telehealth intervention were interviewed via video. At baseline, CGs completed The Caregiver COVID‐19 Limitations Scale. During interviews, CGs responses to questions about COVID‐19 related concerns and spontaneous discussion of concerns were recorded in field notes.

Result

Most CGs had a low level of concern that they would contract COVID‐19, but a slightly higher level of concern about the PWD. Several CGs reported at least a moderate impact of COVID‐19 related limitations on getting respite care (37.5%), leaving the house (50%), having outside visitors (25%), and gaining access to healthcare (25%). A quarter of CGs noticed at least a moderate change in the PWDs behavior. CGs also noticed cognitive decline. CGs felt changes were due to isolation, boredom, and depressive‐like symptoms. Caregivers also noted the loss of pleasurable activities they could engage in both alone and together with the PWD. A quarter of CGs also reported a great deal of difficulty explaining COVID‐19 related restrictions to the PWD. Specifically, memory loss experienced by the PWD necessitated frequent reminders about COVID‐19 and related limitation

Conclusion

Our results are consistent with literature demonstrating reduction in CG access to respite care and other supportive services during the pandemic. CGs noted declines in cognition and increases in neuropsychiatric symptoms in the PWD perceived to be due to isolation and lack of stimulation. CGs lacked access to previously enjoyable activities outside the home. CG noted the additional burden of lack of a shared pandemic experience due to memory loss that necessitated reminders about the pandemic and associated safety measures. In conclusion, dementia caregivers grapple with lost supports that increase burden, with simultaneously increases in perceived cognitive and behavioral problems in the PWD along with new pandemic‐specific burdens. Our findings underscore the necessity for increased dementia CG programming.
Elevated oxidative stress and inflammatory levels are associated with plasma AD biomarkers in middle‐age
Authors: Cherbuin Nicolas , Walsh Erin I. , Leach Liana , Bruestle Anne , Burns Richard , Anstey Kaarin J. , Sachdev Perminder S. , Baune Bernhard T
Published: June 2023

Background

Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer’s disease (AD). However, the extent to which inflammation is attributable to disease progression in the central nervous system in the pre‐ and clinical stages of dementia or emerges in the periphery and is a long‐term risk factor for the development of the pathological hallmarks of dementia is an unresolved question.

Method

Inflammatory (TNFa, TNF‐R1, TNF‐R2, IL1b, IL4, IL6, IL8, IL10), OS (NO, NEO, TAC), OS‐related DNA damage markers, and total tau, amyloid β1‐38 (Aβ38), amyloid β1‐40 (Aβ40), amyloid β1‐42 (Aβ42) levels were measured in plasma using highly sensitive immunoassays. Inflammatory and OS states were identified through principal component analysis. Associations between inflammatory/OS states and AD biomarkers were investigated in middle‐age (52‐56 years, n = 335, 52% female) and older‐age (72‐76 years, n = 351, 46% female) participants without dementia through linear regression analyses while controlling for relevant covariates.

Result

Four similar principal components reflecting different inflammatory states (PC1: unspecific increased inflammation; PC2: inflammation related to anti‐oxidant activity; PC3: increased OS activity with DNA damage; PC4: decreased OS and increased anti‐oxidant activity with DNA damage) were detected in the two age samples. In middle‐age, a component reflecting variation in OS (PC4) was most strongly associated with tau and to a lesser extent amyloid‐b levels. In older‐age, a similar component to that observed in middle‐age was only associated with tau, while another (PC1) component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers.

Conclusion

In middle and older age community‐living individuals without dementia inflammation and OS states are already associated with plasma AD biomarkers. The fact that more consistent and robust associations with AD biomarkers involved OS, or OS‐related DNA damage suggests that oxidative stress may be a particularly strong contributor to early AD pathophysiology and requires more systematic investigation.
Altered brain energy metabolism related to astrocytes in tauopathies
Authors: Hirata Kosei , Matsuoka Kiwamu , Tagai Kenji , Endo Hironobu , Kokubo Naomi , Tatebe Harutsugu , Zhang Hong , Shinotoh Hitoshi , Takahata Keisuke , Ono Maiko , Obata Takayuki , Kawamura Kazunori , Zhang Ming‐Rong , Shimada Hitoshi , Tokuda Takahiko , Yokota Takanori , Takado Yuhei , Higuchi Makoto
Published: June 2023

Background

Accumulated evidence suggests altered energy metabolism in the brain of tauopathies. In Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), decreased fluorodeoxyglucose (FDG) uptake in the cingulate cortex is considered a marker of neurodegeneration. However, its underlying pathogenesis remains unknown. It is hypothesized that lactate, a glucose metabolite, is produced in astrocytes and subsequently shuttles to neurons as an energy substrate. The current study aims to examine alterations in lactate and glucose concentrations and their association with astrocytic activities in the cingulate cortex of patients with AD and PSP.

Method

Thirty AD, 30 PSP, and 30 healthy control (HC) subjects were enrolled. Lactate, glucose, and myoinositol (mI), an astroglial marker, in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were determined by magnetic resonance spectroscopy (MRS) (3T scanner, SPECIAL sequence, TR/TE 3000/8.5ms, LCModel analysis) (Figure 1). Tau depositions were assessed using PET imaging with 18F‐PM‐PBB3.

Result

All the patients with AD and PSP were confirmed to have the typical distribution of tau pathology. Lactate, glucose, and mI levels were higher in the ACC in PSP and AD, and PCC in AD compared to HC (p < 0.05) (Figure 2). In these cortical regions, lactate levels showed a positive correlation with mI levels (p < 0.05) (Figure 3). Lactate levels in the PCC in AD patients showed a positive correlation with Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) scores (p < 0.05) (Figure 4). Moreover, mI levels in the ACC in PSP patients were negatively correlated with Frontal Assessment Battery (FAB) scores (p < 0.05) (Figure 4).

Conclusion

We found elevated lactate and glucose levels accompanied by an increased astroglial marker mainly in the PCC in AD and ACC in PSP patients. Moreover, elevated lactate and mI levels in the cingulate cortex reflected the cognitive decline of AD and PSP, respectively. The excess lactate and glucose levels in the disease‐specific regions might reflect decreased energy utilization as shown in previous FDG‐PET studies. Given the residual lactate levels were correlated with mI levels, we speculated that the impaired lactate shuttle of reactivated astrocytes disrupts energy metabolism, leading to cognitive dysfunctions.
Nanoscale‐alumina induced cognitive dysfunction in mice related to hippocampal structural changes: A stereological study
Authors: Naseh Maryam , Esmaili Zahra , Karimi Fatemeh , Moosavi Maryam
Published: June 2023

Background

Aluminum (Al) is known to induce neurotoxicity in both humans and rodents. Recent evidence has indicated that the toxicity of Al Oxide (Al2O3) Nanoparticles (Al‐NP), one of the most abundantly used engineered nanoparticles, is far greater than that of Al itself. To date, however, no information is available regarding the effect of Al‐NP on the stereological parameters of hippocampus. In particular, no stereological studies have evaluated the effect of Al‐NP on hippocampal CA1, dentate gyrus volume, and number of pyramidal and granular cells.

Method

Adult male NMRI mice were treated with AlNP in dose 10 mg/kg/oral gavage for 5 days. The test session of novel object recognition (NOR) task was performed on day 5. Following the NOR test, the hippocampi were analyzed for stereological and apoptotic.

Result

The results demonstrated that the five‐day Al‐NP ingestion elicited a reduced preference to explore a novel object in the novel object recognition test (a hippocampal‐dependent task). Perhaps contributing to this memory deficit, Al‐NP induced additional alterations in the hippocampus of male NMRI mice in terms of (1) hippocampal volume (decreased the volume of the whole hippocampus, CA1, and dentate gyrus regions), (2) cell number (decreased the number of CA1 pyramidal neurons and dentate gyrus granular cells), and (3) increased cleaved caspase‐3 in the whole hippocampus.

Conclusion

These results provided new mechanistic insight to understand the impairing effect of AL‐NP on the hippocampal function and structure.
Metamemory in older adults, preliminary results of a multifactorial training program
Authors: Feldberg Carolina , Natalia Irrazabal , Ofman Silvia Deborah , Hermida Paula Daniela , Tartaglini María Florencia , Somale Maria Veronica
Published: June 2023

Background

Cognitive intervention is a broad field that uses different means to increase or maintain these capacities. One of the aspects worked in memory training interventions refers to beliefs about performance, control and aging beliefs regarding this function in old age. More favorable beliefs towards memory in old age, performance capacity and greater self‐perceived control are related to successful aging and feelings of well‐being. The aim of the present study is to evaluate memory and aging beliefs in older adults who took part in a memory training program and a control group of subjects belonging to the same age group.

Method

Design: Comparative, pre‐post, longitudinal intervention study. Community dwelling older adults over 60 years. Memory training program participants (n = 58) (M = 70,04 years old; ds = 8.07 years) and controls (n = 72) (M = 69.92 years old; ds = 7.31 years) were assed at the begging and the end of the program. Instruments: Questionnaire of Social Demographic Data (built ad hoc), Brief Neuropsychological assessment for memory and attention. Metacognition: Memory Control Capacity Inventory (MCI) and ‐Metamemory Questionnaire. Procedure: All the participants of the Intervention group took part in the Memory training program. The program has a duration of 8 sessions of 90 minutes each, where theoretical and practical tools are provided to improve cognitive performance in everyday life Program participants and controls were assed twice, with eight weeks of difference between the first and second evaluation.

Result

Results reveal that when comparing the groups, statistically significant differences can be observed in favor of memory program participants in the following aspects: Metamemory beliefs: satisfaction(z = ‐3,376 p = .001), Metamemory capacity z = (‐2.32‐ p = .050) Metamemory Strategy (z = ‐4.556‐ p = .000), total metamemory beliefs (z = 4.620‐ p = .000) and in aging beliefs, in the aspect :aging independence concerns (z = ‐2.526 p = .000).

Conclusion

It is of great significance the incorporation of the assessment, training and observation of meta‐memory beliefs together with cognitive assessment and cognitive training in memory programs for older adults. The inclusion of cognitive training is an approach that can help cognitively vulnerable older adults and promote healthy cognitive aging.
Stigma and Dementia: an integrative systematic literature review
Authors: Abranches Iracema , Alves Larissa Scoralich , Santos Lucas Neves , Campos Samuel Cotrim Figueira Osorio , Saraiva Fernanda Bicalho , Benedicto Isabella de Paula Alves , Ferreira Ricardo Barbosa Leite Sérgio , Lima João Victor Semião , Lourenço Lelio Moura
Published: June 2023

Background

dementia can be defined as a clinical syndrome developed by pathological processes that affect cognitive functioning, which influences the individual’s way of perceiving and understanding the meaning of facts and feelings. Stigma is also a very broad concept, but it can be understood as negative attitudes and prejudices towards individuals who are perceived as different, whether because of a diagnosis, condition, or disease.

Method

an integrative systematic literature review was developed to analyze the relationship between stigma and dementia in order to give support to the research question. Drawing upon the Database of Descriptors in Health Sciences (Decs/Mesh), the following descriptors were applied: Estigma e demência (Port.), stigma and dementia (Eng.) estigma y demencia (Spa.). No result on the relationship between these descriptors were found at the Cochrane Library, which may confirm the originality of this review. As for the Open Access Documents, no date limit was applied. The databases used were BVS, PsycInfo, Pubmed, Scopus and Web of Science, following the PRISMA methodology.

Result

The initial search resulted in 8,127 titles; after the screening and exclusion criteria process, 42 articles were found for reading and categorization: 25 qualitative papers, 12 quantitative, 1 mixed quantitative and qualitative; 4 articles aimed at the validation and analysis of scales and intervention protocols. The articles mainly analyzed people with dementia, their caregivers, and families. All articles, empirical or theoretical, supported the correlation between stigma and dementia

Conclusion

the research outcome points out to the possible of analyze stigma in relation to dementia in different cultures, by applying different approach and methods, such as interviews, scales, questionnaires, and observation, among others. Stigma involves beliefs, attitudes, and behaviors which are susceptible to interventions that may improve public awareness of dementia. Further studies and intervention approach are needed to diminish stigma related to dementia.
Multiple target‐based combination therapy of galantamine, memantine and fisetin for the possible treatment of Alzheimer’s disease
Authors: Vishwas Sukriti
Published: June 2023

Dementia is defined by problems associated with memory, communication, problem‐solving, and other thinking abilities that impair a person’s capacity to carry out daily activities. Alzheimer’s disease is one of the them in which cognitive functions get declined. Globally, more than 44 million people are diagnosed with dementia till 2021. The Pathophysiology of Alzheimer’s disease is degeneration of acetylcholine neurons in the cerebral cortex and hippocampus parts of the brain, enhanced oxidative stress, neuroinflammation, mitochondrial dysfunction. Many clinical and preclinical studies have been reported on the treatment of AD but a very limited number of drugs have found a clinical application. Because regeneration of neurons is a complicated process due to the involvement of multiple pathways, a combination of drugs that can work through multiple pathways could prove to be effective in treating AD. Based on prior studies and different mechanisms involved in the treatment, a new hypothesis has been proposed that a combination of galantamine, memantine and fisetin is anticipated to produce better activity as compared to the current therapies available in market for the treatment of this disease.
Long‐term exposure to fine particulate matter is causally linked to increased risk of incident dementia among the American older adults: A national cohort study
Authors: Ma Tszshan , Wu Xiao , Schwartz Joel , Yitshak‐Sade Maayan , Steenland Kyle , Chang Howard H , Shi Liuhua
Published: June 2023

Background

Growing studies link long‐term fine particle (PM2.5) exposures to increased risk of Alzheimer’s disease and related dementias (ADRD), but these findings have been disputed citing traditional approaches do not guarantee evidence of causality.

Method

We constructed two national U.S. population‐based cohorts of enrollees aged ≥65 from the Medicare Chronic Conditions Warehouse (2000‐2018), combined with high‐resolution air pollution datasets, to estimate the effect of long‐term exposure to PM2.5 on dementia and AD incidence, respectively. We applied multiple distinct causal inference approaches, i.e., under a set of causal inference assumptions, to compare the health estimates. We first considered three causal inference modelling approaches that rely on the potential outcomes framework and generalized propensity scores (GPS). These approaches adjust for measured confounding using 1) matching by GPS; 2) weighting by GPS; and 3) including GPS as a covariate in the health outcome model. Then we further applied the difference‐in‐differences approach that controls for unmeasured confounders by design to add robustness to any causal conclusions.

Result

For the period 2000‐2018, we found that all statistical approaches provide consistent results, suggesting that long‐term exposure to PM2.5 is causally linked to increased incidence of ADRD.

Conclusion

Using a large nationwide cohort and robust epidemiologic analyses, we provide strong evidence of the causal link between long‐term PM2.5 exposure and increased incidence of dementia and AD. Our results support the importance of continued assessment the impact of air pollution exposure on neurological disorders among the older adults.
Calcium Triggered Compound Fusion at Ribbon Synapses During Exocytosis
Authors: Jamal Armaan , Markert Sebastian , Watanabe Shigeki
Published: June 2023

Background

Exocytosis in photoreceptors involves fusion of vesicles with the plasma membrane at the base of a specialized proteinaceous electron‐dense structure known as a synaptic ribbon. The molecular mechanisms underlying exocytosis at ribbon synapses are not well understood. Research suggests a compound fusion model where vesicles at ribbon synapses undergo homotypic fusion forming larger vesicles prior to fusion with the plasma membrane. But how this process is mediated remains unclear. Ca2+ triggers several forms of exocytosis in different types of eukaryotic cells through activation of the SNARE complex. SNARE‐mediated fusion of membranes is triggered by the calcium sensor Synaptotagmin, but not much is known about whether this applies to compound fusion. Here, we report that, like typical synaptic exocytosis, compound fusion is mediated by Ca2+ influx.

Method

To examine the role of calcium in compound fusion, we performed vesicle purification experiments from Mus musculus (C57BL/6 WT) retina. Brain tissue was also used as a control where we expected no compound fusion. Retina and brain tissue were dissected, homogenized, and ultracentrifuged. The supernatant was incubated in 2mM Ca2+ for 5 minutes then vesicles from the Ca2+samples and controls containing no Ca2 were isolated using magnetic beads coupled with rho1D4 monoclonal antibody. Vesicles were negatively stained and viewed under TEM. Vesicle sizes of the Ca2+ and control samples were determined via blind analysis using ImageJ.

Results

In retina samples, exogenous Ca2+ caused a significant increase in vesicle size when viewed under TEM. In the retina Ca2+ samples, vesicle diameter ranged from 30nm to 250nm. This effect was not seen in retina controls where vesicle diameter ranged from 30nm to 60nm. No large vesicles were seen in any of the brain samples.

Conclusion

Our research supports the compound fusion model of vesicle exocytosis at ribbon synapses. We suggest that in retina, the larger vesicles formed during exocytosis are a result of smaller vesicles fusing with each other and that Ca2+ has a significant role in this process. Future studies investigating the role of calcium sensors such as synaptotagmin will help to further elucidate the mechanisms underlying compound fusion and its therapeutic potential in neurological disorders.
Association of physical activity, brain volume, and plasma biomarkers of Alzheimer’s disease: The Shanghai Aging Study
Authors: Wu Wanqing , Xiao Zhenxu , Liang Xiaoniu , Zhao Qianhua , Ding Ding
Published: June 2023

Background

This study aimed to explore the potential relationship between physical activity and brain volume as well as plasma biomarkers of Alzheimer’s disease in the Chinese population.

Method

This cross‐sectional analysis included 99 dementia‐free community‐dwelling older adults from the Shanghai Aging Study. Physical activity was assessed based on questionnaires and further transformed into metabolic equivalent values (MET‐hours). Older adults were then divided into two groups: low physical activity (≤21.0 MET‐hours) and high physical activity (>21.0 MET‐hours), based on the median of MET‐hours. Data on age, sex, years of education, and smoking status were collected through questionnaires. DNA was extracted from the blood or saliva samples to conduct apolipoprotein E (APOE) genotyping. Histories of hypertension and diabetes were confirmed by the medical records. Voxel‐based morphometry analysis was performed to quantify brain volumes. Hippocampal volume estimates were obtained using the free surfer image analysis suite. Plasma β amyloidAβ40, Aβ42, Tau, and neurofilament light (Nfl) were measured by the single‐molecule array. Multivariate linear models were used to examine the association between physical activity, brain volumes, and plasma biomarkers.

Result

We observed a significant inverse association between physical activity and the level of plasma Aβ40 (high vs. low physical activity, β = ‐17.883, r = ‐0.222, p = 0.039) and a marginally significant association between physical activity and the level of plasma Aβ42 (high vs. low physical activity, β = ‐1.394, r = ‐0.204, p = 0.058), after adjusting for age, sex, years of education, APOE ε4, smoking, hypertension, and diabetes. Physical activity displayed no significant associations with plasma Tau, Nfl as well as brain volumes.

Conclusion

The protective effect of physical activity on cognition might rely on its effect on the β amyloid burden.
Measuring olfactory‐related brain region volume loss in MCI and AD using structural MRI
Authors: AlOtaibi Majed , De Marco Matteo , Venneri Annalena
Published: June 2023

Background

Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Olfactory dysfunction can be an early alteration heralding the presence of AD. Studying the pattern of alterations in olfaction‐related brain regions might help detection of neurodegenerative diseases at an earlier stage. Objectives of this study are to assess the volume of olfactory areas associated with odour processing in healthy elderly, MCI and AD populations using structural MRI scans. To test whether there are any differences in the volume of olfactory related regions between patients and healthy controls. To determine whether there is an effect of sex on olfactory‐related brain regions’ volume loss.

Method

Neurologically healthy participants aged 66‐85 (n = 95), MCI aged 58‐86 (n = 81) and mild probable AD aged 55‐88 (n = 37) participants were recruited. T1‐ weighted MRI scans acquired at 1.5T were processed using SPM12. Smoothed images were used to extract the volume of olfactory cortex, hippocampus, parahippocampus, amygdala, orbitofrontal cortex and entorhinal cortex.

Result

One‐way ANOVA analyses showed a significant reduction in all olfaction‐related brain regions (p≤0.0001). Post‐hoc multiple comparison tests showed a significant reduction in volume in the AD group in all olfaction‐related brain regions. In the MCI group, a significantly smaller volume than the healthy controls was found in four of the selected olfactory‐related brain regions (namely, hippocampus, parahippocampus, amygdala and entorhinal cortex) for the total and left volume in the female group only. Additionally in the female MCI, the volume of the right entorhinal cortex however, was also significantly smaller than that of the control group. When adjusting for MMSE, however, between group differences in all olfaction‐related brain regions were no longer significant.

Conclusion

These preliminary data show a significant reduction in grey matter volume in all olfaction‐related brain regions. Grey matter volume loss in these regions appears to be a good proxy of disease severity.
Impact of MCI on testing performance in different cognitive domains
Authors: Shi Xiangrong , Reddy Priyanka M , Abdali Kulsum , Ross Sarah E , Davis Sandra , Hall James , Mallet Robert T
Published: June 2023

Background

Impaired memory affects cognitive testing performance. This study examined in elderly adults the impact of mild cognitive impairment (MCI) on testing performance in different cognitive domains.

Method

After giving their IRB‐approved written consent, 10 cognitively normal subjects (65±2 years old) and 10 patients with amnestic MCI (68±2 years old) completed the Mini‐Mental State Examination (MMSE), Digit‐Span test, California Verbal Leaning Test –2nd edition (CVLT‐II), and Trail Making Test – B version (TMT‐B). Cognitive performances of the MCI and normal groups were compared by standard t tests. ANOVA was applied to evaluate the impacts of the group and trial‐number factors on immediate Free‐Recall (FR) performance in CVLT‐II.

Result

The group MMSE scores were 24.8±0.4 in the MCI group vs 29.2±0.3 in the normal subjects (P<0.0001). The time to complete TMT‐B was prolonged markedly in the MCI (154±28 s) vs. normal (56±6 s) subjects (P = 0.007). Forward performance score in the Digit‐Span test did not differ between the groups (MCI 9.0±0.6 vs normal 8.5±0.9), although backward Digit‐Span performance was superior (P = 0.021) in the normal (7.0±0.6) vs. MCI (5.1±0.4) groups. CVLT‐II immediate FR scores improved with successive trials in both MCI and normal subjects (trial‐number factor P<0.0001). Although the FR scores from the first 2 trials did not differ between the groups, there was a significant difference appeared in the FR scores of the 3rd and the overall FR scores were appreciably lower in the MCI subjects (group factor P = 0.006). Moreover, 30‐sec Short‐Delay (S‐D) and 10‐min Long‐Delay (L‐D) FR scores were significantly lower in the MCI subjects (Table).

Conclusion

Both short‐term memory and visuospatial‐executive function were significantly impaired in the MCI patients as compared with the age‐matched cognitively normal cohort. Repeated trials improve the immediate Free‐Recall in both groups. The backward Digit‐Span test was more sensitive than the forward test to detect the impairment of short‐term memory and attention in the elderly adults with MCI.
Independent contribution of ATN biomarkers for progression of amnestic mild cognitive impairment to AD on top of neuropsychological tests
Authors: Zhao Lei , Shi Lin , Luo Yishan , Mok Vincent C.T. ,   for the Alzheimer Disease Neuroimaging Initiative
Published: June 2023

Background

ATN biomarkers (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) have been known for their predictive value of Alzheimer’s disease (AD). Here, we aimed to investigate their independent contributions to predicting progression of amnestic mild cognitive impairment (aMCI) to AD on top of neuropsychological tests.

Method

We included 496 aMCI patients with neuropsychological tests and ATN biomarkers from cerebrospinal fluid (CSF) examinations, MRI and FDG‐PET at baseline. The involved ATN biomarkers included CSF‐Aβ, CSF‐Ptau, CSF‐Tau, FDG‐PET and an MRI‐based Alzheimer’s disease resemblance atrophy index (AD‐RAI) calculated by AccuBrain IV2.0. All the demographic and neuropsychological features (Table 1) were entered into the cox model with backward elimination to predict time to AD (subscores of FAQ and ADAS‐cog also entered as candidate predictors) using training cohort (n = 330, 34.8% developed AD within 3.60±2.46 years). The resulting model was treated as the basic model. The enriched models with individual and multiple ATN biomarkers were further compared with the basic model regarding the improvement in C‐index (measuring prediction performance of time to AD) and time‐dependent AUC (t‐AUC, measuring prediction performance of time‐specific progression) in validation cohort (n = 166, 35.5% developed AD within 3.66±2.52 years).

Result

The features that survived backward elimination for the basic model were shown in Table 2. Binary form of A/T/N variables were preferred for Aβ/Tau, while continuous form preferred for Ptau/FDG‐PET/AD‐RAI (Table 3). Compared with the basic model, all the enriched models with individual A/T/N biomarkers (except for Basic+Tau) presented higher C‐index in the training cohort (p<0.05), while only Basic+(AD‐RAI) and Basic+(FDG‐PET) presented higher C‐index in the validation cohort (Table 4). Basic+(FDG‐PET) presented highest t‐AUC (0.861∼0.924) among the models with individual A/T/N biomarkers (Figure 1A). The enriched model with multiple ATN biomarkers (Aβ/Ptau/FDG‐PET/AD‐RAI) presented highest C‐index in both training and validation cohort, which also showed higher t‐AUCs (generally ≥0.90 through year 3∼7) than the models with individual A/T/N biomarkers in trend (Figure 1B). These findings indicated that multiple ATN biomarkers should be used for the optimal model (Figure 2).

Conclusion

ATN biomarkers, when combined in use, presented most contribution to predicting aMCI‐to‐AD progression independent of demographic characteristics and neuropsychological tests.
How white matter hyperintensities impacts Alzheimer’s disease and frontotemporal dementia across underrepresented Latin American samples
Authors: Campo Cecilia Gonzalez , Fraile‐Vazquez Matias , Ibanez Agustin
Published: June 2023

Background

White matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer’s disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD.

Method

A total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined.

Result

Total and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum‐hippocampus bundle in AD.

Conclusion

Enhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain‐specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age‐related increase in WMH.
Structural integrity of the anterior mid‐cingulate cortex contributes to resilience to delirium in SuperAging
Authors: Wong Bonnie , Katsumi Yuta , Cavallari Michele , Fong Tamara G. , Alsop David C , Andreano Joseph M , Carvalho Nicole , Brickhouse Michael , Jones Richard N , Libermann Towia A , Marcantonio Edward R , Schmitt Eva M , Shafi Mouhsin , Pascual‐Leone Alvaro , Travison Thomas G , Barrett Lisa F , Inouye Sharon K. , Dickerson Brad C. , Touroutoglou Alexandra
Published: June 2023

Background

Identifying factors that confer resilience to developing delirium is critical given the negative impact of delirium on clinical care and risk for mortality. Here, we investigated a cohort of cognitively normal older adults undergoing elective surgery and examined the role of pre‐operative memory function and cortical thickness in the incidence and severity of post‐operative delirium (POD). We hypothesized that 1) those older adults with episodic memory function comparable to that of young adults (“SuperAgers" or SA) would show reduced incidence of POD compared with typically‐aging older adults (TOA) and 2) cortical thickness in the anterior mid‐cingulate cortex (aMCC), the integrity of which has been consistently associated with SuperAging, would predict reduced incidence and severity of POD.

Method

19 SA and 74 TOA (mean age 75.8 +/‐ 4.1; 57F/36M) completed neuropsychological testing and underwent structural brain MRI pre‐operatively as part of the Successful AGing after Elective Surgery (SAGES) Study. SA were identified based on neuropsychological criteria defined in previous studies. Delirium incidence and severity were assessed using the Confusion Assessment Method (CAM) daily throughout hospitalization. A general linear model analysis was performed to identify regions of the cerebral cortex whose thickness was associated with CAM scores.

Results

No differences were found in age or education between SA and TOA. Remarkably, no SA developed POD; POD occurred only in the TOA group (D‐TOA = 15). Severity of POD was negatively associated with cortical thickness of bilateral aMCC. A one‐way ANOVA comparing mean aMCC thickness across subgroups revealed a significant effect (F(2,89) = 3.09, p ≤ .05), with thickness greatest in SA compared with D‐TOA (t(31) = 2.47, p ≤ .019, Cohen’s d = 0.89), but comparable compared to thickness seen in non‐delirious (ND) TOA (t(76) = 0.72, p ≤ .72, d = 0.10). Greater aMCC thickness was also observed for ND‐TOAs compared with D‐TOAs (t(71) = 2.26, p ≤ .03 d = 0.72).

Conclusion

These findings suggest that superior memory function and greater structural integrity of the aMCC may be important indices of resilience to delirium in older adults that can serve as a target of preventive or therapeutic interventions.
Development of an app‐based life story intervention: Lessons learned from including persons living with dementia in focus group research
Authors: Wilk Christa , Cordell Ashlee , Orsulic‐Jeras Silvia , Powers Sara , Ejaz Farida , Sanders Beth
Published: June 2023

Background

A small‐scale focus group study was conducted utilizing persons living with dementia (PLWD) to inform the development of an app‐based life story review intervention.

Method

Two (Time 1 and Time 2) 60‐minute virtual (Zoom) focus groups were conducted 9 months apart with persons living with dementia (n = 5) and facilitated by research staff. In Time 1, participants were sent in advance a series of LifeBio MemoryTM tablet‐app prototypes and asked to provide specific feedback on the following: 1) ease of use, 2) clarity of instructions, 3) feasibility to use the product, and 4) potential impact on person‐centered care practices. Time 2 presented the complete app to participants for similar feedback. To maximize successful participation, participants received one‐on‐one support by research staff prior to focus groups. Assistance was provided with using Zoom and navigating the tablet and LifeBio MemoryTM prototype and app. Dementia‐friendly materials were created for participants. Research staff conducted a thematic analysis of all transcripts. Time 1 findings were utilized to inform product development based on PLWD‐specific feedback; Time 2 findings were utilized for product refinement.

Result

Although the PLWD sample was small, promising acceptability and feasibility findings were reported. All 5 PLWD participated in Time 1 and Time 2 focus groups. Themes from Time 1 (prototype) findings included: 1) Comfort using app‐based product technology, 2) Value of sharing their life story, 3) Training issues, 4) Implementation concerns, and 5) Concerns with how PLWD are perceived. PLWD feedback, was integrated in the development of the product. Analysis of Time 2 determined: 1) Some remaining training concerns, 2) High levels of satisfaction, and 3) Buy‐in that a product like LifeBio MemoryTM can impact person‐centered care. Themes, recommendations, and action steps were proposed and changes were made in content and functionality, in preparation for an upcoming feasibility study to test the LifeBio MemoryTM app with PLWDs living in residential care (n = 242).

Conclusion

By building in supports, persons living with dementia are able to successfully participate as members of a research team, providing valuable feedback as stakeholders in product development research; further, virtual delivery of focus groups is also possible.
Asian Americans and Pacific Islanders’ preferences in recruitment strategies/messaging for participation in a research recruitment registry for Alzheimer’s disease and related dementias, aging, and caregiving research: A discrete choice experiment survey
Authors: Park Van Ta , Grill Joshua D. , Ameli Niloufar , Helman Sarit , Tzuang Marian , Tsoh Janice Y. , Meyer Oanh L. , Nam Bora , Hinton Ladson , Kanaya Alka , Gallagher‐Thompson Dolores , Vuong Quyen , Bang Joon , Shin Hye‐Won , Gansky Stuart
Published: June 2023

Background

Underrepresentation of Asian Americans and Pacific Islanders (AAPIs) in research requires urgent attention. The Collaborative Approach for AAPIs Research and Education (CARE) registry aims to increase AAPIs’ representation in research. We report results from a multilingual discrete choice experiment (DCE), an innovative method to determine older AAPIs’ preferences for tailored recruitment strategies and messaging.

Methods

Initial DCE recruitment strategy/messaging attributes and attribute levels were selected based on feedback from CARE focus groups. A pilot study (16 participants from 7 AAPI cultural groups) refined attribute wording and levels. The final DCE survey was translated into Simplified and Traditional Chinese, Korean, and Vietnamese. CARE academic and community partners recruited participants (AAPIs aged ≥50 years) for the survey, asking them to select their preference in each of 12 pairs of recruitment strategies (randomly selected from 48 different combinations) of three attributes: (1) from whom they would like to learn about CARE; (2) what would motivate them to join CARE; and (3) how they would prefer hearing about CARE. A custom Qualtrics survey displayed image pairs of randomly selected messaging combinations. Analyses utilized conditional logistic regression models to estimate odds ratios with 95% confidence intervals.

Results

A total of 356 (mean age = 65.0; range: 50‐93) participants from 7 AAPI cultural groups (Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, and Vietnamese) completed the survey. Overall, participants had similar preferences for learning about CARE between community organizations and the healthcare community, however, participants preferred learning about CARE from the healthcare community (e.g., doctors, clinics) relative to community champions and faith‐based organizations. Participants were more motivated to join CARE to help advance research relative to sharing personal experiences; and preferred to hear about CARE via social media and instant messaging relative to a flyer or workshop/seminar. Importantly, preferences varied by age, cultural group, survey completion language, and whether the participant received assistance with the survey.

Conclusions

To our knowledge, this is the first study using a DCE approach to elicit preferences for registry recruitment strategies among AAPIs. Findings will inform appropriate tailoring of recruitment strategies/messaging to successfully engage AAPI participants in a registry for ADRD research.

aging after age 90.
Association of motor function with cognitive trajectories, risk of mild cognitive impairment, and structural brain differences
Authors: Wang Zhangyu , Yang Wenzhe , Li Xuerui , Dove Abigail , Qi Xiuying , Bennett David A , Xu Weili
Published: June 2023

Background

The impact of motor function (MF) on cognitive trajectories and mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association of MF with cognitive trajectories, risk of MCI, and structural brain differences on magnetic resonance imaging (MRI).

Method

Within the Rush Memory and Aging Project, 1,216 cognitively intact participants (mean age: 78.60±7.25 years) were followed for up to 22 years. Baseline global MF was assessed by averaging the z‐scores of 10 motor tests and categorizing these scores tertiles (low middle, and high). Global and domain‐specific cognitive functions – including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed – were assessed annually through 19 cognitive tests. Incident MCI was detected and diagnosed based on standard criteria. A subsample (n = 284) underwent brain MRI and regional structural brain volumes were measured. Data were analyzed using linear mixed‐effects models, Cox regression, and linear regression.

Result

At baseline, global MF scores ranged from 0.46 to 1.82 (mean score: 1.06 ± 0.22). During the follow‐up (median, 6.98 years; interquartile range, 3.08‐10.75 years), 553 participants (45.48%) developed MCI. Compared to participants with high MF, those with low MF had faster decline in global cognition (β = ‐0.05, 95% confidence interval [CI]: ‐0.06 to ‐0.03), episodic memory (β = ‐0.05, 95% CI: ‐0.07 to ‐0.03), semantic memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.02), working memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.03), visuospatial ability (β = ‐0.03, 95% CI: ‐0.04 to ‐0.02), and perceptual speed (β = ‐0.04, 95% CI: ‐0.06 to ‐0.03) over the follow‐up. The multi‐adjusted hazard ratio (95% CI) of MCI was 1.84 (1.41 to 2.42) for the lowest MF tertile compared to the highest. Furthermore, the low MF was related to a significantly greater volume of white matter hyperintensities (β = 0.16, 95% CI: 0.01 to 0.32), but not total brain, white matter, or gray matter volumes (all P >0.05).

Conclusion

Low MF is associated with faster cognitive decline (including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed) and a moderately increased risk of MCI. Vascular pathologies might play an important role in the MF‐MCI association.