bluuebunny/crossref_metadata_2025 huggingface dataset:
Fat and the brain: its connection and implication in AD pathogenesis
Authors: Bettinetti‐Luque Miriam , Trujillo‐Estrada Laura , Andreo‐Lopez Juana , Cantero‐Molina Francisco , Da Cunha Celia , Sanchez‐Mejias Elisabeth , LaFerla Frank , Gutierrez Antonia , Baglietto‐Vargas David
Published: June 2023

Background

Alzheimer’s disease (AD) is a complex disorder and multiple cellular and molecular mechanisms are involved in AD onset and progression. Recent evidences has suggested that metabolic alterations are an important pathological feature in disease progression in AD. Likewise, diabetes and obesity, two mayor metabolic illnesses, are risk factors for AD. These two overwhelming diseases are associated with a significant expansion of white adipose tissue. Here, we hypothesize that the white adipose tissue may serve as a key communicator organ between the brain and peripheral metabolic illnesses and affecting both types of disorders.

Method

We used histological stains, immunohistochemistry and biochemical means to determine changes in the white adipose tissue from WT and db/db mice. Moreover, similar techniques were used in the brain of 3xTg‐AD mice that received white fat pads from WT and db/db donors to determine any changes in amyloid and tau pathology.

Result

Our study shows that recipient 3xTg‐AD mice from db/db fat pads mice develop profound changes in tau pathology due to increased CDK5 expression compared to 3xTg‐AD mice that received fad pads from WT mice. This increment in tau level was associated with elevated levels in IL‐1β and profound microglia activation. Moreover, we found the opposite effect on amyloid pathology, in which insoluble Aβ levels and Thioflavin positive plaques were reduced in recipient 3xTg‐AD mice from db/db fat pads compared to 3xTg‐AD mice that received fad pads from WT mice. These reduction in Aβ levels were correlated with an increment in microglia phagocytic capacity.

Conclusion

Overall, our study demonstrate a novel important crosstalk between Alzheimer´s disease and diabetes type II through white adipose cells and a differential effect on tau and Aβ pathology mediated by an activated immune response.
Cognitive resilience and severe Alzheimer’s disease neuropathology: role of smoking
Authors: Ahangari Narges , Fischer Corinne E. , Schweizer Tom A. , Munoz David G.
Published: June 2023

Background

Why some individuals with significant Alzheimer’s disease(AD) lesions in their brain retain their cognitive abilities while others with the same level of pathology manifest symptoms of dementia remains incompletely understood. The term cognitive resilience refers to this phenomenon. With limited success in pharmacological interventions that prevent the onset of AD pathology, more efforts are aiming toward developing strategies to delay the clinical expression of AD; acetylcholinesterase inhibitors serve as an example, and compounds with similar pharmacodynamics such as nicotine may play a similar role. Here we sought to identify demographic, clinical, genetic, and neuropathological features associated with cognitive resilience in participants with severe AD neuropathology.

Method

Data for this retrospective cohort was collected from the datasets developed by the National Alzheimer’s Coordinating Centre (NACC). Individuals with severe AD pathology and no other primary neuropathology diagnoses who had their last visit within 2 years of their time of death were included. Severe AD pathology definition was based on National Institute on Aging–Reagan (NIA‐Reagan) criteria pathology, i.e., frequent neuritic plaques and Braak & Braak stage V/VI pathology. Cognition was assessed using the Mini‐Mental Status Examination (MMSE) score at their last visit and cases with scores ≥24 were defined as being cognitively intact, and thus resilient. Following bivariate analysis to compare resilient with non‐resilient groups, significantly different variables were adjusted for demographics using logistic regression analysis. Subsequently, statistically significant characteristics were entered in a multivariable model.

Results

We classified 59(9%) individuals as resilient and 595(91%) as non‐resilient. The binary logistic regression model showed that resilient subjects were older (odds ratio[OR] = 1.03;95% confidence interval[CI] = 1–1.07), had more years of education (OR = 1.16;95%CI = 1.04‐1.29), had lower BMI (OR = 0.91;95%CI = 0.85‐0.99), were more likely to be a smoker (OR = 2.78;95% CI = 1.45‐5.34), and were more likely to use an anticoagulant/antiplatelet at last visit compared with subjects with impaired cognition (OR = 1.87;95%CI = 1.01‐3.48).

Conclusions

Our results corroborated previous findings that lower BMI and higher education are associated with AD cognitive resilience, and additionally demonstrated that the level of smoking and usage of anticoagulant/antiplatelet medication have a direct relationship with cognitive resilience to AD severe pathology. Nicotine mimetics could be explored as a potential option for preventing AD clinical expression.
Reconfigured metabolism brain network in asymptomatic microtubule‐associated protein tau mutation carriers: A graph‐theoretical analysis
Authors: Liu Li , Chu Min , Xie Kexin , Cui Yue , Rosa‐Neto Pedro , Chen Kewei
Published: June 2023

Background

Studies exploring topologic properties of the metabolic network in the presymptomatic stage of genetic frontotemporal dementia (FTD) are scarce, which may be important for understanding brain function and disease pathogenesis. This study aimed to explore FTD‐specific patterns of metabolism topology reconfiguration in asymptomatic microtubule‐associated protein tau (MAPT) mutation carriers.

Method

Six asymptomatic carriers of MAPT P301L mutation were compared with 12 non‐carriers who were all from the same large family of FTD. For comparison, we included 32 behavioral‐variant FTD (bvFTD) patients and 33 unrelated healthy controls. Each participant underwent neuropsychological assessments, genetic testing, and hybrid PET/MRI scan. Voxel‐wise gray matter volume and standardized uptake value ratio were calculated and compared for structural MRI and FDG‐PET, separately. The sparse inverse covariance estimation (SICE) method was applied to topologic properties and metabolic connectomes of brain functional networks derived from 18F‐fluorodeoxyglucose PET/MRI data. Independent component analysis was used to explore metabolic connectivity in the salience (SN) and default mode networks (DMN).

Result

The mean estimated years from symptom onset was 8.33 ± 1.875 years in the mutation carrier group. The asymptomatic MAPT carriers show no significant differences in cognitive tests, gray matter volume and FDG uptake compared to non‐carriers. They also retained normal global parameters of metabolism network, but not for bvFTD patients. However, we revealed lost hubs in the ventromedial prefrontal, orbitofrontal, and anterior cingulate cortices and reconfigured hubs in the anterior insula, precuneus, and posterior cingulate cortex in asymptomatic carriers, which is consistent with the findings in bvFTD patients. Similarly, significant differences in local parameters of these nodes were observed in asymptomatic carriers. The reduction in connectivity was marked in lost hub regions during the asymptomatic stage. Functional connectivity within the SN and DMN was enhanced in asymptomatic carriers, while reduced in bvFTD patients.

Conclusion

Our findings showed that asymptomatic MAPT carriers were initially involved in medial prefrontal areas and actively compensated in task‐related regions. Topologic properties of the metabolic network may contribute to further investigations and monitoring of the earliest stages of FTD in individuals with genetic backgrounds.
Genome‐Wide Association Study for CSF Aβ42, Tau, and pTau in a Large Multi‐cohort Study to Identify Novel AD Genetic Variants
Authors: Gomez‐Fonseca Duber
Published: June 2023

Background

Previous studies have identified more than 20 genetic loci to be associated with AD risk. These reported loci do not account for all the estimated heritability nor report enough information on the undelaying biological mechanism. Genome‐wide association studies of endophenotypes have identified new loci associated with Alzheimer’s disease. To better understand AD pathology and identify new variants implicated in AD much larger samples size is needed. We conducted a GWAS of Amyloid‐beta (Aβ42) tau, and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) to detect novel variants associated with AD.

Methods

AD CSF biomarkers were measured in 7282 individuals from 24 different cohorts. Samples were genotyped using different array technology with stringent quality control standards to each dataset before combining datasets. Minimum call rate for single nucleotide polymorphism (SNP) and individuals was 99.85%. SNPs not in Hardy–Weinberg equilibrium were excluded. X‐chromosome SNPs were analyzed to verify sex identification. Duplicates and cryptic relatedness among samples were tested by pairwise genome‐wide estimates of proportion identity‐by‐descent. PLINK was used to calculate principal component analysis. CSF biomarker levels were log10‐transformed to approximate a normal distribution with the mean standardized to zero for each dataset to account for the variability on the different platforms used to measure proteins levels. One‐stage joint‐GWAS to maximize the power in our analysis. Post‐GWAS analyses Colocalization, Madelian Randomization, LD Score Regression, were implemented to detect colocalization of two potential related signals to detect common causal variant and to evaluate the overlap in genetic architecture of CSF Biomarkers and risk factor for AD

Results

This study represents one of the largest multi‐cohort GWAS analyses on CSF AD biomarkers. Several genome‐wide significant hits were found including APOE. Additional analyses are underway.

Conclusions

CSF Aβ42, tau, and ptau are well established AD endophenotypes with a clear genetic association with APOE genotype and AD risk. Genetic studies on endophenotypes provide enough power to detect association with a smaller sample size than case‐control studies helping us to better understand the biological mechanism of the disease. With this study we aim to identify novel variants implicated in AD.
Inflammasome Activation after Traumatic Brain Injury as a Risk Factor for Alzheimer’s Disease
Authors: Johnson Nathan H , Kerr Nadine A , Vaccari Juan Pablo de Rivero , Bramlett Helen M , Keane Robert W , Dietrich W Dalton
Published: June 2023

Background

Traumatic Brain Injury (TBI) is a major cause of death and disability in the United States and a recognized risk factor for the development of Alzheimer’s disease (AD). Recent studies identified that heightened inflammasome signaling plays a critical role in the pathogenesis of CNS injury and that the release of apoptosis ‐associated speck‐like protein containing a caspase recruitment domain (ASC) specks from neurons and activated microglia contributes significantly to the detrimental innate immune inflammatory response. This study investigated whether inflammasome signaling after TBI augmented AD‐induced biochemical and neuropathological outcomes and loss of cognitive functionality using established AD‐transgenic mouse models.

Method

Five‐month‐old, 3xTg mice (with expressed APPswe, PS1M146V and tauP301L genes) and wild type controls were randomized and underwent moderate TBI controlled cortical impact (CCI) injury or served as controls. Animals were allowed to recover for 1 hour, 1 day, or 1 week after TBI (n = 5‐8/group) to assess acute pathology or were allowed to recover for 12 weeks (n = 10/group) in order to assess cognitive functionality and chronic pathology. At the end of the respective recovery periods, mice were sacrificed. The ipsilateral cortex tissue was processed for inflammasome protein expression by immunoblotting analysis. The chronic group was assessed for behavior utilizing open field (3 days), novel object recognition (2 weeks), and Morris water maze (6 weeks) testing after TBI.

Result

There was a statistically significant increase in the expression of inflammasome signaling proteins Caspase‐1, Caspase‐8, ASC, and IL‐1β in controls and TBI in both wild type and transgenic animals. Importantly, at 1 day after TBI, significant increases in ASC, Caspase‐8 and IL‐1β protein expression were observed in AD mice compared to wild type. In the chronic group, behavioral testing showed that injured mice had increased cognitive loss as indicated by decreased time in the center of the open field, and decreased time investigating the novel object.

Conclusion

These findings show that the inflammasome is involved in the regulation of the innate immune response after TBI in AD‐transgenic mice and that TBI acts as a potential accelerant of AD pathology.
Prevalence of dementia and cognitive impairment no dementia in a large nationally representative sample: The ELSI‐Brazil study
Authors: Bertola Laiss , Suemoto Claudia Kimie , Aliberti Marlon Juliano Romero , Gonçalves Natalia G , Pinho Pedro José M. R. , Lima‐Costa Maria Fernanda , Ferri Cleusa P
Published: June 2023

Background

Approximately 77% of older adults in Brazil with dementia have not been diagnosed, indicating a major public health issue. Previous dementia epidemiologic studies from Brazil were based on data from one geopolitical region. We aimed to estimate the general and subgroup‐specific (age, education, and sex) prevalence of dementia diagnosis and cognitive impairment no dementia (CIND) using data from 5,249 participants aged 60 years and older from the Brazilian Longitudinal Study of Aging (ELSI‐Brazil), a large nationally representative sample of older adults.

Method

Participants were classified as either: having normal cognitive function, CIND, or dementia based on a combination of the individuals’ cognitive and functional status. A normative subsample provided adjusted regression‐based norms for the cognitive assessment, and a z‐score of ‐1.5 or lower for global cognition was considered to indicate cognitive impairment. We considered functional impairment if the participant reported one or more difficulties in four gender‐independent daily living activities. Participants were classified as having normal cognitive function if there was no cognitive and functional impairment, as CIND if there was only cognitive impairment, and as dementia if there were both cognitive and functional deficits or if the informant scored above 3.4 points in the Informant Questionnaire on Cognitive Decline in the Elderly.

Result

We found a general prevalence of 6.1% (95% CI = 5.1‐7.3) for dementia and 8.6% (95% CI = 7.1‐10.3) for CIND (Table 1). Dementia prevalence ranged from 3.3% (60‐64 years) to 43.0% (≥ 90 years) by age, and from 2.0% (College level or higher) to 17.5% (illiterates) by educational level. Females had a higher prevalence (7.4%) than males (4.4%). CIND prevalence was similar across the age, sex, and education groups.

Conclusion

The estimated dementia prevalence is in line with previous epidemiologic studies. Only 0.8% of the ELSI participants self‐reported having a previous diagnosis of dementia, revealing that underdiagnosis is rampant and a common reality. Based on our results, we expect that nearly 1.7 million of the 2015 population, and 2 million of the 2019 population, might have dementia in Brazil.
BENEFICIAL EFFECTS OF PROTEIN RESTRICTION ON METABOLIC HEALTH, COGNITIVE FUNCTION AND NEUROPATHOLOGY IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Authors: Lamming Dudley , Babygirija Reji , Calubag Mariah , Sonsella Michelle , Murphy Michaela , Pak Heidi , Yeh Yang , Flores Victoria , Green Cara , Matouska Ryan , Michael John , Tobon Anna , Lab Lamming
Published: June 2023

Background

Age is the greatest risk factor in developing Alzheimer’s Disease (AD); hence, there is great interest in the possibility of targeting AD through interventions that slow or delay aging. Dietary protein restriction (PR) has been shown to be beneficial in improving overall healthspan in both humans and mice. However, the effect of PR in delaying the symptom progression of AD is largely unknown. In this study, we sought to determine the effects of PR in improving metabolic dysfunction, cognitive deficits and AD pathology along with examining the role of mTORC1 and its downstream targets in the 3xTg mouse model of AD.

Method

Six month old male and female 3xTg‐AD mice were placed on either 21% protein (control) or 7% protein (PR) diets starting from 6 months and continued until 15 months to determine their effects on cognition, metabolic health and AD neuropathology. Cognitive functioning was assessed via Novel Object Recognition (NOR) test and Barnes maze test.

Result

Female 3xTg‐AD mice on PR diet showed improved long‐term memory (LTM), and males showed a positive trend in improved cognitive function compared with their age matched controls. Based on latency measurements in Barnes maze, we found that a PR diet substantially improved spatial memory in both male and female 3xTg mice. Female and male mice on low protein diets exhibited improvement in glucose tolerance, however females showed a stronger effect in glycemic control than males following a glucose tolerance test (GTT). Histopathological analysis of the hallmarks of AD showed that mice on PR had decreased tau phosphorylation and Aß plaques. Phosphorylation of the mTORC1 substrate S6K1 was decreased in PR fed 3xTg mice which suggest that reduced mTORC1 signaling may be mediating the beneficial effects of PR on AD pathology. We also found that levels of p62 protein, the major autophagy cargo receptor, is increased in 3xTg AD mice and following PR, decreased p62 expression was observed, suggesting that PR activates autophagy.

Conclusion

These results suggests the molecular interplay between mTORC1 and autophagy in PR mediated beneficial effects in diminishing AD pathology.
Endogenous hormones in mid‐life and later‐life subjective memory impairment in women
Authors: Sharma Sneha , Clendenen Tess V , Wu Fen , Afanasyeva Yelena , Koenig Karen L , Zeleniuch‐Jacquotte Anne , Chen Yu
Published: June 2023

Background

Reproductive hormones may impact cognition in women. Recent literature suggests that subjective memory complaints (SMCs) can be an early indicator of cognitive impairment. However, epidemiologic data are mixed, with few prospective studies exploring endogenous sex hormones in relation to later‐life SMCs. Assessing this potential association may elucidate an etiology of risk for cognitive impairment in women.

Method

We included 616 premenopausal and 102 postmenopausal women from the New York University Women’s Health Study (NYUWHS), a prospective cohort study with blood samples collected at enrollment (1985‐91) and over 35 years of follow‐up to collect health and lifestyle information. Women were ineligible for inclusion in the cohort if they used hormone medications or were pregnant 6 months prior to enrollment. Healthy controls from prior NYUWHS case‐control studies were eligible for participation in this study if their baseline blood sample had already been used to measure circulating hormones, and they responded to at least one of two follow‐up questionnaires (2018‐present) featuring 6 questions about SMCs. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of baseline hormones with subsequent SMCs, adjusting for age, race, education, original case‐control study, and body mass index (BMI) in a separate model.

Result

Androstenedione, testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone binding globulin (SHBG) were measured in samples collected at baseline for pre‐ and post‐menopausal women; estradiol and estrone were also measured in postmenopausal women. There were no significant associations between premenopausal circulating hormones or SHBG and SMCs. Postmenopausal hormones were inversely associated with SMCs, including in age and BMI‐adjusted models: ORs (95% CIs) for SMCs associated with doubling in testosterone and estradiol were 0.58 (0.35‐0.95) and 0.39 (0.17‐0.90), respectively.

Conclusion

Higher postmenopausal concentrations of testosterone and estradiol are inversely associated with risk of later‐life SMCs in women.
The association between MIND diet and cognitive function among Chinese middle aged and older adults: A 9‐year longitudinal study
Authors: Huang Liyan , Tao Yang , Chen Hui , Chen Xiao , Shen Jie , Zhao Caifeng , He Mengjie , Zhu Dafang , Yang Ming , Zhang Ronghua , Yuan Changzheng
Published: June 2023

Background

Evidence on the association of Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function is limited. This study examined how MIND diet is related to cognitive function among Chinese middle aged and older adults.

Method

This longitudinal study comprised 4066 participants aged ≥55 years from the China Health and Nutrition Survey in 1997. Dietary assessment (using 3‐day 24‐hour dietary recalls) and cognitive tests (using modified Telephone Interview for Cognitive Status) were conducted repeatedly from 1997 to 2006. The study MIND diet score was calculated based on 9 healthy food groups and 3 unhealthy food groups. Linear mixed‐effects models were used to investigate the relation of MIND diet adherence to cognitive function (z‐score).

Result

The median MIND score was 4.5 (range: 0‐12) among overall participants at baseline. During a mean follow‐up of 5.9 years, participants with higher scores of MIND diet had significant better global cognitive function in subsequent years. In the multivariable‐adjusted model, the regression coefficients (95% CI) across the tertiles of MIND score were 0 (ref), 0.01 (‐0.03, 0.06), and 0.07 (0.02, 0.11), respectively. For dietary components, highest consumption (T3 vs T1) of nuts (β = 0.24, 95% CI: 0.09, 0.38), fish (β = 0.11, 95% CI: 0.05, 0.16), poultry (β = 0.09, 95% CI: 0.03, 0.16), red meat (β = 0.09, 95% CI: 0.05, 0.14), tea (β = 0.08, 95% CI: 0.03, 0.13), and green leafy vegetable (β = 0.04, 95% CI: ‐0.00, 0.09) were associated with better global cognitive function, whereas highest intake of fried food (β = ‐0.18, 95% CI: ‐0.26, ‐0.10), pastries and sweets (β = ‐0.07, 95% CI: ‐0.16, 0.02) demonstrated opposite associations. Furthermore, the beneficial association of MIND diet with cognitive function was stronger among residents in rural areas, soutern areas, and among illiterate participants though significant effect modifications were not observed.

Conclusion

Our findings suggest that higher adherence to MIND diet was associated with better cognitive function in later life. Further research is warranted to confirm the findings and to investigate the underlying mechanisms.
Canonical correlation analysis of hippocampus and basal forebrain cholinergic brain structures with cognitive domain‐specific performance scores
Authors: Ardekani Babak , Zaborszky Laszlo
Published: June 2023

Background

Hippocampal atrophy is a diagnostic marker of AD and various compartments of the basal forebrain cholinergic (BFC) system also show volume reductions that correlate with cortical thinning and volume reduction in their innervated targets in the hippocampus. Moreover, bilateral volume loss of the nucleus basalis Meynert (Ch4) and spreading the atrophy to medial septum and vertical limb of the diagonal band of Broca (Ch12) in preclinical and prodromal AD show correlation with abnormal CSF levels of Aβ1‐42 and phosphorylated tau. It is unclear, however, how volume integrity of hippocampus and various compartments of the cholinergic space (Ch12 and Ch4) associate with specific cognitive domains.

Method

Data from 402 participants were downloaded from the AD Neuroimaging Initiative [120 AD, 118 cognitively normal (CN), and 164 mild cognitive impairment (MCI)]. For each participant, domain‐specific performance scores were downloaded for: memory (ADNI‐MEM), executive function (ADNI‐EF), language (ADNI‐LAN) and visuo‐spatial ability (ADNI‐VS). In addition, all participants had 3D T1‐weighted structural MRI scans (3T) from which we computed the structural integrity measures for the left and right hippocampus (LHC, RHC), Ch4 (LCH4, RCH4) and Ch12 (LCH12, RCH12) BFC nuclei. Canonical correlation analysis (CCA) was used to determine the association between the 4 cognitive measures on the one hand and the 6 brain structural MRI measures on the other hand after controlling for age and sex.

Result

The first and second canonical correlation coefficients were found to be statistically significant: r1 = .56 (p<.001) and r2 = .23 (p = .011). The first pair of canonical correlation vectors (CCVs), indicated that predominantly ADNI‐MEM (Fig. 1) is associate with a bilateral hippocampal integrity (LHC and RHC) (Fig. 2) particularly on the right. Moreover, the corresponding cognitive and structural canonical variates differentiated between CN, MCI and AD (Fig. 3). The second pair of CCVs indicated that predominately ADNI‐LAN (Fig. 4) was associated with RHC>LHC asymmetry (Fig. 5). However, the corresponding canonical variates did not differentiate between groups (Fig. 6).

Conclusion

Bilateral hippocampal atrophy is associated with reduced ADNI‐MEM performance, and both differentiate CN, MCI and AD. Asymmetry of the hippocampal volumetric integrity is associated with ADNI‐LAN (LZ was supported by NIH RF1NS023945‐28).
Peripheral transport proteins were associated with 4‐year cognitive decline in APOE ε4 non‐carriers: A longitudinal, population‐based study
Authors: Gao Ling , Qu Qiumin
Published: June 2023

Background

Soluble low‐density lipoprotein receptor‐related protein‐1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid‐β (Aβ).We aim to determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association.

Method

Cognitively normal subjects were followed‐up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini‐Mental State Examination (MMSE), and cognitive decline was defined as a ≥2‐point decrease of MMSE after 4‐years. The association between baseline sLRP1/sRAGE and 4‐year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship.

Result

769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4‐year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13‐3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ε4 non‐carriers (adjusted OR = 1.60, 95% CI: 1.04‐2.48, p = 0.034).

Conclusion

Individuals with lower levels of sRAGE had an increased risk of 4‐year cognitive decline in APOE ε4 non‐carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.
Cognitive function and its influencing factors in chinese with advanced age: An observational study based on comprehensive geriatric assessment
Authors: Chen Lihua , Liu Bei , Liu Xingtong , Zhang Mengtong , Lü Yang
Published: June 2023

Background

Cognitive impairment is an age‐related clinical problem that has a significant negative impact on the quality of life of elderly individuals. Hence, it is necessary to identify and intervene the factors affecting cognitive impairment early. Comprehensive geriatric assessment (CGA) is a multidimensional, multidisciplinary diagnostic and therapeutic process used to evaluated the medical, psychosocial, and functional abilities of older adults. This study aimed to evaluated the cognitive function and to explored the risk factors in the old elderly in Chongqing, southwest China by analyzing the CGA assessment data.

Method

A cross‐sectional study was conducted in 551 inpatients aged 80 years or older of Department of Geriatrics in The First Affiliated Hospital of Chongqing Medical University from July 2017 to August 2018. Participants were measured with CGA to assess the physical condition, cognition, mental health status, fatigue, nutrition, and presence of geriatric syndromes. Cognitive function was assessed with the Mini‐Mental State Examination (MMSE). The factors associated with cognitive function were analyzed with independent sample t‐test, chi‐square test, and rank‐sum test. The relationship between cognitive impairment and risk factors was examined with logistic regression analysis.

Result

Among the 551 subjects, 313 (56.8%) had different degrees of cognitive impairment. The cognition function was obviously correlated with literacy (z = ‐3.294,P< 0.001), diabetes (x² = 6.862,P< 0.009), nutrition (z = ‐3.466, P<0.001), GDS‐5 (x² = 25.955, P<0.000). Furthermore, logistic regression analysis showed that age (odds ratio (OR) = 1.117, 95% confidence interval (CI): 1.1048–1.190), no diabetes (OR = 0.628, 95% CI:0.400–0.984), normal GDS‐5 (OR = 2.417, 95%CI: 1.568–3.000), and malnourished (OR = 2.481, 95%CI:1.159–5.313) were significantly associated with cognitive function.

Conclusion

Our results suggest that age, poor literacy, diabetes, depression and malnutrition are significantly associated with an increased risk of cognitive impairment. Therefore, improving nutritional status, controlling blood glucose and regulating emotions have positive regulatory effects on cognitive function of the older elderly.
Neuropsychiatric symptoms in Amnestic Mild Cognitive Impairment: Mexican clinical and community based‐study
Authors: Alarcón Edgar Iván Jiménez , Acosta‐Castillo Gilberto Isaac , Ibarrola Mariana Longoria , Sosa‐Ortiz Ana Luisa
Published: June 2023

Background

The neuropsychiatric symptoms (NPS) are common clinical manifestation in older adults with amnestic mild cognitive impairment (aMCI). Global prevalence of 35%‐85% is estimated, though there are inconsistencies across the studies. There are reports of its prevalence in clinical and community‐based studies but few comparisons between them.

Methods

Restrospective and cross‐sectional study design. A total of 86 patients with amnestic MCI, aged 65 years or older were included. Of these, 27 were a tertiary hospital clinical sample and 59 from a population‐based study, from the 10/66 Dementia Research Group protocols. We described and compared sociodemographic, comorbidity and neuropsychiatric symptoms data, last ones measured by the Neuropsychiatric Inventory Questionnaire (NPI‐Q). Aim was to compare the frequency of NPS, its severity and caregiver distress between samples.

Results

The most frecuent NPS in both populations were depression, anxiety and irritability with no differences between samples. Apathy was more prevalent in clinical sample versus community‐based (33.3% vs 8.47%, p: 0.009). The most severe NPS were anxiety, nightime behaviors and delusions with no differences among samples. Appetite/eating disorders had a moderate to severe caregiver distress but no differences were found.

Conclusion

The results of this study are consistent with the international literature as depression been the most frecuente NPS in aMCI. Only apathy was found more prevalent in clinical community but no relation with higher severity and caregiver distress.
Pre‐stroke chronic cerebrovascular disease is a major determinant for response to structured cognitive rehabilitation following acute ischemic strokes
Authors: Leow Yi Jin , Saffari Seyed Ehsan , Chua Esther Vanessa , Mei Nyu Mei , Baharudin Nur Nazaria , Wong Fennie , Ng Sheng Chun , Ng Kok Pin , Kandiah Nagaendran
Published: June 2023

Background

Post Stroke Cognitive Impairment (PSCI) is seen in 40‐60% of patients with ischemic strokes. Response of patients with PSCI to structured cognitive rehabilitation is not clearly understood. We evaluated baseline variables that predict response to an eight‐week non‐pharmacological intervention among patients with mild strokes and compared the responses to non‐pharmacological intervention among acute stroke patients with and without chronic cerebrovascular disease (CVD).

Method

139 ischemic stroke survivors were recruited from a tertiary hospital in Singapore. All patients underwent an eight‐week structured group cognitive rehabilitation programme (Figure 1). Baseline, immediate post‐intervention (Immediate‐PI) and 6‐month post intervention (6‐month‐PI) global cognitive and quality of life (QOL) outcomes were assessed by Montreal Cognitive Assessment (MoCA) and Dementia‐Quality of Life (DemQOL). Regression analyses evaluated the influence of cognitive rehabilitation on outcomes.

Result

The mean age of subjects were 63.6 (±9.66) with 64.4% males. Baseline MoCA and DemQOL scores were 23.30 (±3.05) and 79.16 (±14.80). At Immediate‐PI, patients with more past strokes (p = 0.033) and severe white matter hyperintensities (WMH) (p = 0.048), benefited less on global cognitive outcome (Table 1). Male patients (p = 0.074) and patients with more severe WMH (p = 0.048) benefited less on QOL outcome (Table 2). At 6‐month‐PI, patients with microhemorrhages in the deep region (p = 0.002) were less likely to sustain cognitive improvement. With every past stroke experienced, patients were less likely to experience an improvement in MoCA score Immediate‐PI (OR = 2.17, 95% CI: 0.980‐4.813, p = 0.056). with severe WMH were less likely to experience an improvement in MoCA scores Immediate‐PI compared to baseline (OR = 2.13, 95% CI: 1.04‐4.38, p = 0.039). Finally, patients with microhemorrhages in the deep region were less likely to retain the improvements in MoCA at 6‐month‐PI (OR = 19.93, 95% CI: 1.04‐384, p = 0.047)

Conclusion

Pre‐stroke CVD were associated with worse cognitive and QoL outcomes post cognitive rehabilitation. Understanding factors that result in poor response to rehabilitation will allow clinicians to better select stroke survivors for cognitive rehabilitation. Future research could build on these findings and allocate more resources to these at‐risk groups for post‐stroke care, therefore reducing the global burden of stroke and ensuring a better QOL for stroke survivors.
Dysphagia, mealtime behaviors, and eating ability of persons living with dementia: A systematic review of psychometric properties of instruments
Authors: Kim Sohyun , Lee Kyuri , Mann Madison , Liu Wen
Published: June 2023

Background

It is critical to use validated instruments to assess dysphagia, mealtime behaviors, and eating ability of persons living with dementia to evaluate the efficacy of mealtime care interventions. However, the characteristics and psychometric quality of such instruments are unknown. This systematic review aims to synthesize the quantity and quality of instruments that assess dysphagia, mealtime behaviors, and eating ability of persons living with dementia.

Method

We searched Pubmed, CINAHL, AgeLine, PsychINFO, and Cochrane Library for records published from January 1980 to July 30th, 2021. Records were eligible if they included any instrument that measures concepts of interest (i.e., dysphagia, mealtime behaviors, eating ability). Instruments were excluded if they assessed nutritional status only. Eligible instruments originally developed or later modified to measure concepts of interest were identified from eligible records. Eight characteristics of eligible instruments will be extracted: 1) development process, 2) concept/construct being operationalized, 3) sample and setting, 4) administration method, 5) description of items, 6) scoring format/interpretation, 7) reliability, and 8) validity. The Psychometric Assessment for Self‐report and Observational Tools (PAT), a newly developed psychometric quality assessment tool, will be used to evaluate the psychometric quality of eligible instruments.

Result

In total, 11,074 records were reviewed. Seventy‐nine eligible instruments were identified from 174 records. Fifteen instruments assessed swallowing ability; 5 assessed mastication ability; 6 assessed dysphagia; 24 assessed mealtime behaviors; 7 assessed eating ability; 22 assessed two or more concepts of interest.

Conclusion

A large number of instruments were developed and/or used to assess dysphagia, mealtime behaviors, and eating ability of persons living with dementia. All instruments’ psychometric properties will be further evaluated to inform the application and adaption of appropriate instruments for practice and research.
Utility of linguistic biomarkers for prediction of cognitive impairment and limbic predominant age related TDP‐43 neuropathologic change in the oldest old
Authors: Bubbico Giovanna , Akhlaghipour Golnoush , Khan Zainab , El‐Khoury Annelisse , Corrada María M. M. , Kawas Claudia H. , Paganini‐Hill Annlia , Sajjadi S. Ahmad
Published: June 2023

Background

There is an urgent need for accessible biomarkers that can predict cognitive impairment in older individuals. There is also a complete lack of biomarkers for TAR DNA‐binding protein‐43 (TDP‐43), a frequent and important neurodegenerative pathology in older individuals, currently referred to as Limbic‐predominant Age‐related TDP‐43 Encephalopathy‐Neuropathologic Change (LATE‐NC). Here we explored the utility of linguistic markers for prediction of future cognitive impairments and LATE‐NC.

Method

134 participants of the Leisure World cohort, an epidemiologic study in a California retirement community, produced written descriptions of the cookie‐theft picture from the Boston Aphasia Diagnostic Examination. All had normal cognition at the time. Samples were quantitatively analyzed for 31 linguistic markers (see table 1 for definitions of select relevant variables). Participants subsequently joined the 90+ study and underwent cognitive assessments every 6 months and autopsy after death. Cognitive impairment and its onset date were determined at postmortem conferences. LATE‐NC was considered present in those with TDP‐43 in hippocampus or neocortex, and Alzheimer’s disease neuropathologic change (ADNC) in those with high likelihood ADNC according to NIA‐ AA guidelines. To examine the relationships between linguistic markers and future cognitive impairment and presence of LATE‐NC and ADNC, we used logistic regression analysis. Models were adjusted for sex, education, age at the time of writing the samples and age at death.

Result

Table 2 summarizes demographic and neuropathology findings. Additionally, mean age at cognitive impairment was 93.2 in 72% who developed cognitive impairment. Future cognitive impairment was significantly associated with less information content (OR:0.02) and fewer clauses (OR:0.93) (Table 3). Also, presence of LATE‐NC was significantly associated with higher proportions of content words (OR:7.2), higher proportion of function word errors (OR:10.5), and fewer complete units (OR:0.15). Lower number of words also trended towards a significant association (OR:8, p = 0.07) with LATE‐NC. No language measure was associated with ADNC.

Conclusion

Our results suggest that linguistic markers derived from writing samples obtained on average 8 years prior to development of cognitive impairment and 12 years before death might serve as biomarkers for future cognitive impairment and presence of LATE‐NC at autopsy.
Importance of promoting trauma‐informed dementia therapies in a pandemic World: Building on person‐centered practices
Authors: Ione Adrienne
Published: June 2023

For people living with Alzheimer’s disease and related dementias (ADRD), who are ages 65 and greater, and who are living in a COVID‐19 era have been labeled the most vulnerable among us. And yet, the pandemic holds a unique opportunity for members of this subgroup of our global population, to interact with stress in a previously unimagined way, thereby highlighting the importance of adopting trauma‐informed therapies. Although it is anticipated that 152.8 million people will be living with dementia by 2050, the pandemic is presenting a real opportunity to turn the tide. Although the bulk of research on delivering trauma‐informed yoga therapies has focused on veterans and people experiencing PTSD, this research makes a strong case for policy implementation of a systematic trauma‐informed yoga therapy program to be delivered to people living with dementia. Further, it has been suggested that participation in a 3‐month yoga and meditation program can prevent dementia development. Given the appropriate support systems, the stresses of COVID‐19 can support healthy neuronal rewiring. Stress augments the plasticity capacity of the brain’s structural and functional mechanisms. It is imperative however that within this proposed model of dementia therapy, for stress to be monitored by a trained trauma‐informed therapist to the extent that practices are not retraumatizing. For people living with ADRD, having their stresses individually dosed in a way to facilitate memory growth, thereby increasing one’s healthspan, is possible so long as stress hormones are maintained at a moderate level so as to facilitate, rather than suppress memory.
Results of a low cost dance intervention for cognitive reablement in dementia
Authors: Shah Ayushi , Bergman Nate
Published: June 2023

Background

, dance therapy may offer a solution to reduce morbidity, restore aspects of cognitive ability (even if only temporarily), and potentially reduce the total cost of care to individuals and the health care system. But more reliable data on the effectiveness of dance therapy within the dementia community is needed

Method

Four female participants with severe major neurocognitive disorders and loss of Activities of Daily Living (ADL) function were included. Participants were selected by the facility’s life enrichment director based on their likelihood to consistently participate in the dance intervention. Loss of ADL function was confirmed by chart review in the facility’s electronic medical record monthly functional tracking summaries. The dance intervention was done for 30 minutes three days a week for four weeks. Though not by design, Participant 4 chose not to dance and served as a tacit “control” in our review. Popular music from the 1950s, country music, and/or Christmas music was played for the duration of each dance session. The participants were evaluated by an MMSE at the beginning of the month before starting the intervention and immediately following after the final dance session.

Result

Average Change in MMSE: 3.375 points. Participant 4 decreased in MMSE score, and participant 1,2, and 3 all improved

Conclusion

our intervention demonstrates the feasibility of dance therapy as a potentially effective, low‐cost cognitive reablement strategy that may improve function in those already suffering with dementia and loss of independence. Future studies should be prospectively designed, ideally contain a control group, and be statistically powered to explore the role of frequency, intensity, and duration on outcomes.
Using the Driving and Dementia Roadmap (DDR) to address the emotional impact of driving cessation and dementia
Authors: Naglie Gary , Stasiulis Elaine , Sandhu Harvir , Gallucci Christina E. , Rapoport Mark J.
Published: June 2023

Background

The emotional impact of driving cessation for people living with dementia (PWD) and their family/friend carers (FCs) can be significant, often contributing to their avoidance of this issue. In addition to the grief and anger associated with PWD’s loss of identity and independence, feelings of fear and distress can accompany PWD’s and FC’s lack of knowledge about driving cessation. In this study, we conducted an implementation evaluation of the Driving and Dementia Roadmap (DDR). The DDR is a web‐based collection of resources and tools to support PWD and FCs through the decision‐making process and transition to non‐driving, including information on managing the oft‐neglected emotional implications of stopping to drive.

Method

Semi‐structured interviews were conducted with 19 Alzheimer Society (AS) staff after a three to six month period of delivering the DDR to their clients in six AS sites in four Canadian provinces. Eight PWD and 13 FCs who engaged with the DDR were also interviewed. Participants were asked about their experiences of delivering or using the DDR. An inductive thematic analysis of the data was conducted.

Result

According to study participants, the DDR had both a direct and indirect impact on the emotional aspects of driving cessation for FCs and PWD. FCs described how the emotion content gave them insight about the grief and loss the PWD was experiencing. This understanding helped them to attend to the emotional ramifications of driving cessation and to initiate conversations about driving with compassion, empathy and patience. Indirectly, the DDR also helped PWD and FCs feel that they are not alone, thus “normalizing” driving cessation. They reported being reassured that the actions they had taken and decisions made to stop driving were appropriate. Strategies about remaining mobile also brought relief and hope that PWDs’ quality of life could be maintained once driving ceased.

Conclusion

By providing resources and tools that not only directly address the emotional impact of driving cessation, but also attend to other aspects of managing the decision‐making and transition to non‐driving, the DDR has the potential to lessen the associated grief, fear and distress often experienced by PWD and FCs.
Pathways to diagnosis: The lived experiences of obtaining a dementia diagnosis among care partners
Authors: Xu Hanzhang , Fish Laura J , Nohria Raman , Christy Jacob , Falkovic Margaret , Dupre Matthew E. , Anderson Ruth , Ostbye Truls
Published: June 2023

Background

Achieving a timely diagnosis of Alzheimer’s disease and related dementias (ADRD) has been challenging, and racial/ethnic minority older adults often have delays in their ADRD diagnoses despite having a higher disease prevalence. This qualitative study engaged care‐partners of patients to identify key barriers that they have experienced during their ADRD diagnosis process, ascertain their recommendations for addressing these barriers, and assess racial differences in the diagnosis process.

Method

We purposively sampled 11 Black and 10 White care‐partners (n = 21) of persons who were diagnosed with ADRD within the past two years. We conducted semi‐structured interviews to gather details and to identify the barriers/facilitators that they experienced. To prompt discussion, we asked participants to complete a card sort activity identifying occurrence and order of common events in the diagnosis pathway. We applied content analysis guided by life course theory to identify themes and to explore differences in diagnosis pathways between Black and White participants.

Result

Overall, about 70% of care‐partners were female, age 60 (on average), and 57% were adult children of persons with ADRD. Less than 30% of Black care‐partners reported having adequate knowledge about ADRD, whereas the proportion was 60% among their White counterparts. Most often, early signs of ADRD were first noticed by care‐partners. However, some considered these signs as part of the normal aging process. Care‐partners reported visiting multiple providers along the process, and some visits were related to other conditions. Some care‐partners noted that the involvement of other family members was a barrier to the ADRD diagnosis. Most care‐partners described the diagnosis process as difficult and devastating, and Black care‐partners discussed experiencing unmet needs along the process more frequently than White care partners. Some care‐partners suggested having a navigator that can walk them through the process would be helpful. They also shared that the navigator should be able to tailor services based on the needs, as each family’s situation is different.

Conclusion

This study highlights the unmet needs experienced by care partners along the diagnosis process of ADRD. Black and White differences were also identified. More person‐centered care coordination programs are needed to promote early identification of ADRD.