Journal of Alzheimer's Disease Reports - Volume 8, issue 1

Authors: Moon, Sung Seek | Anderson, Lindsey | Liu, Jinyu | Lee, Jinwon | Moon, Youngkwang

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) poses a growing public health challenge, particularly with an aging population. While extensive research has explored the relationships between AD, socio-demographic factors, and cardiovascular risk factors, a notable gap exists in understanding these connections within the Asian American elderly population. Objective: This study aims to address this gap by employing the Classification and Regression Tree (CART) approach to investigate the intricate interplay of socio-demographic variables, cardiovascular risk factors, sleep patterns, prior antidepressant use, and AD among Asian American elders. Methods: Data from the 2017 Uniform Data Set, provided by the National Alzheimer’s …Coordinating Center, were analyzed, focusing on a sample of Asian American elders (n  = 4,343). The analysis utilized the Classification and Regression Tree (CART) approach. Results: CART analysis identified critical factors, including levels of independence, specific age thresholds (73.5 and 84.5 years), apnea, antidepressant use, and body mass index, as significantly associated with AD risk. Conclusions: These findings have far-reaching implications for future research, particularly in examining the roles of gender, cultural nuances, socio-demographic factors, and cardiovascular risk elements in AD within the Asian American elderly population. Such insights can inform tailored interventions, improved healthcare access, and culturally sensitive policies to address the complex challenges posed by AD in this community. Show more

Keywords: Alzheimer’s disease, Asian American, classification and regression tree, National Alzheimer’s Coordinating Center

DOI: 10.3233/ADR-230162

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 517-530, 2024

Authors: Pruitt, Patrick J. | Damoiseaux, Jessica S. | Hampstead, Benjamin M. | Peltier, Scott J. | Bhaumik, Arijit K. | Albin, Roger L. | Dodge, Hiroko H.

Article Type: Research Article

Abstract: Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. Methods: 112 older adults (70.7±7.3 years, range 54.6–89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer’s Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) …cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults. Show more

Keywords: Alzheimer’s disease, cognitive aging, functional connectivity, older adults, salience network, social engagement

DOI: 10.3233/ADR-220082

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 531-542, 2024

Authors: Tsatali, Marianna | Moraitou, Despina | Gialaouzidis, Moses | Bakoglidou, Evaggelia | Psaltis, Vasilis | Bertzes, Natalia | Hassanin, Hany Ibrahim | Emmanouilidou, Eudokia | Totonidis, Michael | Frantzi, Nikoleta | Avdikou, Konstantina | Gavra, Andromachi | Diamantidou, Alexandra | Kapsali, Nikolina | Kouroundi, Eleni | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer’s disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer’s disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). Objective: The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria …for SCD or MCI. Methods: Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Results: Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. Conclusions: The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field. Show more

Keywords: Alzheimer’s disease, Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-Greek), cutoff scores, discriminant validity, mild cognitive impairment, validation

DOI: 10.3233/ADR-230151

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 543-554, 2024

Authors: Brownell, Malcolm | Sehar, Ujala | Kshirsagar, Sudhir | Reddy, P. Hemachandra

Article Type: Article Commentary

Abstract: Our commentary aims to elucidate the importance of participant recruitment strategy in healthy brain aging study, particularly in rural West Texas, where more than 50% of the population are Hispanics and Latinos. The objective of our health aging study is to investigate the possible influence of biological, sociodemographic, and lifestyle factors on the occurrence of chronic diseases and dementia in the aging populations of West Texas. The success of this initiative is, in large part, reliant on high-quality, effective recruitment of participants. To that end, we propose an increase in our strategic recruitment efforts for both healthy, cognitively superior agers …as well as those with mild cognitive impairment and patients with Alzheimer’s disease in rural west Texas. We discussed, multi-advertising approaches, including ads in the local newspapers, local TV Channels and poster boards in senior centers. Show more

Keywords: Alzheimer’s disease, dementia, healthy aging, mild cognitive impairment, recruitment strategies, rural elderly

DOI: 10.3233/ADR-240009

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 555-559, 2024

Authors: Jiang, Jing | Wang, Zidong | Yu, Ruxia | Yang, Jiayi | Wang, Qiucheng | Wu, Guoqing | Tao, Yilin | Zhao, Xiaoyue | Wang, Yue | Li, Zhigang | Qin, Xiaoqian

Article Type: Research Article

Abstract: Background: Alzheimer’s disease may be effectively treated with acupoint-based acupuncture, which is acknowledged globally. However, more research is needed to understand the alterations in acupoints that occur throughout the illness and acupuncture treatment. Objective: This research investigated the differences in acupoint microcirculation between normal mice and AD animals in vivo . This research also examined how acupuncture affected AD animal models and acupoint microcirculation. Methods: 6-month-old SAMP8 mice were divided into two groups: the AD group and the acupuncture group. Additionally, SAMR1 mice of the same month were included as the normal group. The study involved …subjecting a group of mice to 28 consecutive days of acupuncture at the ST36 (Zusanli ) and CV12 (Zhongwan ) acupoints. Following this treatment, the Morris water maze test was conducted to assess the mice’s learning and memory abilities; the acoustic-resolution photoacoustic microscope (AR-PAM) imaging system was utilized to observe the microcirculation in CV12 acupoint region and head-specific region of each group of mice. Results: In comparison to the control group, the mice in the AD group exhibited a considerable decline in their learning and memory capabilities (p  < 0.01). In comparison to the control group, the vascular in the CV12 region and head-specific region in mice from the AD group exhibited a considerable reduction in length, distance, and diameter r (p  < 0.01). The implementation of acupuncture treatment had the potential to enhance the aforementioned condition to a certain degree. Conclusions: These findings offered tangible visual evidence that supports the ongoing investigation into the underlying mechanisms of acupuncture’s therapeutic effects. Show more

Keywords: Acupuncture, Alzheimer’s disease, microcirculation, photoacoustic microscope, senescence-accelerated mouse prone 8

DOI: 10.3233/ADR-230193

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 561-574, 2024

Authors: Zhu, Congcong | Tong, Tong | Farrell, John J. | Martin, Eden R. | Bush, William S. | Pericak-Vance, Margaret A. | Wang, Li-San | Schellenberg, Gerard D. | Haines, Jonathan L. | Lunetta, Kathryn L. | Farrer, Lindsay A. | Zhang, Xiaoling

Article Type: Research Article

Abstract: Background: Mitochondrial DNA (mtDNA) is a double-stranded circular DNA and has multiple copies in each cell. Excess heteroplasmy, the coexistence of distinct variants in copies of mtDNA within a cell, may lead to mitochondrial impairments. Accurate determination of heteroplasmy in whole-genome sequencing (WGS) data has posed a significant challenge because mitochondria carrying heteroplasmic variants cannot be distinguished during library preparation. Moreover, sequencing errors, contamination, and nuclear mtDNA segments can reduce the accuracy of heteroplasmic variant calling. Objective: To efficiently and accurately call mtDNA homoplasmic and heteroplasmic variants from the large-scale WGS data generated from the Alzheimer’s Disease Sequencing …Project (ADSP), and test their association with Alzheimer’s disease (AD). Methods: In this study, we present MitoH3—a comprehensive computational pipeline for calling mtDNA homoplasmic and heteroplasmic variants and inferring haplogroups in the ADSP WGS data. We first applied MitoH3 to 45 technical replicates from 6 subjects to define a threshold for detecting heteroplasmic variants. Then using the threshold of 5% ≤variant allele fraction≤95%, we further applied MitoH3 to call heteroplasmic variants from a total of 16,113 DNA samples with 6,742 samples from cognitively normal controls and 6,183 from AD cases. Results: This pipeline is available through the Singularity container engine. For 4,311 heteroplasmic variants identified from 16,113 samples, no significant variant count difference was observed between AD cases and controls. Conclusions: Our streamlined pipeline, MitoH3, enables computationally efficient and accurate analysis of a large number of samples. Show more

Keywords: Alzheimer’s disease, haplogroup, homoplasmic and heteroplasmic variant calling, mitochondrial DNA, whole genome sequencing

DOI: 10.3233/ADR-230120

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 575-587, 2024

Authors: Yu, Xianfeng | Deng, Shuqing | Liu, Junxin | Zhang, Mingkai | Zhang, Liang | Li, Ruixian | Zhang, Wei | Han, Ying

Article Type: Research Article

Abstract: Background: Sleep disturbances frequently affect Alzheimer’s disease (AD), with up to 65% patients reporting sleep-related issues that may manifest up to a decade before AD symptoms. Objective: To construct a nomogram that synthesizes sleep quality and cognitive performance for predicting cognitive impairment (CI) conversion outcomes. Methods: Using scores from three well-established sleep assessment tools, Pittsburg Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and Epworth Sleepiness Scale, we created the Sleep Composite Index (SCI), providing a comprehensive snapshot of an individual’s sleep status. Initially, a CI conversion prediction model was formed via COX regression, fine-tuned …by bidirectional elimination. Subsequently, an optimized prediction model through COX regression, depicted as a nomogram, offering predictions for CI development in 5, 8, and 12 years among cognitively unimpaired (CU) individuals. Results: After excluding CI patients at baseline, our study included 816 participants with complete baseline and follow-up data. The CU group had a mean age of 66.1±6.7 years, with 36.37% males, while the CI group had an average age of 70.3±9.0 years, with 39.20% males. The final model incorporated glial fibrillary acidic protein, Verbal Fluency Test and SCI, and an AUC of 0.8773 (0.792–0.963). Conclusions: In conclusion, the sleep-cognition nomogram we developed could successfully predict the risk of converting to CI in elderly participants and could potentially guide the design of interventions for rehabilitation and/or cognitive enhancement to improve the living quality for healthy older adults, detect at-risk individuals, and even slow down the progression of AD. Show more

Keywords: Alzheimer’s disease, biomarkers, prediction, sleep

DOI: 10.3233/ADR-240001

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 589-600, 2024

Authors: Batesole, Joshua | Tomkinson, Grant R. | Erickson, Kirk I. | Jurivich, Donald | Lang, Justin J. | McGrath, Brenda M. | Robinson-Lane, Sheria G. | Smith, Ashleigh E. | McGrath, Ryan

Article Type: Research Article

Abstract: Background: Weakness can be operationalized with several thresholds, which in turn, could impact associations with cognitive impairment when considering obesity status. Objective: We examined the associations of absolute, normalized, and collective weakness thresholds on future cognitive impairment by obesity status in older adults. Methods: We performed a secondary data analysis on the 2006–2018 waves of the Health and Retirement Study. A spring-type dynamometer collected handgrip strength (HGS). Males were categorized weak if their HGS was <35.5-kg (absolute), <0.45-kg/kg (body mass normalized), or <1.05-kg/kg/m2 (body mass index (BMI) normalized), while females were defined as weak if …their HGS was <20.0-kg, <0.337-kg/kg, or <0.79-kg/kg/m2 . The modified Telephone Interview of Cognitive Status examined cognitive function. Persons scoring ≤10 had a cognitive impairment. Obesity was categorized as BMI ≥30 kg/m2 . Results: We included 7,532 and 3,584 persons aged ≥65-years living without and with obesity, respectively. Those without obesity but beneath the absolute weakness threshold had 1.54 (95% confidence interval (CI): 1.24–1.91) greater odds for future cognitive impairment. Persons with obesity and beneath each threshold also had greater odds for future cognitive impairment: 1.89 (95% CI: 1.28–2.78) for absolute, 2.17 (95% CI: 1.02–4.62) for body mass normalized, and 1.75 (95% CI: 1.10–2.80) for BMI normalized. Older Americans without obesity but underneath all the weakness thresholds had 1.32 (95% CI: 1.00–1.74) greater odds for impairment in cognitive function, while persons with obesity had 2.76 (95% CI: 1.29–5.93) greater odds. Conclusions: There should be consideration for how body size and different weakness thresholds may influence future cognitive outcomes. Show more

Keywords: Aging, Alzheimer’s disease, body composition, body mass index, cognition, dementia, functional status, geriatrics, muscle strength, muscle strength dynamometer

DOI: 10.3233/ADR-230190

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 601-608, 2024

Authors: Hashiguchi, Kenichi | Kobayashi, Ryota | Morioka, Daichi | Kawakatsu, Shinobu | Sakamoto, Kazutaka | Matsuda, Hiroshi | Suzuki, Akihito

Article Type: Short Communication

Abstract: Identifying the coexistence of Lewy body (LB) pathology with Alzheimer’s disease (AD) in clinical practice is important in the era of anti-amyloid-β antibody therapy. However, few studies have predicted the presence of comorbid LB pathology with AD using indicative biomarkers of dementia with Lewy bodies or by collecting detailed clinical symptoms. We report the clinical progression of a 67-year-old patient diagnosed with AD who developed rapid eye movement sleep disorder-like symptoms and transient visual hallucinations 10 years after AD onset and was considered to have comorbid LB pathology based on imaging indicative biomarkers of dementia with Lewy bodies.

Keywords: Alzheimer’s disease, dementia, dopamine transporter, Lewy bodies, myocardial scintigraphy, rapid eye movement sleep behavior disorder, visual hallucinations

DOI: 10.3233/ADR-240019

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 609-614, 2024

Authors: Basurto-Islas, Gustavo | Tung, Yunn Chyn | Dai, Chun-ling | Iqbal, Khalid | Gong, Cheng-Xin

Article Type: Research Article

Abstract: Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer’s disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear. Objective: Our objective was to understand how DKA can promote neurodegeneration in AD. Methods: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation. Results: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of …tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin−protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA. Conclusions: These results shed some light on the mechanisms by which DKA may increase the risk for AD. Show more

Keywords: Dementia, diabetic ketoacidosis, protein kinases, protein phosphatases, tau

DOI: 10.3233/ADR-240040

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 615-626, 2024