Journal of Alzheimer's Disease - Volume 96, issue 2

Authors: Li, Yintong | Bian, Jinghua | Li, Yongna

Article Type: Research Article

Abstract: Background: Attention is an essential cognitive ability that is necessary in other cognitive processes. Only few studies have focused on decline in specific functions of attention in older adults with cognitive decline. No research explores the difference in the proactive and reactive mode of control between the healthy control (HC) and older adults with subjective cognitive decline (SCD). Objective: The current work investigated whether there was any decline in alerting, orienting, and executive control in SCD. Particularly, the present study further explored the impairment of the proactive and reactive control in SCD. Methods: We recruited 25 …HC and 26 SCD. All participants first finished a set of neuropsychological assessments. They then completed an Attention Network Test for measuring the alerting, orienting, and executive control, the List-wide and the Item-specific Proportion Congruency Effect task for measuring the proactive and reactive mode of control, respectively. Results: No difference was found in alerting, orienting, and executive control measured by the ANT between SCD and HC. The results also indicated no difference in the reactive control between SCD and HC. However, older adults with SCD performed worse in the proactive control as compared to HC. Conclusion: Older adults with SCD showed an impairment in the proactive control. The current findings help us better understand objective decline in cognitive domains other than memory and shed light on early assessment and prevention of AD. Show more

Keywords: Alzheimer’s disease, attention, attention network test, proactive control, reactive control, subjective cognitive decline

DOI: 10.3233/JAD-230037

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 551-561, 2023

Authors: Buchman, Aron S. | Leurgans, Sue E. | Kim, Namhee | Agrawal, Sonal | Oveisgharan, Shahram | Zammit, Andrea R. | VanderHorst, Veronique | Nag, Sukrit | Bennett, David A.

Article Type: Research Article

Abstract: Background: Assessments of Alzheimer’s disease pathology do not routinely include lower brainstem, olfactory bulb, and spinal cord. Objective: Test if amyloid-β (Aβ) and paired helical filament (PHF) tau-tangles outside the cerebrum are associated with the odds of dementia. Methods: Autopsies were obtained in decedents with cognitive testing (n  = 300). Aβ plaques and PHF tau-tangles were assessed in 24 sites: cerebrum (n  = 14), brainstem (n  = 5), olfactory bulb, and four spinal cord levels. Since spinal Aβ were absent in the first 165 cases, it was not assessed in the remaining cases. Results: Age at death …was 91 years old. About 90% had Aβ in cerebrum and of these, half had Aβ in the brainstem. Of the latter, 85% showed Aβ in the olfactory bulb. All but one participant had tau-tangles in the cerebrum and 86% had brainstem tau-tangles. Of the latter, 80% had tau-tangles in olfactory bulb and 36% tau-tangles in one or more spinal cord levels. About 90% of adults with tau-tangles also had Aβ in one or more regions. In a logistic model controlling for demographics, Aβ and tau-tangles within the cerebrum, the presence of Aβ in olfactory bulb [OR, 1.74(1.00, 3.05)]; tau-tangles in brainstem [OR, 4.00(1.1.57,10.21)]; and spinal cord [OR, 1.87 (1.21,3.11)] were independently associated with higher odds of dementia. Conclusion: Regional differences in Aβ and tau-tangle accumulation extend beyond cerebrum to spinal cord and their presence outside the cerebrum are associated with a higher odds of dementia. Further studies are needed to clarify the extent, burden, and consequences of AD pathology outside of cerebrum. Show more

Keywords: Alzheimer’s disease dementia, amyloid-β, PHF tau-tangles

DOI: 10.3233/JAD-230223

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 563-578, 2023

Authors: Heser, Kathrin | Kleineidam, Luca | Wagner, Michael | Luppa, Melanie | Löbner, Margrit | Wiese, Birgitt | Oey, Anke | König, Hans-Helmut | Brettschneider, Christian | van der Leeden, Carolin | van den Bussche, Hendrik | Fuchs, Angela | Pentzek, Michael | Weyerer, Siegfried | Werle, Jochen | Bickel, Horst | Scherer, Martin | Maier, Wolfgang | Ramirez, Alfredo | Riedel-Heller, Steffi G.

Article Type: Research Article

Abstract: Background: Subjective memory complaints and family history of dementia are possibly intertwined risk factors for the own subsequent dementia risk and Alzheimer’s disease. However, their interaction has rarely been studied. Objective: To study the association between subjective memory complaints and family history of dementia with regard to the own subsequent risk of dementia. Methods: Cross-sectional and longitudinal analyses over a follow-up period of up to 13 years were conducted in a population sample of participants without dementia at baseline (n = 3,256, mean age = 79.62 years), using group comparisons and Cox proportional hazards models. …Results: Cross-sectionally, participants with subjective memory complaints were significantly more likely to report family history of dementia. Longitudinally, family history of dementia (FH) was significantly associated with subsequent dementia in the subjective memory complaints (SMC) group, but not in those without SMC. A relative excess risk due to interaction analysis confirmed a significant FHxSMC-interaction. Conclusions: Family history of dementia was a predictor of incident dementia in those with SMC, which can serve as an additional, clinically relevant criterion to gauge the risk of dementia in older-aged subjects with SMC with and without objective cognitive impairment. Show more

Keywords: Aging, Alzheimer’s disease, cognitive complaints, dementia, family history of dementia, memory complaints, mild cognitive impairment, subjective cognitive decline, subjective cognitive impairment

DOI: 10.3233/JAD-230410

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 579-589, 2023

Authors: Roach, Jared C. | Rapozo, Molly K. | Hara, Junko | Glusman, Gwênlyn | Lovejoy, Jennifer | Shankle, William R. | Hood, Leroy | Atthara, Mouna | Baloni, Priyanka | Dill, Lauren | Edens, Lance E. | Fischer, Dan | Fortier, Dennis | Fridman, Deborah | Funk, Cory C. | Glusman, Gwênlyn | Hara, Junko | Hood, Leroy | Jade, Kathleen | Lovejoy, Jennifer C. | Magis, Andrew | Markewych, Daria R. | Price, Nathan | Rapozo, Molly K. | Roach, Jared C. | Shankle, William R.

Article Type: Research Article

Abstract: Background: Comprehensive treatment of Alzheimer’s disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. Personalized, multimodal therapies are needed to best prevent and treat Alzheimer’s disease (AD). Objective: The Coaching for Cognition in Alzheimer’s (COCOA) trial was a prospective randomized controlled trial to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage AD. Methods: Participants with early-stage AD were randomized into two arms. Arm 1 (N  = 24) received standard of care. Arm 2 (N  = 31) …additionally received telephonic personalized coaching for multiple lifestyle interventions. The primary outcome was a test of the hypothesis that the Memory Performance Index (MPI) change over time would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test was assessed for a secondary outcome. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints (dynamic dense data) across two years for each participant. Results: The intervention arm ameliorated 2.1 [1.0 ] MPI points (mean [SD], p  = 0.016) compared to the control over the two-year intervention. No important adverse events or side effects were observed. Conclusion: Multimodal lifestyle interventions are effective for ameliorating cognitive decline and have a larger effect size than pharmacological interventions. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic. Show more

Keywords: Alzheimer’s disease and related disorders, cognitive decline, cognitive impairment, cognitive training, diet, lifestyle, exercise, multimodal interventions, personalized 34 coaching, remote coaching

DOI: 10.3233/JAD-230403

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 591-607, 2023

Authors: Bian, Zhihong | Hu, Xinran | Liu, Xia | Yu, Haibo | Bian, Yuting | Sun, Hongming | Fukui, Yusuke | Morihara, Ryuta | Ishiura, Hiroyuki | Yamashita, Toru

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear. Objective: The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice. …Methods: In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter. Results: The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss. Conclusions: These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia. Show more

Keywords: Alzheimer’s disease, cerebral amyloid angiopathy, chronic cerebral hypoperfusion, rivaroxaban, white matter

DOI: 10.3233/JAD-230413

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 609-622, 2023

Authors: Xia, Siqi | Chen, Huaijun | Tang, Tianchi

Article Type: Research Article

Abstract: Background: No study has compared the risk of Alzheimer’s disease (AD) in patients with brain tumors, gliomas, or glioblastomas with the risk in patients with other tumors. Objective: To determine whether, compared with other tumors, brain tumors, gliomas, and glioblastomas increase the risk of AD. Methods: This study identified a case group of 24,441 patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with only one primary tumor at age > 20 years in 1975–2019 and died from AD at age > 65 years as case group. The control group comprised 122,205 subjects from the SEER …database who died from causes other than AD but otherwise had the same conditions as those in the case group. Results: There was a significantly lower prevalence of glioma (0.074% versus 0.14%, p  = 0.007) and glioblastoma (0.0082% versus 0.074%, p  = 0.001) in patients who died from AD than in those who died from other causes, while brain tumors were not significantly associated with AD death (p  = 0.227). When adjusted for factors including age at death, sex, race, tumor behavior, radiation therapy and tumor-directed surgery, glioblastoma was related to a significantly lower AD risk than other tumors (odds ratio: 0.19, 95% CI: 0.05–0.77). Additionally, patients who were older, female, American Indian/Alaska Native, had a benign tumor, radiation therapy and tumor-directed surgery had a significantly higher risk of dying from AD. Conclusion: Gliomas and glioblastomas were associated with a significantly lower risk of death from AD than other tumors. Show more

Keywords: Alzheimer’s disease, brain tumor, cancer, glioblastoma, glioma, risk, tumor

DOI: 10.3233/JAD-230554

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 623-631, 2023

Authors: Kim, Minjae | Yi, Dahyun | Byun, Min Soo | Ahn, Hyejin | Jung, Joon Hyung | Kong, Nayeong | Chang, Yoonyoung | Choi, Hyeji | Choi, Jungmin | Kim, Kyungtae | Jung, Gijung | Lee, Dong Young

Article Type: Research Article

Abstract: Background: As tracking subtle cognitive declines in the preclinical stage of Alzheimer’s disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized. Objective: We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults. Methods: A total 225 cognitively normal elderly individuals from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, were included. Tests of episodic memory, orientation, and executive function were carefully selected through review of previously established composites. Three …candidate composites including Consortium to Establish a Registry for Alzheimer’s Disease Word list recall (WLR), Logical memory (LM) II, and Mini-Mental status examination (MMSE) in common, and Letter fluency test (LF), category fluency test, or Stroop color and word test, were selected. Results: Student t -tests demonstrated that only the composite composed of WLR, LM II, MMSE, and LF (Composite 1) showed a significant difference in score decline over two-year follow-up period between Aβ positive and negative group (p  = 0.03). Linear mixed model analyses also showed that the Aβ x time interaction effect was significant only for Composite 1 (p  = 0.025). Based on the results, Composite 1 was chosen as the final cognitive composite for preclinical Alzheimer’s disease (CPAD). Conclusions: CPAD can be used to assess subtle cognitive decline of preclinical AD in clinical research settings, especially in Korean older adults. It also may be used for monitoring progression or treatment benefits in clinical practices. Show more

Keywords: Alzheimer’s disease, cognitive composite, cognitively normal, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-230263

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 633-641, 2023

Authors: Li, Anqi | Du, Jing | Cai, Yue | Chen, Xuhui | Sun, Kun | Guo, Tengfei

Article Type: Research Article

Abstract: Background: Body mass index (BMI) changes may be related to Alzheimer’s disease (AD) alterations, but it is unclear how the apolipoprotein E ɛ4 (APOE ɛ4) allele affects their association. Objective: To explore the association of BMI changes with AD pathologies in APOE ɛ4 carriers and non-carriers. Methods: In 862 non-demented ADNI participants with≥2 BMI measurements, we investigated the relationships between BMI slopes and longitudinal changes in amyloid-β (Aβ) accumulation, neurodegeneration and cognition, and follow-up tau deposition in different Aβ and APOE ɛ4 statuses. Results: In Aβ+ APOE ɛ4 non-carriers, faster …BMI declines were associated with faster rates of Aβ accumulation (standardized β (βstd ) = –0.29, p  = 0.001), AD meta regions of interest (metaROI) hypometabolism (βstd  = 0.23, p  = 0.026), memory declines (βstd  = 0.17, p  = 0.029), executive function declines (βstd  = 0.19, p  = 0.011), and marginally faster Temporal-metaROI cortical thinning (βstd  = 0.15, p  = 0.067) and higher follow-up Temporal-metaROI tau deposition (βstd  = –0.17, p  = 0.059). Among Aβ- individuals, faster BMI decreases were related to faster Aβ accumulation (βstd  = –0.25, p  = 0.023) in APOE ɛ4 carriers, whereas predicted faster declines in memory and executive function in both APOE ɛ4 carriers (βstd  = 0.25, p  = 0.008; βstd  = 0.32, p  = 0.001) and APOE ɛ4 non-carriers (βstd  = 0.11, p  = 0.030; βstd  = 0.12, p  = 0.026). Conclusions: This study highlights the significance of tracking BMI data in older adults by providing novel insights into how body weight fluctuations and APOE ɛ4 interact with AD pathology and cognitive decline. Show more

Keywords: Alzheimer’s disease, apolipoprotein E ɛ4, body mass index, cognitive decline, neurodegeneration

DOI: 10.3233/JAD-230446

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 643-655, 2023

Authors: Han, Xiaolei | Song, Lin | Li, Yuanjing | Dong, Yi | Liu, Rui | Han, Qi | Wang, Xiaojie | Mao, Ming | Cong, Lin | Tang, Shi | Hou, Tingting | Zhang, Qinghua | Liu, Cuicui | Han, Xiaodong | Shi, Lin | Nyberg, Lars | Launer, Lenore J. | Wang, Yongxiang | Du, Yifeng | Qiu, Chengxuan

Article Type: Research Article

Abstract: Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms. Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018–2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n  = 1,009). Data …were analyzed using the general linear, isotemporal substitution, and mediation models. Results: In the total sample (n  = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z- scores of global cognition, verbal fluency, and memory (ptrend  < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend  < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z- scores (p  < 0.05). In the MRI subsample (n  = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z- scores. Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association. Show more

Keywords: Accelerometer, Alzheimer’s disease, brain aging, cognition, magnetic resonance imaging, population-based study, sedentary behavior patterns

DOI: 10.3233/JAD-230575

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 657-668, 2023

Authors: Jiang, Jiwei | Hong, Yin | Li, Wenyi | Wang, Anxin | Jiang, Shirui | Jiang, Tianlin | Wang, Yanli | Wang, Linlin | Yang, Shiyi | Ren, Qiwei | Zou, Xinying | Xu, Jun

Article Type: Research Article

Abstract: Background: Apolipoprotein E (APOE ) is the most recognized risk gene for cognitive decline and clinical progression of late-onset Alzheimer’s disease (AD); nonetheless, its association with neuropsychiatric symptoms (NPSs) remains inconclusive. Objective: To investigate the association of APOE ɛ4 with NPSs and explore nutritional status and cognition as joint mediators of this association. Methods: Between June 2021 and October 2022, patients with amnestic mild cognitive impairment (aMCI) or AD were recruited from the Chinese Imaging, Biomarkers, and Lifestyle Study. NPSs were assessed using the Neuropsychiatric Inventory, while global cognition and nutritional status were evaluated using …the Mini-Mental State Examination (MMSE) and Mini-Nutritional Assessment (MNA), respectively. Simple mediation and multiple chain mediation models were developed to examine the mediating effects of the MNA and MMSE scores on the relationship between APOE ɛ4 and specific neuropsychiatric symptom. Results: Among 310 patients, 229 (73.87%) had NPSs, and 110 (35.48%) carried APOE ɛ4. Patients with APOE ɛ4 were more likely to have hallucinations (p  = 0.014), apathy (p  = 0.008), and aberrant motor activity (p  = 0.018). MNA and MMSE scores mediated the association between APOE ɛ4 and hallucinations (17.97% and 37.13%, respectively), APOE ɛ4 and apathy (30.73% and 57.72%, respectively), and APOE ɛ4 and aberrant motor activity (17.82% and 34.24%), respectively. Chain-mediating effects of MNA and MMSE scores on the association of APOE ɛ4 with hallucinations, apathy, and aberrant motor activity after adjusting for confounding factors were 6.84%, 11.54%, and 6.19%, respectively. Conclusion: Nutritional status and cognition jointly mediate the association between APOE ɛ4 and neuropsychiatric symptoms in patients with aMCI or AD. Show more

Keywords: Alzheimer’s disease, cognition, mediation analysis, mild cognitive impairment, neuropsychiatric symptoms, nutrition

DOI: 10.3233/JAD-230577

Citation: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 669-681, 2023