Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Lerner, Alan J.

Article Type: Research Article

Abstract: After years of anticipation, non-invasive tests for detecting cerebral amyloidosis and Alzheimer’s disease (AD) are entering clinical care. The PrecivityADtrademark test from C2N is a plasma-based test yielding an Amyloid Probability score with high sensitivity and specificity for brain amyloid accumulation, but some samples may have inconclusive results. The AGREEDementia consortium raised concerns that the field needs study of how best to use and communicate results of PrecivityADtrademark. Continued attention and mindfulness should be applied to the whole class of dementia biomarker tests and directed in light of FDA biomarker context of use framework. Unintended uses of biomarkers tests may …have unintended consequences, such as mislabeling patients. AD biomarker tests may efficiently stratify AD risk but will inevitably be included in electronic medical records and be subject to interpretation by medical personnel lacking proper knowledge or context to interpret results appropriately. Another way forward is mindful discussion and consensus among all stakeholders about the uses and limits of each specific test. Show more

Keywords: Alzheimer’s disease, amyloid, biomarkers, dementia, mindfulness, plasma, prediction

DOI: 10.3233/JAD-215592

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2022

Authors: Walter, Sarah | Kim, Anne B. | Flores, Melissa | Ziolkowski, Jaimie | Shaffer, Elizabeth | Aggarwal, Neelum T.

Article Type: Research Article

Abstract: Background: Study participants, patients, and care partners are key stakeholders in research and have asked for greater inclusion in the dissemination of scientific learning. However, the participation of general audiences in scientific conferences dedicated to Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) is not widely supported or studied. Objective: Our objectives were to evaluate the interest, level of engagement, and impact of including general audiences in a virtual dementia conference. Methods: A diverse group of lay participants, identified via community-based health advocacy groups and research centers, were invited to attend the 2021 Alzheimer’s Association International …Conference (AAIC), with optional small-group discussions. Participants received complimentary access to all scientific sessions and were supported via navigation tips, recommended sessions, and a glossary of frequently used terms and acronyms. Results: Lay participants demonstrated a high level of engagement, even among those that were research-naïve, attending virtual sessions for an average of 11.7 hours across the five days and recommending a variety of sessions to each other on topics extending from prevention of dementia to new therapies and care. Most participants said they would attend the conference again and rated the quality of interaction as high, while requesting more opportunities to engage directly with researchers. Conclusion: General audiences, in particular research participants, are advocating for greater participation in scientific conferences. This program can serve as a model to accomplish inclusion; thereby acknowledging their invaluable contribution to science. Show more

Keywords: Dementia, patient activation, patient inclusion, patients and conferences, research participants

DOI: 10.3233/JAD-215681

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Jester, Hannah | Gosrani, Saahj | Ding, Huiping | Zhou, Xueyan | Ko, Mei-Chuan | Ma, Tao

Article Type: Research Article

Abstract: Background: Sporadic or late onset Alzheimer’s disease (LOAD) is a multifactorial neurodegenerative disease with aging the most known risk factor. Non-human primates (NHPs) may serve as an excellent model to study LOAD because of their close similarity to humans in many aspects including neuroanatomy and neurodevelopment. Recent studies reveal AD-like pathology in old NHPs. Objective: In this pilot study, we took advantage of brain samples from 6 Cynomolgus macaques that were divided into two groups: middle aged (average age 14.81 years) and older (average age 19.33 years). We investigated whether AD-like brain pathologies are present in the NHPs. …Methods: We used immunohistochemical method to examine brain Aβ pathology and neuron density. We applied biochemical assays to measure tau phosphorylation and multiple signaling pathways indicated in AD. We performed electron microscopy experiments to study alterations of postsynaptic density and mitochondrial morphology in the brain of NHPs. Results: We found multiple AD-like pathological alteration in the prefrontal cortex (but not in the hippocampus) of the older NHPs including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology, and postsynaptic densities formation. Conclusion: These findings may provide insights into the factors contributing to the development of LOAD, particularly during the early stage transitioning from middle to old age. Future endeavors are warranted to elucidate mechanisms underlying the regional (and perhaps cellular) vulnerability with aging and the functional correlation of such pathological changes in NHPs. Show more

Keywords: Aging, Alzheimer’s disease, AMPK, mitochondria, non-human primate, synapses

DOI: 10.3233/JAD-215303

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Weissberger, Gali H. | Samek, Anya | Mosqueda, Laura | Nguyen, Annie L. | Lim, Aaron C. | Fenton, Laura | Han, S. Duke

Article Type: Research Article

Abstract: Background: Older age is associated with an increase in altruistic behaviors such as charitable giving. However, few studies have investigated the cognitive correlates of financial altruism in older adults. Objective: This study investigated the cognitive correlates of financial altruism measured using an altruistic choice paradigm in a community-based sample of older adults. Methods: In the present study, a sample of older adults (N  = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD  = 2.51; 58.2% female; 71.6% Non-Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating …money between themselves and an anonymous person. Results: In multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s disease (including word list learning and recall, delayed story recall, and animal fluency). Conclusion: Findings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s disease. Findings also point to a potential link between financial exploitation risk and Alzheimer’s disease in older age. Show more

Keywords: Altruism, Alzheimer’s disease, cognition, economic factors, episodic memory

DOI: 10.3233/JAD-220187

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Kobayashi, Masatomo | Yamada, Yasunori | Shinkawa, Kaoru | Nemoto, Miyuki | Nemoto, Kiyotaka | Arai, Tetsuaki

Article Type: Research Article

Abstract: Background: Automatic analysis of the drawing process using a digital tablet and pen has been applied to successfully detect Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, most studies focused on analyzing individual drawing tasks separately, and the question of how a combination of drawing tasks could improve the detection performance thus remains unexplored. Objective: We aimed to investigate whether analysis of the drawing process in multiple drawing tasks could capture different, complementary aspects of cognitive impairments, with a view toward combining multiple tasks to effectively improve the detection capability. Methods: We collected drawing data …from 144 community-dwelling older adults (27 AD, 65 MCI, and 52 cognitively normal, or CN) who performed five drawing tasks. We then extracted motion- and pause-related drawing features for each task and investigated the statistical associations of the features with the participants’ diagnostic statuses and cognitive measures. Results: The drawing features showed gradual changes from CN to MCI and then to AD, and the changes in the features for each task were statistically associated with cognitive impairments in different domains. For classification into the three diagnostic categories, a machine learning model using the features from all five tasks achieved a classification accuracy of 75.2%, an improvement by 7.8% over that of the best single-task model. Conclusion: Our results demonstrate that a common set of drawing features from multiple drawing tasks can capture different, complementary aspects of cognitive impairments, which may lead to a scalable way to improve the automated detection of AD and MCI. Show more

Keywords: Alzheimer’s disease, digital technology, drawing, handwriting, machine learning, mild cognitive impairment, neuropsychological tests

DOI: 10.3233/JAD-215714

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2022

Authors: Mielke, Michelle M. | Ransom, Jeanine E. | Mandrekar, Jay | Turcano, Pierpaolo | Savica, Rodolfo | Brown, Allen W.

Article Type: Research Article

Abstract: Background: Epidemiological studies examining associations between traumatic brain injury (TBI) and Alzheimer’s disease and related dementias (ADRD) have yielded conflicting results, which may be due methodological differences. Objective: To examine the relationship between the presence and severity of TBI and risk of ADRD using a population-based cohort with medical record abstraction for confirmation of TBI and ADRD. Methods: All TBI events among Olmsted County, Minnesota residents aged >  40 years from 1985–1999 were confirmed by manual review and classified by severity. Each TBI case was randomly matched to two age-, sex-, and non-head injury population-based referents without …TBI. For TBI events with non-head trauma, the Trauma Mortality Prediction Model was applied to assign an overall measure of non-head injury severity and corresponding referents were matched on this variable. Medical records were manually abstracted to confirm ADRD diagnosis. Cox proportional hazards models examined the relationship between TBI and severity with risk of ADRD. Results: A total of 1,418 residents had a confirmed TBI (865 Possible, 450 Probable, and 103 Definite) and were matched to 2,836 referents. When combining all TBI severities, the risk of any ADRD was significantly higher for those with a confirmed TBI compared to referents (HR = 1.32, 95% CI: 1.11, 1.58). Stratifying by TBI severity, Probable (HR = 1.42, 95% CI: 1.05, 1.92) and Possible (HR = 1.29, 95% CI: 1.02–1.62) TBI was associated with an increased risk of ADRD, but not Definite TBI (HR = 1.22, 95% CI: 0.68, 2.18). Conclusion: Our analyses support including TBI as a potential risk factor for developing ADRD. Show more

Keywords: Alzheimer’s disease, dementia, epidemiology, Parkinson’s disease, population, traumatic brain injury

DOI: 10.3233/JAD-220159

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Leonhardi, Jakob | Barthel, Henryk | Speerforck, Sven | Dietzel, Jens | Schroeter, Matthias L. | Saur, Dorothee | Tiepolt, Solveig | Rullmann, Michael | Patt, Marianne | Claßen, Joseph | Schomerus, Georg | Sabri, Osama

Article Type: Research Article

Abstract: Background: Alzheimer’s disease and depression can start with combined cognitive and depressive symptoms [1, 2 ]. Accurate differential diagnosis is desired to initiate specific treatment. Objective: We investigated whether amyloid-β PET imaging can discriminate both entities. Methods: This retrospective observational study included 39 patients (20 female, age = 70±11years) with both cognitive and depressive symptoms who underwent amyloid-β PET imaging and in whom clinical follow-up data was available. Amyloid-β PET was carried out applying [18 F]Florbetaben or [11 C]PiB. The PET images were analyzed by standardized visual and relative-quantitative evaluation. Based on clinical follow-up (median of 2.4 years …[range 0.3 to 7.0 years, IQR = 3.7 years] after amyloid PET imaging which was not considered in obtaining a definite diagnosis), discrimination ability between AD-related depression and pseudo-dementia in depression/depression with other comorbidities was determined. Results: Visually, all 10 patients with pseudo-dementia in depression and all 15 patients with other depression were rated as amyloid-β-negative; 2 of 14 patients with AD-related depression were rated amyloid-β–negative. ROC curve analysis of the unified composite standardized uptake value ratios (cSUVRs) was able to discriminate pseudo-dementia in depression from AD-related depression with high accuracy (AUC = 0.92). Optimal [18 F]Florbetaben discrimination cSUVR threshold was 1.34. In congruence with the visual PET analysis, the resulting sensitivity of the relative-quantitative analysis was 86% with a specificity of 100% . Conclusion: Amyloid-β PET can differentiate AD-related depression and pseudo-dementia in depression. Prospective clinical studies are warranted to confirm this result and to potentially broaden the spectrum of clinical applications for amyloid-β PET imaging. Show more

Keywords: Alzheimer’s disease, amyloid-β, amyloid PET imaging, depression, [18F]florbetaben, mild cognitive impairment, pittsburgh compound B, pseudo-dementia

DOI: 10.3233/JAD-215619

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2022

Authors: Bukhbinder, Avram S. | Ling, Yaobin | Hasan, Omar | Jiang, Xiaoqian | Kim, Yejin | Phelps, Kamal N. | Schmandt, Rosemarie E. | Amran, Albert | Coburn, Ryan | Ramesh, Srivathsan | Xiao, Qian | Schulz, Paul E.

Article Type: Research Article

Abstract: Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer’s disease (AD) risk in a general cohort of older US adults has not been characterized. Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year …look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. Results: From the unmatched sample of eligible patients (n  = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n  = 47,889) of the flu-vaccinated patients and 8.5% (n  = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4. Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older. Show more

Keywords: Alzheimer’s disease, cohort studies, incidence, influenza vaccines, pharmacoepidemiology, retrospective studies, vaccination

DOI: 10.3233/JAD-220361

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Teichmann, Birgit | Gkioka, Mara | Kruse, Andreas | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: Dementia is rapidly increasing worldwide due to demographic aging. More than two-thirds of patients are cared by family members. The quality of care depends on the caregivers’ attitude toward dementia influencing patient care decisions. Objective: The aim of this study is to examine the factors that influence the caregivers’ attitude and whether there is an association between participation in a psycho-educational program and attitude. Methods: We performed a cross-sectional study using a structured closed-ended questionnaire to retrieve socio-demographic information from caregivers and the persons with dementia (N = 86). The study included validated scales such as the …Dementia Attitude Scale, the Dementia Knowledge Assessment Tool 2, the Positive Aspects of Caregiving, the Zarit Burden Interview, the Confidence in Dementia Scale, and Spielberger’s State-Trait Anxiety Inventory, as well as a neuropsychological battery to assess the condition of people with dementia. Results: Our final model explains 55.6% of the total variance and shows a significant correlation of five factors with attitude toward dementia: confidence, behavioral and psychological symptoms of dementia, anxiety as a trait, positive aspects of caregiving, and dementia knowledge. The caregivers who participated in a psycho-educational program showed a significantly more positive attitude toward dementia, better dementia knowledge, higher confidence in dementia care, and lower anxiety as a state. Conclusion: The strong correlation of attitude and knowledge, as well as confidence in dementia care, supports the tripartite model of attitude, which hypothesizes the interrelation of affect, cognition, and behavior. Show more

Keywords: Anxiety, attitude, caregiver burden, dementia, family caregiver, knowledge

DOI: 10.3233/JAD-215731

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Horvath, Alexandra | Quinlan, Patrick | Eckerström, Carl | Åberg, N. David | Wallin, Anders | Svensson, Johan

Article Type: Research Article

Abstract: Background: Serum insulin-like growth factor-I (IGF-I) has shown some association with hippocampal volume in healthy subjects, but this relation has not been investigated in stable mild cognitive impairment (sMCI) or Alzheimer’s disease (AD). Objective: At a single memory clinic, we investigated whether serum IGF-I was associated with baseline magnetic resonance imaging (MRI)-estimated brain volumes and longitudinal alterations, defined as annualized changes, up to 6 years of follow-up. Methods: A prospective study of patients with sMCI (n  = 110) and AD (n  = 60). Brain regions included the hippocampus and amygdala as well as the temporal, parietal, frontal, and …occipital lobes, respectively. Results: Serum IGF-I was statistically similar in sMCI and AD patients (112 versus 123 ng/mL, p  = 0.31). In sMCI, serum IGF-I correlated positively with all baseline MRI variables except for the occipital lobe, and there was also a positive correlation between serum IGF-I and the annualized change in hippocampal volume (r  _ s = 0.32, p  = 0.02). Furthermore, sMCI patients having serum IGF-I above the median had lower annual loss of hippocampal volume than those with IGF-I below the median (p  = 0.02). In contrast, in AD patients, IGF-I did not associate with baseline levels or annualized changes in brain volumes. Conclusion: In sMCI patients, our results suggest that IGF-I exerted neuroprotective effects on the brain, thereby maintaining hippocampal volume. In AD, serum IGF-I did not associate with brain volumes, indicating that IGF-I could not induce neuroprotection in this disease. This supports the notion of IGF-I resistance in AD. Show more

Keywords: Alzheimer’s disease, brain region volume, hippocampus, insulin-like growth factor, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-220292

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022