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

Authors: Hu, Emily A. | Wu, Aozhou | Dearborn, Jennifer L. | Gottesman, Rebecca F. | Richey Sharrett, A. | Steffen, Lyn M. | Coresh, Josef | Rebholz, Casey M.

Article Type: Research Article

Abstract: Background: Previous studies have suggested that adherence to healthy dietary patterns during late life may be associated with improved cognition. However, few studies have examined the association between healthy dietary patterns during midlife and incident dementia. Objective: Our study aimed to determine the association between adherence to healthy dietary patterns at midlife and incident dementia. Methods: We included 13,630 adults from the Atherosclerosis Risk in Communities (ARIC) Study in our prospective analysis. We used food frequency questionnaire responses to calculate four dietary scores: Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean (aMed) diet, …and Dietary Approaches to Stop Hypertension (DASH). Participants were followed until the end of 2017 for incident dementia. Cox regression models adjusted for covariates were used to estimate risk of incident dementia by quintile of dietary scores. Results: Over a median of 27 years, there were 2,352 cases of incident dementia documented. Compared with participants in quintile 1 of HEI-2015, participants in quintile 5 (healthiest) had a 14% lower risk of incident dementia (hazard ratio, HR: 0.86, 95% confidence interval, CI: 0.74–0.99). There were no significant associations of incident dementia with the AHEI-2010, aMed, or DASH scores. There were no significant interactions by sex, age, race, education, physical activity, hypertension, or obesity. Conclusion: Adherence to the HEI-2015, but not the other dietary scores, during midlife was associated with lower risk of incident dementia. Further research is needed to elucidate whether timing of a healthy diet may influence dementia risk. Show more

Keywords: AHEI-2010, cognition, DASH, dementia, dietary pattern, HEI-2015, Mediterranean diet

DOI: 10.3233/JAD-200392

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Hüttenrauch, Melanie | Lopez-Noguerola, José Sócrates | Castro-Obregón, Susana

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disorder that represents a major and increasing global health challenge. In most cases, the first clinical symptoms of AD are preceded by neuropathological changes in the brain that develop years to decades before their onset. Therefore, research in the last years has focused on this preclinical stage of AD trying to discover intervention strategies that might, if implemented effectively, delay or prevent disease progression. Among those strategies, mind-body therapies such as yoga and meditation have gained increasing interest as complementary alternative interventions. Several studies have reported a positive impact of yoga and …meditation on brain health in both healthy older adults and dementia patients. However, the underlying neurobiological mechanisms contributing to these effects are currently not known in detail. More specifically, it is not known whether yogic interventions, directly or indirectly, can modulate risk factors or pathological mechanisms involved in the development of dementia. In this article, we first review the literature on the effects of yogic practices on outcomes such as cognitive functioning and neuropsychiatric symptoms in patients with mild cognitive impairment and dementia. Then, we analyze how yogic interventions affect different risk factors as well as aspects of AD pathophysiology based on observations of studies in healthy individuals or subjects with other conditions than dementia. Finally, we integrate this evidence and propose possible mechanisms that might explain the positive effects of yogic interventions in cognitively impaired individuals. Show more

Keywords: Alzheimer’s disease, dementia, mind-body therapy, mild cognitive impairment, meditation, yoga

DOI: 10.3233/JAD-200743

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-26, 2020

Authors: Huang, Zhenting | Yan, Qian | Wang, Yangyang | Zou, Qian | Li, Jing | Liu, Zhou | Cai, Zhiyou

Article Type: Review Article

Abstract: Mitochondrial dysfunction has been widely reported in several neurodegenerative disorders, including in the brains of patients with Alzheimer’s disease (AD), Parkinson’s disease, and Huntington disease. An increasing number of studies have implicated altered glucose and energy metabolism in patients with AD. There is compelling evidence of abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase and α -ketoglutarate dehydrogenase complexes, which play a great significance role in the pathogenesis of AD. Changes in some of the enzyme activities of the mitochondria found in AD have been linked with the pathology of amyloid-β (Aβ). …This review highlights the role of mitochondrial function in the production and clearance of Aβ and how the pathology of Aβ leads to a decrease in energy metabolism by affecting mitochondrial function. Show more

Keywords: Alzheimer’s disease, amyloid-β , dysfunction, mitochondria, pathology

DOI: 10.3233/JAD-200519

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2020

Authors: Khedr, Eman M. | Gomaa, Asmaa M.S. | Ahmed, Omyma G. | Sayed, Hanaa M.M. | Gamea, Ayman

Article Type: Research Article

Abstract: Background: There are currently few biomarkers to assist in early diagnosis of dementias. Objective: To distinguish between different dementias: Alzheimer’s disease (AD), vascular dementia (VaD), and Parkinson’s disease dementia (PDD) using simple neurophysiologic (P300) and laboratory markers (transforming growth factor β 1 “TGF-β 1”). Methods: The study included 15 patients for each type of dementia and 25 age- and sex-matched control subjects. Dementia patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition-revised (DSM-IV-R). Modified Mini-Mental State Examination (3MS), Memory Assessment Scale (MAS), P300, and TGF-β 1 were examined for each …participant. Results: There were no significant differences between groups as regard to age, sex, and education, social, and economic levels. Significant differences between groups were observed in registration and naming variables of the 3MS. Compared with the control group, P300 latency was prolonged in all groups, although to a greater extent in AD and PDD than in VaD. A serum level of TGF-β 1 was significantly elevated in all groups but was significantly higher in AD and VaD than in PDD. 3MS tended to correlate with P300 more than TGF-β 1, and to be stronger in AD than the other groups. Conclusion: Measurements of P300 latency and serum levels of TGF-β 1 can help distinguish AD, PDD, and VaD. P300 was more prolonged in AD and PDD than VaD whereas TGF-β 1 was significantly higher in AD and VaD than PDD. Thus P300 and TGF-β 1 may be useful biomarkers for detection and evaluation of the extent of cognitive dysfunction. Show more

Keywords: Alzheimer’s disease, event related potential P300, Modified Mini-Mental State Examination, Parkinson’s disease dementia, transforming growth factor β1, vascular dementia

DOI: 10.3233/JAD-200885

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Tsolaki, Magda | Lazarou, Eftychia | Kozori, Mahi | Petridou, Niki | Tabakis, Irene | Lazarou, Ioulietta | Karakota, Maria | Saoulidis, Iordanis | Melliou, Eleni | Magiatis, Prokopios

Article Type: Research Article

Abstract: Background: Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function. Objective: To investigate for the first time the effect of Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) in people with mild cognitive impairment (MCI). Methods: We conducted a randomized prospective study so as to examine the HP-EH-EVOO and MP-EVOO versus MeDi in MCI. Genetic predisposition (APOE ɛ 4) to Alzheimer’s disease (AD) was tested and an extensive neuropsychological battery was administered at baseline and after 12 months. Each …participant was randomized and assigned one of three groups: 1) Group 1 received the HP-EH-EVOO (50 mL/day); 2) Group 2 received the MP-EVOO (50 mL/day), and 3) Group 3 received only the MeDi instructions. Results: Better follow-up performance was found in Group 1 compared to Group 2 and Group 3 in the almost all cognitive domains. Moreover, Group 2 showed also significant improvement compared to Group 3 in ADAS-cog (p  = 0.001) and MMSE (p  = 0.05), whereas Group 3 exhibited worse or similar to baseline performance in almost all domains. In particular, Group 1 and Group 2 had better outcomes with regards to ADAS-cog (p  = 0.003), Digit Span (p  = 0.006), and Letter fluency (p  = 0.003). Moreover, there was a significant difference (p  = 0.001) in the presence of APOE ɛ 4 between the Groups 1 and 2 versus Group 3. Conclusion: Long-term intervention with HP-EH-EVOO or MP-EVOO was associated with significant improvement in cognitive function compared to MeDi, independent of the presence of APOE ɛ 4. Show more

Keywords: Alzheimer’s disease, APOE, extra virgin olive oil, Mediterranean Diet, mild cognitive impairment, natural compounds, non-pharmaceutical interventions

DOI: 10.3233/JAD-200405

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2020

Authors: Snowden, Taylor M. | Hinde, Anthony K. | Reid, Hannah M.O. | Christie, Brian R.

Article Type: Research Article

Abstract: Background: Mild traumatic brain injury (mTBI) is a putative risk factor for dementia; however, despite having apparent face validity, the evidence supporting this hypothesis remains inconclusive. Understanding the role of mTBI as a risk factor is becoming increasingly important given the high prevalence of mTBI, and the increasing societal burden of dementia. Objective: Our objective was to use the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) format to determine if an association exists between mTBI and dementia and related factors, and to quantify the degree of risk. Methods: In this format, two authors conducted …independent database searches of PubMed, PsycInfo, and CINAHL using three search blocks to find relevant papers published between 2000 and 2020. Relevant studies were selected using pre-defined inclusion/exclusion criteria, and bias scoring was performed independently by the two authors before a subset of studies was selected for meta-analysis. Twenty-one studies met the inclusion criteria for this systematic review. Results: The meta-analysis yielded a pooled odds ratio of 1.96 (95% CI 1.698–2.263), meaning individuals were 1.96 times more likely to be diagnosed with dementia if they had a prior mTBI. Most studies examining neuropsychiatric and neuroimaging correlates of dementia found subtle, persistent changes after mTBI. Conclusion: These results indicate that mTBI is a risk factor for the development of dementia and causes subtle changes in performance on neuropsychiatric testing and brain structure in some patients. Show more

Keywords: Alzheimer’s disease, dementia, mild traumatic brain injury

DOI: 10.3233/JAD-200662

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-19, 2020

Authors: Stonnington, Cynthia M. | Velgos, Stefanie N. | Chen, Yinghua | Syed, Sameena | Huentelman, Matt | Thiyyagura, Pradeep | Lee, Wendy | Richholt, Ryan | Caselli, Richard J. | Locke, Dona E.C. | Lu, Bai | Reiman, Eric M. | Su, Yi | Chen, Kewei

Article Type: Research Article

Abstract: Background: Whether brain-derived neurotrophic factor (BDNF ) Met carriage impacts the risk or progression of Alzheimer’s disease (AD) is unknown. Objective: To evaluate the interaction of BDNF Met and APOE 4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. Methods: 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B …(PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. Results: Among APOE 4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE 4 non-carriers. Conclusion: Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE 4 on amyloid-β plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity—findings that would need to be confirmed in larger studies. Show more

Keywords: Amyloid, APOE4, BDNF, cognition, fluorodeoxyglucose F18, positron emission tomography

DOI: 10.3233/JAD-200132

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: El Haj, Mohamad | Allain, Philippe | Annweiler, Cédric | Boutoleau-Bretonnière, Claire | Chapelet, Guillaume | Gallouj, Karim | Kapogiannis, Dimitrios | Roche, Jean | Boudoukha, Abdel Halim

Article Type: Research Article

Abstract: Background/Objective: The COVID-19 crisis has been increasing the burden of healthcare workers in acute care geriatric facilities. These workers have been dealing with drastic changes in the care they provide to their residents including cancelation of group activities and communal dining and even restrictions of activities outside rooms. Healthcare workers have also been devoting more time and energy to perform COVID-related medical duties. Geriatric facilities have been facing shortages in equipment and supplies, as well as staffing shortages. Finally, healthcare workers have been facing challenges regarding their personal safety and that of their families. Consequently, we hypothesized the presence of …high levels of burnout among healthcare workers during the COVID-19 crisis. Methods: To evaluate burnout in healthcare workers in French acute care geriatric facilities, we used an online survey based on the Oldenburg Burnout Inventory. Eighty-four healthcare workers answered the survey, during April of 2020. Results: Analysis demonstrated that they were experiencing medium levels of burnout, exhaustion, and disengagement. Conclusion: This level of burnout reflected their fatigue, loss of energy, and/or feelings of being overextended and exhausted. Considering the expected cumulative impact of various stressors, the medium level of burnout observed has come as a surprise to us and might actually be considered as relatively good news. Nevertheless, no level of burnout is negligible and has wide ranging negative consequences. Show more

Keywords: Burnout, caregivers, COVID-19, geriatric facilities

DOI: 10.3233/JAD-201029

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Ravona-Springer, Ramit | Sharvit-Ginon, Inbal | Ganmore, Ithamar | Greenbaum, Lior | Bendlin, Barbara B. | Sternberg, Shelley A. | Livny, Abigail | Domachevsky, Liran | Sandler, Israel | Ben Haim, Simona | Golan, Sapir | Ben-Ami, Liat | Lesman- Segev, Orit | Manzali, Sigalit | Heymann, Anthony | Beeri, Michal Schnaider

Article Type: Research Article

Abstract: Background: Family history of Alzheimer’s disease (AD) is associated with increased dementia-risk. Objective: The Israel Registry for Alzheimer’s Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH–) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. Methods: Participants are members of the Maccabi Health Services, 40–65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic …medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. Results: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n  = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH–. Compared to FH–, FH+ participants were younger (p  = 0.011), more often males (p  = 0.003) and with a higher prevalence of the APOE E4 allele (32.8% FH+, 22% FH–; p  = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH–in global cognition (p  = 0.027) and episodic memory (p  = 0.022). Conclusion: Lower cognitive scores and higher rates of the APOE E4 allele among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology. Show more

Keywords: Alzheimer’s disease, APOE E4, family history, offspring, risk factors

DOI: 10.3233/JAD-200623

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Chang, Kuo-Hsuan | Huang, Ching-Chang | Chen, Chiung-Mei | Wu, Hsiu-Chuan | Kuo, Hung-Chou

Article Type: Research Article

Abstract: Background: The behavioral and psychological symptoms of dementia (BPSD) seriously affect the quality of life of patients with Alzheimer’s disease (AD) and their caregivers. Objective: We aimed to identify associations between demographic/genetic factors and clinical presentations of BPSD. Methods: In a cohort of 463 AD patients with BPSD, we retrospectively analyzed sex, education level, AD severity (assessed using the Clinical Dementia Rating and Mini-Mental Status Examination), and BPSD severity (assessed using the Neuropsychiatry Inventory, NPI). Severe BPSD was defined as NPI ≥10 for 3 consecutive years. Results: Among patients with severe BPSD (NPI ≥10), …we observed more female patients (62.96%) and a lower level of education (6.03±4.77 years) as compared to those with mild BPSD (NPI <10) (female: 51.09%, p  = 0.007; education years: 7.91±4.93, p  <  0.001). Females had a lower level of education (5.72±4.50 years) and higher scores for depression/dysphoria (1.22±2.05) compared with males (education: 8.96±4.89 years, p  <  0.001; depression/dysphoria: 0.78±1.42, p  = 0.047). Patients with a high level of education (defined as ≥12 years) had higher scores for appetite/eating (0.90±2.02) than did those without (0.69±1.79; p  = 0.001). Genetic analysis showed similar total and subscale NPI scores between patients with and without APOE4 and with and without the GRN rs5848 genotype. Conclusion: Our findings indicate potential contributions of sex and education to the presentation of BPSD. Further study is warranted to provide models for tailoring therapeutic programs to individual AD patients according to these factors. Show more

Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, education level, Neuropsychiatric Inventory, sex

DOI: 10.3233/JAD-200507

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020