Journal of Alzheimer's Disease - Volume 78, issue 2

Authors: Xu, Zhongzhi | Yang, Jiannan | Lau, Kui Kai | Yip, Paul S.F. | Wong, Ian C.K. | Zhang, Qingpeng

Article Type: Research Article

Abstract: Background: Given concerns about adverse outcomes for older people taking antidepressants in the literature, we investigated whether taking antidepressants elevates the risk of dementia. Objective: This study aims to investigate the putative association of antidepressants with the risk of dementia. Methods: We conducted a population-based self-controlled case series analysis of older people with dementia and taking antidepressants, using territory-wide medical records of 194,507 older patients collected by the Hospital Authority of Hong Kong, to investigate the association between antidepressant treatment and the risk of developing dementia in older people. Results: There was a significantly …higher risk of being diagnosed with dementia during the pre-drug-exposed period (incidence rate ratio (IRR) 20.42 (95% CI: 18.66–22.34)) compared to the non-drug-exposed baseline period. The IRR remained high during the drug-exposed period (IRR 8.86 (7.80–10.06)) before returning to a baseline level after washout (IRR 1.12 (0.77–1.36)). Conclusion: The higher risk of dementia before antidepressant treatment may be related to emerging psychiatric symptoms co-occurring with dementia, which trigger medical consultations that result in a decision to begin antidepressants. Our findings do not support a causal relationship between antidepressant treatment and the risk of dementia. Show more

Keywords: Alzheimer’s disease, antidepressants, causal associations, dementia, self-controlled case series studies

DOI: 10.3233/JAD-200875

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 735-744, 2020

Authors: Lee, Jun Ho | Byun, Min Soo | Yi, Dahyun | Ko, Kang | Jeon, So Yeon | Sohn, Bo Kyung | Lee, Jun-Young | Lee, Younghwa | Joung, Haejung | Lee, Dong Young | for the KBASE Research Group

Article Type: Research Article

Abstract: Background: Previous studies indicated an association between Alzheimer’s disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10μ m (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association. Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging. Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11 C-Pittsburg compound B …(PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18 F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10μ m over the past 5 years (PM10mean ) collected from air pollution surveillance stations were matched to each participant’s residence. Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure. Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition. Show more

Keywords: Amyloid-β, cognitively normal, mild cognitive impairment, neurodegeneration, PM10, tau

DOI: 10.3233/JAD-200694

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 745-756, 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. 78, no. 2, pp. 757-775, 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 carriers (32.9% 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 carriers 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. 78, no. 2, pp. 777-788, 2020

Authors: Crocco, Elizabeth | Curiel-Cid, Rosie E. | Kitaigorodsky, Marcela | González-Jiménez, Christian J. | Zheng, Diane | Duara, Ranjan | Loewenstein, David A.

Article Type: Research Article

Abstract: Background: The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is an increasingly utilized cognitive stress test designed to identify early cognitive changes associated with incipient neurodegenerative disease. Objective: To examine previously derived cut-points for cognitively unimpaired older adults that were suggestive of performance impairment on multiple subscales of the LASSI-L. These cut-points were applied to a new sample of older adults who were cognitive healthy controls (HC: n  = 26) and those on the Alzheimer’s disease (AD) continuum from early stage mild cognitive impairment (EMCI: n  = 28), late stage MCI (LMCI: n = 18) to mild AD …(AD: n  = 27). Methods: All participants were administered the LASSI-L. All cognitively impaired participants were PET amyloid positive which likely reflects underlying AD neuropathology, while cognitively normal counterparts were deemed to have amyloid negative scans. Results: There was a monotonic relationship between the number of deficits on LASSI-L subscales and independent classification of study groups with greater severity of cognitive impairment. Importantly, taken together, impairment on maximum learning ability and measures of proactive semantic interference (both reflected by cued recall and intrusion errors) correctly classified 74.1% of EMCI, 94.4% of LMCI, and 96.3% of AD. Only 7.7% of HC were incorrectly classified as having impairments. Conclusion: A modest number of LASSI-L subscales taking approximately 8 minutes to administer, had excellent discriminative ability using established cut-offs among individuals with presumptive stages of AD. This has potential implications for both clinical practice and clinical research settings targeting AD during early prodromal stages. Show more

Keywords: Amyloid, biomarkers, cognitive screening, intrusion errors, mild cognitive impairment, neuroimaging, preclinical Alzheimer’s disease, semantic interference, structural MRI

DOI: 10.3233/JAD-200790

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 789-799, 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. 78, no. 2, pp. 801-817, 2020

Authors: Menne, Felix | Schipke, Carola Gertrud | Klostermann, Arne | Fuentes-Casañ, Manuel | Freiesleben, Silka Dawn | Bauer, Chris | Peters, Oliver

Article Type: Research Article

Abstract: Background: Depressive symptoms often co-occur with Alzheimer’s disease (AD) and can impact neuropsychological test results. In early stages of AD, disentangling cognitive impairments due to depression from those due to neurodegeneration often poses a challenge. Objective: We aimed to identify neuropsychological tests able to detect AD-typical pathology while taking into account varying degrees of depressive symptoms. Methods: A battery of neuropsychological tests (CERAD-NP) and the Geriatric Depression Scale (GDS) were assessed, and cerebrospinal fluid (CSF) biomarkers were obtained. After stratifying patients into CSF positive or negative and into low, moderate, or high GDS score groups, sensitivity …and specificity and area under the curve (AUC) were calculated for each subtest. Results: 497 participants were included in the analyses. In patients with low GDS scores (≤10), the highest AUC (0.72) was achieved by Mini-Mental State Examination, followed by Constructional Praxis Recall and Wordlist Total Recall (AUC = 0.714, both). In patients with moderate (11–20) and high (≥21) GDS scores, Trail Making Test-B (TMT-B) revealed the highest AUCs with 0.77 and 0.82, respectively. Conclusion: Neuropsychological tests showing AD-typical pathology in participants with low GDS scores are in-line with previous results. In patients with higher GDS scores, TMT-B showed the best discrimination. This indicates the need to focus on executive function rather than on memory task results in depressed patients to explore a risk for AD. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, depression, executive function, memory, neuropsychology

DOI: 10.3233/JAD-200710

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 819-826, 2020

Authors: Hu, Emily A. | Wu, Aozhou | Dearborn, Jennifer L. | Gottesman, Rebecca F. | Sharrett, A. Richey | 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. 78, no. 2, pp. 827-835, 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 β1 “TGF-β1”). 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-β1 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-β1 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-β1, and to be stronger in AD than the other groups. Conclusion: Measurements of P300 latency and serum levels of TGF-β1 can help distinguish AD, PDD, and VaD. P300 was more prolonged in AD and PDD than VaD whereas TGF-β1 was significantly higher in AD and VaD than PDD. Thus P300 and TGF-β1 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. 78, no. 2, pp. 837-845, 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. 78, no. 2, pp. 847-852, 2020