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

Authors: Calderón-Garcidueñas, Lilian | Torres-Jardón, Ricardo | Franco-Lira, Maricela | Kulesza, Randy | González-Maciel, Angélica | Reynoso-Robles, Rafael | Brito-Aguilar, Rafael | García-Arreola, Berenice | Revueltas-Ficachi, Paula | Barrera-Velázquez, Juana Adriana | García-Alonso, Griselda | García-Rojas, Edgar | Mukherjee, Partha S. | Delgado-Chávez, Ricardo

Article Type: Review Article

Abstract: Alzheimer’s and Parkinson’s diseases (AD, PD) have a pediatric and young adult onset in Metropolitan Mexico City (MMC). The SARS-CoV-2 neurotropic RNA virus is triggering neurological complications and deep concern regarding acceleration of neuroinflammatory and neurodegenerative processes already in progress. This review, based on our MMC experience, will discuss two major issues: 1) why residents chronically exposed to air pollution are likely to be more susceptible to SARS-CoV-2 systemic and brain effects and 2) why young people with AD and PD already in progress will accelerate neurodegenerative processes. Secondary mental consequences of social distancing and isolation, fear, financial insecurity, violence, …poor health support, and lack of understanding of the complex crisis are expected in MMC residents infected or free of SARS-CoV-2. MMC residents with pre-SARS-CoV-2 accumulation of misfolded proteins diagnostic of AD and PD and metal-rich, magnetic nanoparticles damaging key neural organelles are an ideal host for neurotropic SARS-CoV-2 RNA virus invading the body through the same portals damaged by nanoparticles: nasal olfactory epithelium, the gastrointestinal tract, and the alveolar-capillary portal. We urgently need MMC multicenter retrospective-prospective neurological and psychiatric population follow-up and intervention strategies in place in case of acceleration of neurodegenerative processes, increased risk of suicide, and mental disease worsening. Identification of vulnerable populations and continuous effort to lower air pollution ought to be critical steps. Show more

Keywords: ACE2, air pollution, Alzheimer’s disease, COVID 19, depression, nanoparticles, neurotropism, Parkinson’s disease, SARS-CoV-2, suicide

DOI: 10.3233/JAD-200891

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 479-503, 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. 78, no. 2, pp. 505-514, 2020

Authors: Rosin, Eric R. | Blasco, Drew | Pilozzi, Alexander R. | Yang, Lawrence H. | Huang, Xudong

Article Type: Review Article

Abstract: As the most common form of senile dementia, Alzheimer’s disease (AD) is accompanied by a great deal of uncertainty which can lead to fear and stigma for those identified with this devastating disease. As the AD definition evolves from a syndromal to a biological construct, and early diagnoses becomes more commonplace, more confusion and stigma may result. We conducted a narrative review of the literature on AD stigma to consolidate information on this body of research. From the perspective of several stigma theories, we identified relevant studies to inform our understanding of the way in which implementation of the new …framework for a biological based AD diagnosis may have resulted in new and emerging stigma. Herein, we discuss the emergence of new AD stigma as our understanding of the definition of the disease changes. We further propose recommendations for future research to reduce the stigma associated with AD. Show more

Keywords: Aging, Alzheimer’s disease, dementia, mild cognitive impairment, stigma, subjective cognitive impairment

DOI: 10.3233/JAD-200932

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 515-528, 2020

Authors: Walter, Marlena | Wiltfang, Jens | Vogelgsang, Jonathan

Article Type: Short Communication

Abstract: Previous studies on blood-based biomarkers for Alzheimer’s disease suggest a less invasive blood test might be a valuable screening tool for Alzheimer-specific pathology. Pre-analytical sample storage conditions seem to play an important role on amyloid-β (Aβ) stability, impacting reliability and reproducibility. This study shows that Aβ40 , Aβ42 , and Aβ42/40 levels significantly and early decrease during storage at room temperature in whole blood or plasma. Storing blood samples at 4°C leads to stable Aβ peptide concentrations up to 72 h. In addition, Aβ peptides can be measured in capillary blood with a stable Aβ42/40 ratio up to 72 h …at 4°C. Show more

Keywords: Alzheimer’s disease, amyloid-β , blood collection, blood storage, plasma biomarker

DOI: 10.3233/JAD-200777

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 529-535, 2020

Authors: Matias-Guiu, Jordi A. | Pytel, Vanesa | Matías-Guiu, Jorge

Article Type: Short Communication

Abstract: We aimed to evaluate the frequency and mortality of COVID-19 in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We conducted an observational case series. We enrolled 204 patients, 15.2% of whom were diagnosed with COVID-19, and 41.9% of patients with the infection died. Patients with AD were older than patients with FTD (80.36±8.77 versus 72.00±8.35 years old) and had a higher prevalence of arterial hypertension (55.8% versus 26.3%). COVID-19 occurred in 7.3% of patients living at home, but 72.0% of those living at care homes. Living in care facilities and diagnosis of AD were independently associated with a …higher probability of death. We found that living in care homes is the most relevant factor for an increased risk of COVID-19 infection and death, with AD patients exhibiting a higher risk than those with FTD. Show more

Keywords: Alzheimer’s disease, care homes, COVID-19, frontotemporal dementia, SARS-CoV-2

DOI: 10.3233/JAD-200940

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 537-541, 2020

Authors: Andreu-Reinón, María Encarnación | Huerta, José María | Gavrila, Diana | Amiano, Pilar | Mar, Javier | Tainta, Mikel | Ardanaz, Eva | Larumbe, Rosa | Navarro, Carmen | Colorado-Yohar, Sandra M. | Navarro-Mateu, Fernando | Chirlaque, María Dolores

Article Type: Research Article

Abstract: Background: Dementia has become a public health priority as the number of cases continues to grow worldwide. Objective: To assess dementia incidence and determinants in the EPIC-Spain Dementia Cohort. Methods: 25,015 participants (57% women) were recruited from three Spanish regions between 1992-1996 and followed-up for over 20 years. Incident cases were ascertained through individual revision of medical records of potential cases. Crude and age-adjusted incidence rates (IR) of dementia and sub-types (Alzheimer’s disease (AD), and non-AD) were calculated by sex. Neelson-Aalen cumulative incidence estimates at 10, 15, and 20 years were obtained for each sex and …age group. Multivariate Royston-Parmar models were used to assess independent determinants. Results: Global IR were higher in women for dementia and AD, and similar by sex for non-AD. IR ranged from 0.09 cases of dementia (95% confidence interval: 0.06–0.13) and 0.05 (0.03–0.09) of AD per 1000 person-years (py) in participants below 60 years, to 23.2 (15.9–33.8) cases of dementia and 14.6 (9.1–33.5) of AD (per 1000 py) in those ≥85 years. Adjusted IR were consistently higher in women than men for overall dementia and AD. Up to 12.5% of women and 9.1% of men 60–65 years-old developed dementia within 20 years. Low education, diabetes, and hyperlipidemia were the main independent predictors of dementia risk, whereas alcohol showed an inverse association. Conclusion: Dementia incidence increased with age and was higher among women, but showed no geographical pattern. Dementia risk was higher among subjects with lower education, not drinking alcohol, and presenting cardiovascular risk factors. Show more

Keywords: Alzheimer’s disease, cohort study, dementia, EPIC-Spain, epidemiology, incidence, risk factors

DOI: 10.3233/JAD-200774

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 543-555, 2020

Authors: Hauer, Klaus | Schwenk, Michael | Englert, Stefan | Zijlstra, Rixt | Tuerner, Sabine | Dutzi, Ilona

Article Type: Research Article

Abstract: Background: Match or mismatch of objective physiological and subjectively perceived fall risk may have serious consequences in patients with dementia (PwD) while research is lacking. Objective: To analyze mismatch of objective and subjective fall risk and associated factors in PwD. Method: Cohort study in a geriatric rehabilitation center. Objective and subjective risk of falling were operationalized by Tinetti’s Performance Oriented Mobility Assessment and the Falls Efficacy Scale-International. Four sub-groups according to objective and subjective fall risk were classified. Subgroups were compared for differences in clinical, cognitive, psychological, and behavioral variables. Results: In geriatric rehab …patients with mild to moderate dementia (n  = 173), two-thirds showed a mismatch of subjective versus objective risk of falling, independently associated with previous falls. Underestimation of objective fall risk (37.6%) was determined by lower activity avoidance (OR 0.39), less concerns about falling due to previous falls (OR 0.25), and higher quality of life (OR 1.10), while overestimation (28.9%) was determined by higher rate of support seeking strategies (OR 50.3), activity avoidance (OR 15.2), better executive (OR 21.0) and memory functions (OR 21.5), and lower quality of life (OR.75) in multivariate logistic regression. Conclusion: The majority of patients showed a mismatch between objective and subjective falls risk. Underestimation as well as overestimation of fall risk was associated with specific profiles based on cognitive- and psychological status, falls and fall-related behavioral consequences which should be included in the comprehensive assessment of fall risk, and planning of individualized fall prevention programs for this population. Show more

Keywords: Cognitive impairment, dementia, elderly, fall risk, falls, fear of falling

DOI: 10.3233/JAD-200572

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 557-572, 2020

Authors: Jang, Hyemin | Kim, Hee Jin | Choe, Yeong Sim | Kim, Soo-Jong | Park, Seongbeom | Kim, Yeshin | Kim, Ko Woon | Lyoo, Chul Hyoung | Cho, Hanna | Ryu, Young Hoon | Choi, Jae Yong | DeCarli, Charles | Na, Duk L. | Seo, Sang Won | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: As Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) commonly coexist, the interaction between two has been of the considerable interest. Objective: We determined whether the association of Aβ and tau with cognitive decline differs by the presence of significant CSVD. Methods: We included 60 subcortical vascular cognitive impairment (SVCI) from Samsung Medical Center and 82 Alzheimer’s disease-related cognitive impairment (ADCI) from ADNI, who underwent Aβ (florbetaben or florbetapir) and tau (flortaucipir, FTP) PET imaging. They were retrospectively assessed for 5.0±3.9 and 5.6±1.9 years with Clinical Dementia Rating-sum of boxes (CDR-SB)/Mini-Mental State Examination (MMSE). …Mixed effects models were used to investigate the interaction between Aβ/tau and group on CDR-SB/MMSE changes. Results: The frequency of Aβ positivity (45% versus 54.9%, p  = 0.556) and mean global FTP SUVR (1.17±0.21 versus 1.16±0.17, p  = 0.702) were not different between the two groups. We found a significant interaction effect of Aβ positivity and SVCI group on CDR-SB increase/MMSE decrease (p  = 0.013/p  < 0.001), and a significant interaction effect of global FTP uptake and SVCI group on CDR-SB increase/MMSE decrease (p  < 0.001 and p  = 0.030). Finally, the interaction effects of regional tau and group were prominent in the Braak III/IV (p  = 0.001) and V/VI (p  = 0.003) not in Braak I/II region (p  = 0.398). Conclusion: The association between Aβ/tau and cognitive decline is stronger in SVCI than in ADCI. Therefore, our findings suggested that Aβ positivity or tau burden (particularly in the Braak III/IV or V/VI regions) and CSVD might synergistically affect cognitive decline. Show more

Keywords: Alzheimer’s disease, amyloid, cerebral small vessel diseases, cognitive dysfunction, positron emission tomography, tau, vascular dementia

DOI: 10.3233/JAD-200680

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 573-585, 2020

Authors: Cardoso, Remy | Lemos, Carolina | Oliveiros, Bárbara | Almeida, Maria Rosário | Baldeiras, Inês | Pereira, Cláudia Fragão | Santos, Ana | Duro, Diana | Vieira, Daniela | Santana, Isabel | Oliveira, Catarina Resende

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer’s disease (AD) conversion remain controversial. Objective: Evaluate whether TOMM40 poly-T (TOMM40 ′ 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. Methods: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those …that remained stable (MCI-S). Results: TOMM40 ′ 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p  < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOE ɛ 4 allele, both the L allele and ɛ 4 allele lost significance in the model (p  > 0.05). We then analyzed the APOE ɛ 4-TOMM40′ 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30–14.83) and mean lower times of conversion to AD (p  = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p  = 0.007). Conclusion: This study shows that the APOE ɛ 4-TOMM40′ 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction. Show more

Keywords: Age of onset, Alzheimer’s disease, APOE , biomarker, cerebrospinal fluid, haplotype, mild cognitive impairment, poly T, progression, TOMM40

DOI: 10.3233/JAD-200556

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 587-601, 2020

Authors: Ashby-Mitchell, Kimberly | Willie-Tyndale, Douladel | Eldemire-Shearer, Denise

Article Type: Research Article

Abstract: Background: Dementia has no known cure and age is its strongest predictor. Given that populations in the Caribbean are aging, a focus on policies and programs that reduce the risk of dementia and its risk factors is required. Objective: To estimate the proportion of dementia in the Jamaican setting attributable to key factors. Methods: We analyzed the contribution of five modifiable risk factors to dementia prevalence in Jamaica using a modified Levin’s Attributable Risk formula (low educational attainment, diabetes, smoking status, depression, and physical inactivity). Four sources of data were used: risk factor prevalence was obtained …from the Jamaica Health and Lifestyle Survey, 2008, relative risk data were sourced from published meta-analyses, shared variance among risk factors was determined using cross-sectional data from the Health and Social Status of Older Persons in Jamaica Study. Estimated future prevalence of dementia in Jamaica was sourced from a published ADI/BUPA report which focused on dementia in the Americas. We computed the number of dementia cases attributable to each risk factor and estimated the effect of a reduction in these risk factors on future dementia prevalence. Results: Accounting for the overlapping of risk factors, 34.46% of dementia cases in Jamaica (6548 cases) were attributable to the five risk factors under study. We determined that if each risk factor were to be reduced by 5% –10% per decade from 2010–2050, dementia prevalence could be reduced by up to 14.0%. Conclusion: As the risk factors for dementia are shared with several of the main causes of death in Jamaica, a reduction in risk factors by even 5% can result in considerable public health benefit. Show more

Keywords: Caribbean, dementia, Jamaica, low and middle-income countries, population attributable risk

DOI: 10.3233/JAD-200601

Citation: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 603-609, 2020