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

Authors: Richard Chen, X. | Shao, Yongzhao | Sadowski, Martin J. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: APOE ɛ 4 allele carriers present with increased risk for late-onset Alzheimer’s disease (AD), show cognitive symptoms at earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ 4 allele controls the rate of disease progression. Objective: To determine effects of the ɛ 4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD. Methods: A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of …73 ɛ 3/ɛ 3, 99 ɛ 3/ɛ 4, and 39 ɛ 4/ɛ 4 Alzheimer’s Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia. Results: ɛ 4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ 4 allele-dose effects after dementia transition but not during MCI. The ɛ 4 effect was more prevalent in younger participants and in females. ɛ 4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI. Conclusion: Possession of the ɛ 4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design. Show more

Keywords: Alzheimer disease, APOE, cognitive decline, linear mixed model, MRI

DOI: 10.3233/JAD-210434

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2021

Authors: Ancelin, Marie-Laure | Norton, Joanna | Scali, Jacqueline | Ritchie, Karen | Chaudieu, Isabelle | Ryan, Joanne

Article Type: Short Communication

Abstract: Diurnal salivary cortisol was measured in 334 older adults without dementia, at four times on two separate days, under quiet and stressful conditions. In multivariate Cox proportional hazard models, higher global diurnal cortisol secretion was associated with incident dementia (HR = 1.09 [1.02–1.15] per one-unit increase in cortisol measure, p  = 0.007) and Alzheimer’s disease (HR = 1.12 [1.04–1.21], p  = 0.003) over a mean(SD) of 8.1(4.0) years, independent of potential confounders and stressful conditions. Individuals with incident dementia had a slower rate of cortisol elimination under non-stressful conditions, reflected by higher cortisol levels in the evening, and an abnormal response to stress (blunted evening stress …response). Show more

Keywords: Cortisol, dementia, hypothalamic-pituitary-adrenal axis, prospective study, stress

DOI: 10.3233/JAD-210389

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2021

Authors: Covatti Malcorra, Bárbara Luzia | Mota, Natália Bezerra | Weissheimer, Janaina | Schilling, Lucas Porcello | Wilson, Maximiliano Agustin | Hübner, Lilian Cristine

Article Type: Short Communication

Abstract: Connected speech is an everyday activity. We aimed to investigate whether connected speech can differentiate oral narrative production between adults with Alzheimer’s disease (AD; n  = 24) and cognitively healthy older adults (n  = 48). We used graph attributes analysis to represent connected speech. Participants produced oral narratives and performed semantic, episodic, and working memory tasks. AD patients produced less connected narratives than cognitively healthy older adults. Connectedness was associated with semantic memory in AD and with episodic memory in controls. Word-graphs connectedness represents a practical tool to assess cognitive impairment in AD patients.

Keywords: Alzheimer’s disease, cognitive decline, graph theory, natural language processing, semantic memory

DOI: 10.3233/JAD-210134

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2021

Authors: Spera, Vincenza | Sitnikova, Tatiana | Ward, Meredith J. | Farzam, Parya | Hughes, Jeremy | Gazecki, Samuel | Bui, Eric | Maiello, Marco | De Taboada, Luis | Hamblin, Michael R. | Franceschini, Maria Angela | Cassano, Paolo

Article Type: Research Article

Abstract: Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Methods: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy …subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2 ; 65.8 J/cm2 ; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2 ; 33%; 21.7 J/cm2 ; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. Results: c-tPBM significantly boosted gamma (t  = 3.02, df = 7, p  <  0.02) and beta (t  = 2.91, df = 7, p  <  0.03) EEG spectral powers in eyes-open recordings and gamma power (t  = 3.61, df = 6, p  <  0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. Conclusion: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR. Show more

Keywords: Cerebral blood flow, EEG oscillations, light-emitting diode, photobiomodulation, transcranial light therapy, transcranial near-infrared light

DOI: 10.3233/JAD-210058

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2021

Authors: Zhao, Xuan | Li, Cancan | Ding, Guoyong | Heng, Yuanyuan | Li, An | Wang, Wei | Hou, Haifeng | Wen, Jun | Zhang, Yanbo

Article Type: Research Article

Abstract: Background: The increasing prevalence of Alzheimer’s disease (AD), along with the associated burden on healthcare systems, presents a substantial public health challenge. Objective: This study aimed to investigate trends in AD mortality and the relevant burden across the United States (U.S.) from 1999 to 2018 and to predict mortality trends between 2019 and 2023. Methods: Data on AD-related deaths between 1999 and 2018 were collected from the WONDER database administered by the U.S. Centers for Disease Control and Prevention (CDC). The Joinpoint Regression Program was used to analyze mortality trends due to AD. Years of life …lost (YLL) were calculated to explore the burden of AD deaths. An autoregressive integrated moving average (ARIMA) model was employed to forecast mortality trends from 2019 to 2023. Results: Over a recent 20-year period, the number of AD deaths in the U.S. increased from 44,536 (31,145 females and 13,391 males) to 122,019 (84,062 females and 37,957 males). The overall age-adjusted mortality rate increased from 16.5/100,000 in 1999 to 30.5/100,000 in 2018. AD mortality is projected to reach 42.40/100000 within the year 2023. Overall, AD resulted in 322,773.00 YLL (2.33 per 1000 population) in 1999 and 658,501.87 YLL (3.68 per 1000 population) in 2018. Conclusion: Our findings demonstrate an increase in AD mortality in the U.S. from 1999 to 2018 as well as a rapid increase from 2019 to 2023. The high burden of AD deaths emphasizes the need for targeted prevention, early diagnosis, and hierarchical management. Show more

Keywords: Alzheimer’s disease, mortality, time series analysis, years of life lost

DOI: 10.3233/JAD-210225

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Paradela, Regina Silva | Ferreira, Naomi Vidal | Nucci, Mariana Penteado | Cabella, Brenno | Martino, Luiza Menoni | Torres, Laura Aló | Costa, Danielle Irigoyen da | Consolim-Colombo, Fernanda Marciano | Suemoto, Claudia Kimie | Irigoyen, Maria Claudia

Article Type: Research Article

Abstract: Background: Socioeconomic factors are important contributors to brain health. However, data from developing countries (where social inequalities are the most prominent) are still scarce, particularly about hypertensive individuals. Objective: To evaluate the relationship between socioeconomic index, cognitive function, and cortical brain volume, as well as determine whether white matter hyperintensities are mediators of the association of the socioeconomic index with cognitive function in hypertensive individuals. Methods: We assessed 92 hypertensive participants (mean age = 58±8.6 years, 65.2%female). Cognitive evaluation and neuroimaging were performed and clinical and sociodemographic data were collected using questionnaires. A socioeconomic index was created using …education, income, occupation (manual or non-manual work), and race. The associations of the socioeconomic index with cognitive performance and brain volume were investigated using linear regression models adjusted for age, sex, time of hypertension since diagnosis, and comorbidities. A causal mediation analysis was also conducted. Results: Better socioeconomic status was associated with better visuospatial ability, executive function, and global cognition. We found associations between a better socioeconomic index and a higher parietal lobe volume. White matter hyperintensities were also not mediators in the relationship between the socioeconomic index and cognitive performance. Conclusion: Socioeconomic disadvantages are associated with worse cognitive performance and brain volume in individuals with hypertension. Show more

Keywords: Brain volume, cognitive dysfunction, executive function, hypertension, neuroimaging, social determinants of health, white matter hyperintensities

DOI: 10.3233/JAD-210143

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Schoemaker, Dorothee | Velilla, Lina | Zuluaga, Yesica | Baena, Ana | Ospina, Carolina | Bocanegra, Yamile | Alvarez, Sergio | Ochoa-Escudero, Martin | Guzmán-Vélez, Edmarie | Martinez, Jairo | Lopera, Francisco | Arboleda-Velasquez, Joseph F. | Quiroz, Yakeel T.

Article Type: Research Article

Abstract: Background: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer’s disease and vascular dementia. Objective: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer’s disease and vascular dementia. Methods: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer’s disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts …and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. Results: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = –0.06, p  <  0.05) and an increased severity of cerebral microbleeds (B = 0.13, p  <  0.001), lacunes (B = 0.30, p  <  0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p  <  0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p  <  0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. Conclusion: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks. Show more

Keywords: Autosomal dominant Alzheimer’s disease, CADASIL, cardiovascular risk factors, cerebral small vessel disease, cognition, magnetic resonance imaging

DOI: 10.3233/JAD-210313

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Bullock-Saxton, Joanne | Lehn, Alexander | Laakso, E-Liisa

Article Type: Research Article

Abstract: Background: Neuroprotection against Parkinson’s disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. Objective: To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson’s disease; and what frequency of treatment is necessary to initiate clinical change. Methods: In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for …4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. Results: Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. Conclusion: The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required. Show more

Keywords: Cognition, Parkinson’s disease, photobiomodulation, physical functional performance

DOI: 10.3233/JAD-210170

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Rao, K.S. Jagannatha | Britton, Gabrielle | Rocha Arrieta, Luisa Lilia | Garcia-Cairasco, Norberto | Lazarowski, Alberto | Palacios, Adrián | Camins Espuny, Antoni | Maccioni, Ricardo B.

Article Type: Research Article

DOI: 10.3233/JAD-210245

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-4, 2021

Authors: Sewell, Margaret C. | Neugroschl, Judith | Umpierre, Mari | Chin, Shehan | Zhu, Carolyn W. | Velasco, Nelly | Gonzalez, Sabrina | Acabá-Berrocal, Alexandra | Bianchetti, Luca | Silva, Gabriela | Collazo, Alma | Sano, Mary

Article Type: Research Article

Abstract: Background: Latinx elders are underrepresented in dementia research. In a previous study we assessed research attitudes in urban minority elders and found a significant minority expressed neutral to negative attitudes relating to trust, safety, and personal responsibility to help research. Objective: To assess the impact of a composite intervention on attitudes toward research and research participation among elderly Latinx. The intervention was a collaboratively produced research participation video shown during presentations with our elderly community advisory board (CAB) as co-presenters. Methods: The video was created by the ADRC and CAB. All senior center attendees were eligible …to participate. Afterwards, the Research Attitudes Questionnaire (RAQ) and a brief questionnaire on the impact of the video were administered. Using Wilcoxon Rank Sum Tests, Chi Square, and OLS regressions, RAQ responses were compared to those from a historical cohort from similar centers. Results: 74 in the “Historical Cohort 1” and 104 in “Intervention Cohort 2” were included. RAQ total score was higher in Cohort 2 than Cohort 1 (28.5 versus 26.1, p  <  0.05) after controlling for age, education, and country of origin. In response to the question “Has the video influenced your willingness and interest to participate in research”, 88.7%of the participants in Cohort 2 reported being “more” or “much more” interested in research. Conclusion: Tailoring community research recruitment programs to include relatable peers using novel recruitment techniques may have positive implications for improving enrollment of diverse elderly individuals in research. Show more

Keywords: Attitudes towards research, diversity, elder minorities, minorities in research, research participation

DOI: 10.3233/JAD-210027

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2021