Journal of Alzheimer's Disease - Volume 84, issue 2

Authors: Dutzi, Ilona | Schwenk, Michael | Kirchner, Marietta | Jooss, Eva | Bauer, Jürgen M. | Hauer, Klaus

Article Type: Research Article

Abstract: Background: Cognitive impairment (CI) has been reported to negatively impact rehabilitation outcomes. Knowledge about differences in rehabilitation received in dependence of CI as a potential mediating factor is limited. Objective: To analyze whether CI affects amount and frequency of rehabilitation received and if associations between CI and rehabilitation outcome are mediated by the provided amount of therapy. Methods: Observational cohort study in ward-based geriatric rehabilitation consecutively including 373 patients (mean age 82.0±6.69 years, mean MMSE 23.66±5.31). Outcome measures were amount, frequency, and type of multi-professional therapy sessions and rehabilitation outcome assessed with the Barthel Index (BI). …Cognitive status was measured with the Mini-Mental-State Examination (MMSE) classifying three patient subgroups according to cognitive status. Results: Patients with more severe CI received least total therapy hours (TTH) (MMSE < 17, 13.67±6.58 versus MMSE 17–26, 16.12±7.19 and MMSE > 26, 17.79±8.88 h, p  = 0.014) and were less often included in occupational therapy (MMSE < 17, 48.9%versus MMSE 17–26, 65.5%and MMSE > 26, 71.4%, p  = 0.019) and group-based physiotherapy (MMSE < 17, 73.3%versus MMSE 17–26, 88.5%and MMSE > 26, 81.2%, p  = 0.027). Regression models showed that CI negatively impacted TTH (β= 0.24, p  = 0.003) and rehabilitation outcome (β= 0.41, p  = 0.008). In the mediation model, TTH accounted for 23.18%(p  < 0.001) of the relationship between CI and rehabilitation outcome. Conclusion: Cognitive impairment negatively impacted rehabilitation received. The lower TTH partly mediated the negative association between CI and rehabilitation outcome. Future research should identify specific barriers to therapy provision and optimal length, intensity, and dosage of rehabilitation programs to optimize rehabilitation outcomes in CI. Show more

Keywords: Cognitive impairment, functional outcome, rehabilitation, therapy provision

DOI: 10.3233/JAD-210620

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 745-756, 2021

Authors: Palermo, Giovanni | Belli, Elisabetta | Tommasini, Luca | Morganti, Riccardo | Frosini, Daniela | Nicoletti, Valentina | Tognoni, Gloria | Siciliano, Gabriele | Bonuccelli, Ubaldo | Baldacci, Filippo | Ceravolo, Roberto

Article Type: Research Article

Abstract: Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are differentiated by the time of onset of cognitive and motor symptoms (‘1-year rule’). We explored the neuropsychological continuum of DLB and PDD subjects with different timing of dementia onset. Objective: Our aim was to compare the neuropsychological profile of DLB and PDD patients with different timing of dementia onset. Methods: Neuropsychological findings at the diagnosis of dementia of 66 PDD and 42 DLB patients were retrospectively compared. Patients with PDD were divided into three tertile subgroups according to the time interval between the onset …of parkinsonism and dementia (N  = 24, 2–4 years; N  = 17, 5–7 years; N  = 25 ≥8 years, respectively). Results: DLB patients performed worse on the Stroop and semantic fluency tests than PDD, even in comparison to PD with early dementia onset. No significant differences among PDD subgroups were reported. Conclusion: Executive and semantic language tests could differentiate DLB and PD patients with earlier development of dementia relative to parkinsonism. Show more

Keywords: Cognitive testing, dementia with Lewy bodies, Parkinson’s disease, ‘1-year rule’

DOI: 10.3233/JAD-210006

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 757-766, 2021

Authors: Heggy, Alaa | Masoumi, Aisha | Al-Yafei, Maryam | Al-Bader, Fatima | Al-Abdi, Tamara | Shi, Zumin

Article Type: Research Article

Abstract: Background: Tea and coffee consumption is associated with cognitive function in some studies. Objective: We aimed to identify tea and coffee drinking patterns and their association with mean reaction time among Qatari adults. Method: The study included 1,000 adults aged 20 years and above attending the Qatar Biobank Study (QBB). Habitual tea and coffee consumption during the previous year was assessed by questionnaire. Tea and coffee drinking patterns were identified using factor analysis. In a computer-based self-administered touch screens test, mean reaction time (MRT) was used as an indicator of cognitive function. Results: The …mean age of the participants was 35.8 (SD 10.3) years. Herbal tea and regular coffee consumption was inversely associated with MRT. In the multivariable model, compared with non-consumers, the regression coefficients for MRT were –34.3 (–65.4, –3.3) and –37.9 (–71.0, –4.7) for daily consumers of herbal tea and regular coffee, respectively. Of the two tea and coffee drinking patterns identified, pattern 1 (high consumption of tea, Arabic coffee, and herbal tea) was not associated with MRT but pattern 2 (high loadings of instant coffee, regular coffee, and Karak) was inversely associated with MRT in the unadjusted model. There was a significant interaction between pattern 2 and low-density lipoprotein (LDL) in relation to MRT. Pattern 2 was inversely associated with MRT among those with a low LDL. Conclusion: There was an inverse association between regular coffee and herbal tea consumption with mean reaction time. There was an interaction between Western coffee pattern and LDL. Show more

Keywords: Coffee, cognition, mean reaction time, Qatar biobank, tea

DOI: 10.3233/JAD-215130

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 767-776, 2021

Authors: Lan, Yu-Tung | Blacker, Deborah | Yuan, Changzheng | Chibnik, Lori B. | Hofman, Albert | Ma, Yuan

Article Type: Research Article

Abstract: Background: The evidence regarding dementia and late-life weight change is inconsistent, and data on body weight fluctuation and dementia are limited. Objective: To test the hypothesis that weight loss and substantial weight fluctuation predict cognitive decline independent of body weight and traditional risk factors of dementia. Methods: This study utilized longitudinal data from the National Alzheimer’s Coordinating Center for 10,639 stroke- and dementia-free older adults (60.9%female, mean age 71.6 years, median follow-up 5.5 years). Trends in weight change and weight fluctuation were estimated for each individual by regressing repeated body weight measurements on time. Cognitive decline …was examined as diagnostic progression from normal to mild cognitive impairment (MCI) or dementia and from MCI to dementia. Results: Compared to participants with stable weight, those with weight loss had increased odds of diagnostic progression (adjusted OR = 1.35, 95%CI [1.21, 1.51 ]). Also, large weight fluctuation was associated with increased odds of diagnostic progression (OR comparing the extreme quartiles = 1.20, 95%CI [1.04, 1.39 ]) after adjusting for traditional risk factors for dementia and body weight change. The magnitude of the association appeared larger among those older than 80 and those with 3 or more cardiometabolic risk factors at baseline (both p for interaction < 0.05). Conclusion: Weight loss and substantial weight fluctuation during late-life were associated with increased odds of cognitive decline independent of body weight and traditional risk factors of dementia. Our results suggested the linkage between late-life body weight instability and cognitive decline especially among those with greater age or higher cardiometabolic risk. Show more

Keywords: Alzheimer’s disease, body weight, dementia, epidemiology

DOI: 10.3233/JAD-210625

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 777-786, 2021

Authors: Matsuzono, Kosuke | Suzuki, Masayuki | Miura, Kumiko | Ozawa, Tadashi | Mashiko, Takafumi | Koide, Reiji | Tanaka, Ryota | Fujimoto, Shigeru

Article Type: Research Article

Abstract: Background: Many issues persist in the today’s Alzheimer’s disease (AD) screening and the breakthrough method is desired. Objective: We aim to validate the association between venous reflux and AD, and to develop a new method for AD screening. Methods: We examined spontaneous echo contrast, area, diameter, retrograde velocity, and anterograde velocity of the bilateral cervical internal jugular vein (IJV) using carotid ultrasonography. Results: A total of 112 patients participated in this study, with 26 diagnosed as AD. The proportion of both or either IJV spontaneous echo contrast (+) occupied 25 …of total 26 AD patients, which showed 96.2%of sensitivity and 98.5%negative predictive value. The IJV velocities also showed significant correlation with AD diagnosis, although the IJV area or diameter did not. Conclusion: Our results indicate that the validation of the spontaneous echo contrast or velocities of the IJV are convenient AD diagnosis screening methods and that the venous reflux disturbance correlates with AD development. Show more

Keywords: Alzheimer’s disease, atrial fibrillation, carotid ultrasonography, screening, venous reflux

DOI: 10.3233/JAD-210490

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 787-796, 2021

Authors: Fink, Anne | Doblhammer, Gabriele | Tamgüney, Gültekin

Article Type: Research Article

Abstract: Background: Gastrointestinal infections cause significant health problems, including those affecting the immune, musculoskeletal, and nervous system, and are one of the leading causes for death worldwide. Recent findings suggest that microbiota of the gastrointestinal tract contribute to dementia. Objective: In this nested case-control study we investigated the role of common gastrointestinal infections on the subsequent risk of dementia. Methods: We used a longitudinal sample of 202,806 individuals from health claims data of the largest German health insurer and applied a nested case-control design with 23,354 initial dementia cases between 2006 and 2014 and …23,354 matched controls. We used conditional logistic regression to compute odds ratios (ORs) for dementia and corresponding 95%confidence intervals (CIs), adjusting for potential confounders. Results: The risk of dementia was increased in patients with recurring incidences of quarters with diagnosed gastrointestinal infections when compared to the unexposed population (one quarter: OR = 1.49, 95%CI = 1.40–1.58; two quarters: OR = 1.70, 95%CI = 1.51–1.91; three or more quarters: OR = 1.64, 95%CI = 1.40–1.93), adjusted for potential confounders. Conclusion: Our findings suggest that recurring gastrointestinal infections are associated with an increased risk of subsequent dementia. Show more

Keywords: Alzheimer’s disease, dementia, gastrointestinal microbiome, risk

DOI: 10.3233/JAD-210316

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 797-806, 2021

Authors: Fukuda, Haruhisa | Ono, Rei | Maeda, Megumi | Murata, Fumiko

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) can increase both medical care and long-term care (LTC) costs, but the latter are frequently neglected in estimates of AD’s economic burden. Objective: To elucidate the economic burden of new AD cases in Japan by estimating patient-level medical care and LTC expenditures over 3 years using a longitudinal database. Methods: The study was performed using monthly claims data from residents of 6 municipalities in Japan. We identified patients with new AD diagnoses between April 2015 and March 2016 with 3 years of follow-up data. Medical care and LTC expenditures were estimated from …1 year before onset until 3 years after onset. To quantify the additional AD-attributable expenditures, AD patients were matched with non-AD controls using propensity scores, and their differences in expenditures were calculated. Results: After propensity score matching, the AD group and non-AD group each comprised 1748 individuals for analysis (AD group: mean age±standard deviation, 81.9±7.6 years; women, 66.0%). The total additional expenditures peaked at $1398 in the first month, followed by $1192 and $1031 in the second and third months, respectively. The additional LTC expenditures increased substantially 3 months after AD onset ($227), and gradually increased thereafter. These additional LTC expenditures eventually exceeded the additional medical care expenditures in the second year after AD onset. Conclusion: Although total AD-attributable expenditures peaked just after disease onset, the impact of LTC on these expenditures rose over time. Failure to include LTC expenditures would severely underestimate the economic burden of AD. Show more

Keywords: Alzheimer’s disease, dementia, health expenditures, healthcare administrative claims, long-term care

DOI: 10.3233/JAD-201508

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 807-817, 2021

Authors: Fischer, Corinne E. | Churchill, Nathan | Leggieri, Melissa | Vuong, Veronica | Tau, Michael | Fornazzari, Luis R. | Thaut, Michael H. | Schweizer, Tom A.

Article Type: Research Article

Abstract: Background: Repeated exposure to long-known music has been shown to have a beneficial effect on cognitive performance in patients with AD. However, the brain mechanisms underlying improvement in cognitive performance are not yet clear. Objective: In this pilot study we propose to examine the effect of repeated long-known music exposure on imaging indices and corresponding changes in cognitive function in patients with early-stage cognitive decline. Methods: Participants with early-stage cognitive decline were assigned to three weeks of daily long-known music listening, lasting one hour in duration. A cognitive battery was administered, and brain activity was measured …before and after intervention. Paired-measures tests evaluated the longitudinal changes in brain structure, function, and cognition associated with the intervention. Results: Fourteen participants completed the music-based intervention, including 6 musicians and 8 non-musicians. Post-baseline there was a reduction in brain activity in key nodes of a music-related network, including the bilateral basal ganglia and right inferior frontal gyrus, and declines in fronto-temporal functional connectivity and radial diffusivity of dorsal white matter. Musician status also significantly modified longitudinal changes in functional and structural brain measures. There was also a significant improvement in the memory subdomain of the Montreal Cognitive Assessment. Conclusion: These preliminary results suggest that neuroplastic mechanisms may mediate improvements in cognitive functioning associated with exposure to long-known music listening and that these mechanisms may be different in musicians compared to non-musicians. Show more

Keywords: Alzheimer’s disease, cognitive reserve, functional MRI, imaging, MRI, music

DOI: 10.3233/JAD-210610

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 819-833, 2021

Authors: Hao, Jing | Qiao, Yuchen | Li, Tingting | Yang, Jianwei | Song, Yang | Jia, Longfei | Jia, Jianping

Article Type: Research Article

Abstract: Background: Serum levels of inflammatory factors, such as C3, C4, C-reactive protein (CRP), immunoglobulin (Ig) G, IgA, and IgM, in patients with Alzheimer’s disease (AD) and their correlation with cognitive function remain unexplored. Objective: To investigate the expression of serum inflammatory factors in patients with AD and its correlation with cognitive function. Methods: Serum levels of C3, C4, CRP, IgG, IgA, and IgM in 200 patients with AD (mild, moderate, and severe) and those in 174 normal controls were assessed. Spearman’s rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and …activities of daily living (ADL). Results: Among these inflammatory factors, C3 and CRP levels were significantly lower, and IgG and IgA levels were significantly higher in the AD group than in the control group (p  < 0.05). There were no significant differences in C4 and IgM levels between the two groups (p  > 0.05). In all participants, CRP level was positively correlated with the Mini-Mental State Examination and Montreal Cognitive Assessment scores (p  < 0.05). In the AD group, IgA level was negatively associated with ADL scores (p  < 0.05). No significant correlation was detected between the other factors and different cognitive scores (p  > 0.05). Conclusion: Inflammatory factors C3, CRP, IgG, and IgA have the potential to serve as biomarkers for AD. Furthermore, serum IgA was not only correlated with AD but also with ADL. These results support the hypothesis that inflammation is involved in the occurrence and development of AD. Show more

Keywords: Alzheimer’s disease, cognitive function, inflammatory factors, serum

DOI: 10.3233/JAD-210552

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 835-842, 2021

Authors: Russin, Kate J. | Nair, K. Sreekumaran | Montine, Thomas J. | Baker, Laura D. | Craft, Suzanne

Article Type: Research Article

Abstract: Background: Exploration of cerebrospinal fluid (CSF) amino acids and the impact of dietary intake on central levels may provide a comprehensive understanding of the metabolic component of Alzheimer’s disease. Objective: The objective of this exploratory study was to investigate the effects of two diets with varied nutrient compositions on change in CSF amino acids levels in adults with mild cognitive impairment (MCI) and normal cognition (NC). Secondary objectives were to assess the correlations between the change in CSF amino acids and change in Alzheimer’s disease biomarkers. Methods: In a randomized, parallel, controlled feeding trial, adults (NC, …n  = 20; MCI, n  = 29) consumed a high saturated fat (SFA)/glycemic index (GI) diet [HIGH] or a low SFA/GI diet [LOW] for 4 weeks. Lumbar punctures were performed at baseline and 4 weeks. Results: CSF valine increased and arginine decreased after the HIGH compared to the LOW diet in MCI (ps = 0.03 and 0.04). This pattern was more prominent in MCI versus NC (diet by diagnosis interaction ps = 0.05 and 0.09), as was an increase in isoleucine after the HIGH diet (p  = 0.05). Changes in CSF amino acids were correlated with changes in Alzheimer’s disease CSF biomarkers Aβ42 , total tau, and p-Tau 181, with distinct patterns in the relationships by diet intervention and cognitive status. Conclusion: Dietary intake affects CSF amino acid levels and the response to diet is differentially affected by cognitive status. Show more

Keywords: Alzheimer’s disease, amino acids, cerebrospinal fluid, diet intervention, mild cognitive impairment

DOI: 10.3233/JAD-210471

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 843-853, 2021