Journal of Alzheimer's Disease - Volume 77, issue 1

Authors: Clare, Linda | Martyr, Anthony | Morris, Robin G. | Tippett, Lynette J.

Article Type: Research Article

Abstract: Background: The onset and progression of dementia can result in changes in the subjective experience of self, impacting on psychological health. Objective: We aimed to explore the extent to which people with mild-to-moderate dementia experience discontinuity in the subjective experience of self, and the factors associated with this experience for people with dementia and their family caregivers. Methods: We used data from the baseline assessment of the IDEAL cohort. Discontinuity in the subjective experience of self was assessed by asking participants about their agreement with the statement ‘I feel I am the same person that I …have always been’. Participants were divided into those who did and did not experience discontinuity, and the two groups were compared in terms of demographic and disease-related characteristics, psychological well-being, measures of ‘living well’, and caregiver stress. Results: Responses to the continuity question were available for 1,465 participants with dementia, of whom 312 (21%) reported experiencing discontinuity. The discontinuity group experienced significantly poorer psychological well-being and had significantly lower scores on measures of ‘living well’. There was no clear association with demographic or disease-related characteristics, but some indication of increased caregiver stress. Conclusion: A significant proportion of people with mild-to-moderate dementia describe experiencing discontinuity in the subjective sense of self, and this is associated with poorer psychological health and reduced ability to ‘live well’ with the condition. Sensitively asking individuals with dementia about the subjective experience of self may offer a simple means of identifying individuals who are at increased risk of poor well-being. Show more

Keywords: Epistemological self, identity, ontological self, quality of life, satisfaction with life, self-persistence

DOI: 10.3233/JAD-200407

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 127-138, 2020

Authors: Xiao, Jinzhong | Katsumata, Noriko | Bernier, Francois | Ohno, Kazuya | Yamauchi, Yuki | Odamaki, Toshitaka | Yoshikawa, Kenji | Ito, Kumie | Kaneko, Toshiyuki

Article Type: Research Article

Abstract: Background: Probiotics use has been associated with modulation of inflammation and considered as a possible intervention for CNS diseases such as mild cognitive impairment (MCI) and dementia. Objective: We aimed to test the effect of the probiotic strain, Bifidobacterium breve A1 (MCC1274), to restore cognition in a physically healthy, suspected MCI population. Methods: In this randomized, double-blind, placebo-controlled trial, 80 healthy older adults suffering from MCI were divided into two even groups to receive once daily either probiotic (B. breve A1, 2×1010 CFU) or placebo for 16 weeks using a computer-generated algorithm. Cognitive …functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Japanese version of the MCI Screen (JMCIS) tests before and after the study as primary and secondary endpoints, respectively. Results: 79 participants completed the study, and no adverse events were observed. RBANS total score was significantly improved in probiotic group compared with placebo (mean between-group difference 11.3 [95% CI 6.7 to 15.8]; p  < 0.0001) after 16 weeks of consumption, in particular with significant improvement in domain scores of immediate memory, visuospatial/constructional, and delayed memory (p  < 0.0001), in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. JMCIS score was also improved versus placebo in ITT analysis (p  = 0.052) and PP analysis (p  = 0.036). Conclusion: Study results indicate B. breve A1 is a safe and effective approach for improving memory functions of suspected MCI subjects. Show more

Keywords: Bifidobacterium, clinical trial, dementia, memory, mild cognitive impairment, probiotics

DOI: 10.3233/JAD-200488

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 139-147, 2020

Authors: Weidling, Ian W. | Wilkins, Heather M. | Koppel, Scott J. | Hutfles, Lewis | Wang, Xiaowan | Kalani, Anuradha | Menta, Blaise W. | Ryan, Benjamin | Perez-Ortiz, Judit | Gamblin, T. Chris | Swerdlow, Russell H.

Article Type: Research Article

Abstract: Background: Mitochondrial dysfunction and tau aggregation occur in Alzheimer’s disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau. Objective: To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations. Methods: Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ 0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects. Results: We found cytochrome oxidase activity was particularly sensitive to acute mtDNA depletion, evidence of metabolic re-programming in the …ρ 0 cells, and a relatively reduced mtDNA content in cybrids generated through AD subject mitochondrial transfer. In each case tau oligomer levels increased, and acutely depleted and AD cybrid cells also showed a monomer to oligomer shift. Conclusion: We conclude a cell’s mtDNA affects tau oligomerization. Overlapping tau changes across three mtDNA-manipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its AD-relevance. Show more

Keywords: Alzheimer’s disease, mitochondria, mitochondrial DNA, oligomers, tau

DOI: 10.3233/JAD-200286

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 149-163, 2020

Authors: Kurasz, Andrea M. | Smith, Glenn E. | McFarland, Maria G. | Armstrong, Melissa J.

Article Type: Research Article

Abstract: Background: Increasing research focuses on ethnic differences in Alzheimer’s disease, but such efforts in other neurodegenerative dementias are lacking. Currently, data on the ethnic profile of cognitively impaired persons with Lewy body disease (LBD) is limited, despite Lewy body dementia being the second most common neurodegenerative dementia. Objective: The study aimed to investigate presenting characteristics among ethnoracially diverse individuals with cognitive impairment secondary to LBD using the National Alzheimer’s Coordinating Center database. Methods: Participants self-identified as African American, Hispanic, or White. We used Kruskal-Wallis and Pearson χ 2 analyses to investigate group differences in presenting …characteristics and linear regression to compare neuropsychological test performance. Results: Presentation age was similar between groups (median 74–75 years). Compared to Whites (n  = 1782), African Americans (n  = 130) and Hispanics (n  = 122) were more likely to be female and single, have less educational attainment, report more cardiovascular risk factors, describe less medication use, and perform worse on select cognitive tests. Hispanics reported more depressive symptoms. Conclusion: Cohorts differences highlight the need for population-based LBD studies with racial-ethnic diversity. Culturally-sensitive neuropsychological tests are needed to determine whether observed differences relate to cultural, social, testing, or disease-related factors. More research is needed regarding how social and biological factors impact LBD care among diverse populations. Show more

Keywords: Alzheimer’s disease centers, dementia, demography, ethnic groups, Lewy body disease, mild cognitive impairment

DOI: 10.3233/JAD-200395

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 165-174, 2020

Authors: Vidoni, Eric D. | Kamat, Ashwini | Gahan, William P. | Ourso, Victoria | Woodard, Kaylee | Kerwin, Diana R. | Binder, Ellen F. | Burns, Jeffrey M. | Cullum, Munro | Hynan, Linda S. | Vongpatanasin, Wanpen | Zhu, David C. | Zhang, Rong | Keller, Jeffrey N.

Article Type: Research Article

Abstract: Background: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors. Objective: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer’s disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk. Methods: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk. Medications were identified in a structured interview process with an onsite pharmacist or qualified designee. Polypharmacy was defined …as use of five or more medications on a regular basis. Descriptive analyses were conducted on the sample as well as direct comparisons of subgroups of individuals with hypertension, diabetes, and hyperlipidemia. Results: The 514 rrAD participants, mean age 68.8 (standard deviation [sd] 6), reported taking different combinations of 472 unique medications at their baseline visit. The median number of medications taken by participants was eight [Range 0–21], with 79.2% exhibiting polypharmacy (n  = 407). Sites differed in their prevalence of polypharmacy, χ 2 (3) = 56.0, p  < 0.001. A nearly identical percentage of the 2,077 prescribed (51.8%) and over the counter (48.2%) medications were present in the overall medication profile. The presence of diabetes (87.5%), hyperlipidemia (88.2%), or both (97.7%) was associated with a higher prevalence of polypharmacy than participants who exhibited hypertension in the absence of either of these conditions (63.2%), χ 2 (3) = 35.8, p  < 0.001. Conclusion: Participants in a dementia risk study had high levels of polypharmacy, with the co-existence of diabetes or hyperlipidemia associated with a greater prevalence of polypharmacy as compared to having hypertension alone. Show more

Keywords: Alzheimer’s disease, dementia, hypertension, inappropriate medication, polypharmacy, risk factor

DOI: 10.3233/JAD-200122

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 175-182, 2020

Authors: Neerland, Bjørn Erik | Halaas, Nathalie Bodd | Idland, Ane Victoria | Henjum, Kristi | Blennow, Kaj | Zetterberg, Henrik | Watne, Leiv Otto

Article Type: Research Article

Abstract: Background: Delirium is associated with dementia and thus biomarkers reflecting neurodegeneration are of interest. Fatty acid-binding protein 3 (FABP3) is a cytoplasmic neuronal protein that has been isolated from the brain. It is released following brain injury and concentrations in cerebrospinal fluid (CSF) are also higher in neurodegenerative disorders such as Alzheimer’s disease (AD). Objective: To examine the relationship between CSF FABP3 concentration and delirium in hip fracture patients compared to a group of cognitively normal controls. Methods: CFS FABP3 concentration was measured in 128 hip fracture patients with (n  = 71) and without (n  = 57) delirium, …and in cognitively unimpaired adults ≥64 years (n  = 124) undergoing elective surgery. Results: CSF FABP3 (pg/ml) concentration (median (IQR)) was higher in hip-fracture patients compared to cognitively normal controls (5.7 (4.2–7.7) versus 4.5 (3.4–6.1), p  < 0.001). There was a significant weak correlation between age and CSF FABP3 (ρ = 0.3, p  < 0.001). After adjustment for age, the association between CSF FABP3 and hip-fracture was no longer statistically significant (β= 0.05, p  = 0.5). There were no significant differences in CSF FABP3 concentration between hip fracture patients with (5.4 (4.1–8.2)) and without (5.8 (4.2–7.2)) delirium. CSF FABP3 concentration correlated positively with CSF AD biomarkers p-tau (ρ = 0.7, p  < 0.01) and t-tau (ρ = 0.7, p  < 0.01). Conclusion: CSF FABP3 concentrations were higher in hip fracture patients compared with cognitively normal older adults, indicating ongoing age-related neurodegeneration in these patients. There were no differences of CSF FABP3 concentrations across delirium groups, suggesting that neuronal damage or degeneration reflected by FABP3 may not be directly linked to delirium pathophysiology. Show more

Keywords: Alzheimer’s disease, Cerebrospinal fluid biomarkers, CSF FABP3, delirium, dementia, hip-fracture

DOI: 10.3233/JAD-200364

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 183-190, 2020

Authors: Tomoto, Tsubasa | Tarumi, Takashi | Chen, Jason | Pasha, Evan P. | Cullum, C. Munro | Zhang, Rong

Article Type: Research Article

Abstract: Background: Cerebral blood flow (CBF) is sensitive to changes in arterial CO2 , referred to as cerebral vasomotor reactivity (CVMR). Whether CVMR is altered in patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer disease (AD), is unclear. Objective: To determine whether CVMR is altered in aMCI and is associated with cognitive performance. Methods: Fifty-three aMCI patients aged 55 to 80 and 22 cognitively normal subjects (CN) of similar age, sex, and education underwent measurements of CBF velocity (CBFV) with transcranial Doppler and end-tidal CO2 (EtCO2 ) with capnography during hypocapnia (hyperventilation) …and hypercapnia (rebreathing). Arterial pressure (BP) was measured to calculate cerebrovascular conductance (CVCi) to normalize the effect of changes in BP on CVMR assessment. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and neuropsychological tests focused on memory (Logical Memory, California Verbal Learning Test) and executive function (Delis-Kaplan Executive Function Scale; DKEFS). Results: At rest, CBFV and MMSE did not differ between groups. CVMR was reduced by 13% in CBFV% and 21% in CVCi% during hypocapnia and increased by 22% in CBFV% and 20% in CVCi% during hypercapnia in aMCI when compared to CN (all p  < 0.05). Logical Memory recall scores were positively correlated with hypocapnia (r  = 0.283, r  = 0.322, p  < 0.05) and negatively correlated with hypercapnic CVMR measured in CVCi% (r  = –0.347, r  = –0.446, p  < 0.01). Similar correlations were observed in D-KEFS Trail Making scores. Conclusion: Altered CVMR in aMCI and its associations with cognitive performance suggests the presence of cerebrovascular dysfunction in older adults who have high risks for AD. Show more

Keywords: Cerebral blood flow, cerebral vasomotor reactivity, hypercapnia, hypocapnia, mild cognitive impairment, transcranial Doppler

DOI: 10.3233/JAD-200194

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 191-202, 2020

Authors: Lombardi, Gemma | Pupi, Alberto | Bessi, Valentina | Polito, Cristina | Padiglioni, Sonia | Ferrari, Camilla | Lucidi, Giulia | Berti, Valentina | De Cristofaro, Maria Teresa | Piaceri, Irene | Bagnoli, Silvia | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Research Article

Abstract: Background: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. Objectives: 1) To verify that cerebrospinal fluid (CSF) Aβ42 /Aβ40 ratio (AβR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aβ42 ; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AβR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. Method: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein …E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. Results: CSF AβR better agreed with Amy-PET compared to CSF Aβ42 (Cohen’s K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AβR values and negative Amy-PET (CSF AβR+/AmyPET–). FDG-PET and all CSF markers (Aβ42 , AβR, p-Tau, t-Tau) were suggestive of Alzheimer’s disease (AD) in 5 of these 6 cases. Conclusion: 1) CSF AβR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAβR+/Amy-PET–discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AβR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD. Show more

Keywords: Aging, Alzheimer’s disease, amyloid, biomarkers, cerebrospinal fluid, diagnosis, PET scan

DOI: 10.3233/JAD-200119

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 203-217, 2020

Authors: Garrido, Sandra | Dunne, Laura | Stevens, Catherine J. | Chang, Esther

Article Type: Research Article

Abstract: Background: Music programs have the potential to provide an effective non-pharmacological tool for caregivers to reduce depression and agitation and increase quality of life in people with dementia. However, where such programs are not facilitated by a trained music therapist, caregivers need greater access to information about how to use music most effectively in response to key challenges to care, and how to pre-empt and manage adverse responses. Objective: This study reports on the trial of a Guide for use of music with 45 people with dementia and their caregivers in residential care facilities and home-based care. …Methods: The study used a pre-post experimental design in which participants were randomly allocated to a treatment group or a waitlist control group. Results: Improvements to quality of life were found in the experimental group over the 6-week period. Significant increases in Interest, Responsiveness, Initiation, Involvement, and Enjoyment were reported for individual listening sessions. Conclusion: The Guide can provide an effective protocol for caregivers to follow in selecting music to manage particular challenges to care, confirming the need for caregivers to be prepared to monitor and manage potential negative responses. Show more

Keywords: Aged care, agitation, Alzheimer’s disease, arts-based therapies, geriatric depression, health guidelines

DOI: 10.3233/JAD-200457

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 219-226, 2020

Authors: Cavalcante, Bruno Remígio | de Souza, Mariana Ferreira | Falck, Ryan Stanley | Liu-Ambrose, Teresa | Behm, David G. | Pitangui, Ana Carolina Rodarti | de Araújo, Rodrigo Cappato

Article Type: Research Article

Abstract: Background: Activities which simultaneously challenge both physical and cognitive function are promising strategies for promoting cognitive function. Objective: To examine the effects of resistance exercise with instability and traditional resistance exercise compared with a health education control on cognitive function in older adults with cognitive complaints. Methods: Sixty-seven participants were randomized to either 12 weeks of thrice-weekly resistance exercise (RE = 23), RE with instability (REI = 22), or a weekly health education control (CON = 22). At each training session, RE and REI participants performed seven exercises for three sets and 10–15 repetitions. REI participants performed each exercise using instability devices. …The primary outcome was a composite score of global cognitive function. Secondary outcomes included composite scores for cognitive sub-domains and physical function. Results: Most participants were women (REI: 77%; RE = 78%; CON = 77%; mean age of 71 years), and did not need transport to the intervention site. At completion, compared with CON, REI and RE did not significantly improve on global cognition or each cognitive sub-domain. Both exercise groups improved on the timed up and go (REI - CON: –1.6 s, 95% CI: [–2.6, –0.5]; RE - CON: –1.4 s, 95% CI: [–2.4, –0.5) and 1-RM (REI - CON: 24 kg, 95% CI: [11, 36]; RE - CON: 25 kg, 95% CI: [12, 37]). An exploratory contrast showed that compared with RE, REI promote greater gains on global cognition (2.20, 95% CI: [0.10, 4.31]) and memory (1.34; 95% CI: [0.15, 2.54]). Conclusion: REI did not substantially improve cognitive function but did promote physical function among older adults with cognitive complaints. However, compared with RE, REI improved global cognition and memory. Show more

Keywords: Aging, cognitive impairment, exercise, physical performance, randomized controlled trial, resistance training

DOI: 10.3233/JAD-200349

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 227-239, 2020