bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic medications and dementia risk: an umbrella review
Authors: Mukadam Naaheed , Belessiotis Clara , Yap Ying Feng , Talwar Shivangi , Bruun Andrea , Li Wenqianglong , Ward Harry , Letrondo Pilar , Morelli‐Batters Madeleine , Lin Rongyu , Eskinazi Michelle , Wright Talen , Hayes Joseph 
Published: January 2025

AbstractBackgroundDementia is a growing global public health challenge. Previous meta‐analyses have found that systemic medications may modulate dementia risk. We aimed to provide an overview of this evidence.MethodWe conducted an umbrella review of meta‐analyses (PROSPERO CRD42021226307). MEDLINE, AMED, PsycINFO, and Embase were searched from inception to 25th January 2023. Only peer‐reviewed meta‐analyses examining dementia risk and systemic medications in humans were included, with no restrictions on language. Studies examining cognitive decline were excluded. Participant details, study types, diagnostic criteria, publication bias, heterogeneity, and summary effect estimates were extracted from publications. Study quality was assessed using the AMSTAR‐2. Data extraction and quality ratings were carried out independently by two authors.Result60 studies were included in the final review. Included meta‐analyses examined anti‐hypertensives (n = 17), statins (n = 7), antacids (n = 7), non‐steroidal anti‐inflammatory drugs (NSAIDs) (n = 6), diabetes medications (n = 4), hormone replacement therapy (n = 4), androgen deprivation therapy (ADT) (n = 4), psychotropic medications (n = 4), anticholinergics (n = 3), anticoagulants (n = 2), and vitamin E (n = 2). Number of participants in each review ranged from 842 to 9,162,509. Mean age ranged from 59 to 78 years, and between 0 and 100% of participants were female. There was a trend towards decreased risk of dementia with antihypertensives, statins, NSAIDs, anticoagulants, and vitamin E, and towards increased risk with ADT, benzodiazepines, and anticholinergic medications.ConclusionAvailable data were primarily observational, leading to biases such as confounding by indication, and few studies met a high number of critical quality criteria. Randomised‐controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence and a possible association between hormone replacement therapy and increased risk of dementia. Our review provides an overview of what kinds of medication are associated with dementia risk, to guide clinical practice and future research. Currently there are no systemic medications that should be prescribed with the primary aim of reducing dementia risk.
Sleep Patterns in Midlife and Brain Age
Authors: Cavaillès Clémence , Dintica Christina S. , Habes Mohamad , Leng Yue , Carnethon Mercedes , Yaffe Kristine 
Published: January 2025

AbstractBackgroundPrevious studies have linked sleep disturbances with an increased risk of dementia among older adults. However, the association between sleep patterns and brain health earlier in life is less understood. We aimed to determine how sleep in early midlife relates to an MRI‐derived indicator of brain age in late midlife.MethodWe analyzed 619 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. At the study baseline (2000‐2001), participants answered six binary questions about their typical sleep patterns, including general sleep quality, sleep duration, daytime sleepiness, trouble falling asleep, waking up at night, and early awakening. We quantified the number of poor sleep characteristics (range from 0 to 6) and categorized them into three groups (0‐1; 2‐3; >3). On average 15 years later (2015‐2016), brain MRIs were obtained, and a high dimensional pattern analysis was used to determine brain age by quantifying individual differences in age‐related atrophy. We used multivariable linear regressions to examine the association between sleep patterns and brain age.ResultAt baseline, the participants’ mean age was 40.4 (±3.4) years, 52% were women, and 38% were Black. Around 70% of participants reported 0‐1, 22% reported 2‐3, and 8% reported >3 poor sleep characteristics. After adjusting for demographics, lifestyle factors, and comorbidities, participants reporting 2‐3 and >3 poor sleep characteristics had 1.9‐year (95% confidence interval (CI) = 0.54;3.16) and 3.1‐year (95%CI = 1.14;5.11) greater brain age, respectively, compared with participants reporting 0‐1 poor sleep characteristic. Of the individual questions, sleep quality, trouble falling asleep, early awakening, and waking up at night were associated with a 1.7 (95%CI = 0.25;3.16), 1.6 (95%CI = 0.06;3.08), 2.1 (95%CI = 0.71;3.50), and 1.2 (95%CI = 0.08;2.23) years older brain age, respectively.ConclusionThese findings suggest an association of poor sleep in early midlife with advanced brain age 15 years later. Further research is needed to clarify the underlying mechanisms linking sleep to brain aging earlier in life.
EEG utilization to assess the efficacy of Person‐Centered Communication Intervention
Authors: Kim Dongseon 
Published: January 2025

AbstractThis study employs electroencephalography (EEG) to assess the efficacy of a person‐centered communication intervention in the context of dementia care. Seventy‐seven individuals in the early stage of dementia, attending day care centers, were divided into experimental and control groups following a non‐equivalence control design. The communication intervention consisted of 30 minutes of semi‐structured, topic‐specific in‐person interactions, incorporating elements of self‐introduction, rapport‐building, emotional exploration, reminiscence, and cognitive stimulation. To enhance communication with peopel with dementia, techniques such as acknowledgment, validation and other communication skills were employed, aligning with the principles of person‐centered care. Data comprises of EEG measurements on the points of prefrontal lobe before and after the intervention, and assessment of emotional changes and agitated behaviors using the Observed Emotion Rate Scale (OERS) and Agitational Behavior Scale (ABS).Results indicate a noteworthy reduction in theta waves which are known to be associated with emotional states, alongside significant alterations in alpha and beta waves, indicative of attention increase. Moreover, statistically significant emotional changes were observed, including increased happiness and attention, as well as decreased anger, anxiety, and agitation. Notably, behavioral symptoms were found to be correlated with emotional states of anxiety and agitation, both of which exhibited reductions post‐intervention. In conclusion, the person‐centered communication intervention yielded changes in brain wave patterns and improvements in emotional and behavioral states. This study contributes to the field by providing quantitative evidence of the efficacy of person‐centered communication in alleviating anxiety and behavioral symptoms among people with dementia.
Kimel Family Centre for Brain Health and Wellness: Protocol for a Naturalistic Longitudinal Personalized Multidomain Preference Dementia Risk Reduction Trial
Authors: Anderson Nicole D. , D'Amico Danielle , Rotenberg Shlomit , Gillen Jenna , Moore Daniel , Tan Brian , Binns Malcolm , Santarossa Melanie , Chertkow Howard ,   The Canadian Consortium on Neurodegeneration in Aging (CCNA), CAN‐THUMBS UP
Published: January 2025

AbstractBackgroundThe Kimel Family Centre for Brain Health and Wellness is a research‐driven community centre testing the efficacy of a naturalistic longitudinal personalized multidomain preference dementia risk reduction intervention on dementia risk and cognition. The objective of this protocol is to validate this approach by following people for two years.MethodParticipants (n = 325) will be 50 years of age or older, without a diagnosis of dementia, and sufficiently fluent in English to complete the assessments and understand program instructors. Participants will receive a comprehensive dementia risk assessment, including both nonmodifiable and modifiable risk factors, from which they will receive a Personalized Dementia Risk Report and Program Strategy, indicating health conditions increasing dementia risk, and their risk level in five risk domains: physical activity, brain‐healthy eating, cognitive engagement, social connections, and mental wellbeing. Participants will select programs to meet their Personalized Program Strategy. We will examine the effects of this program on cognition (MoCA and Cogniciti’s Brain Health Assessment) and risk in the five domains, as a function of adherence (attendance), compared to those of 300 individuals who will complete the Canadian Consortium on Neurodegeneration’s CAN‐THUMBS Up online, educational program on modifiable dementia risk factors, called Brain Health PRO.ResultWe expect better maintenance of cognition and reduction in the five dementia risk domains in Kimel Family Center participants, compared to Brain Health PRO participants.ConclusionThere is an urgent need to develop scalable multidomain programs for dementia prevention. This innovative approach overcomes a number of limitations present in prior multidomain dementia prevention trials. Once validated, the approach will be scaled to other community centres, to benefit a greater number of geographically dispersed individuals.
Significance of Donanemab Versus Placebo in Alzheimer’s Disease Pathogenesis. A Systematic Review
Authors: Ortíz Arid Barragán , Flores Marcos Arreola , Ortega Christan J Monge , Lara Sofia Andrade , Castillo David A Chávez , Rodríguez Sergio M Carrillo , Ortega Thania F Estrada , Posadas Maria F Estrada , Suárez Gilberto Mauricio 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is a neurodegenerative disease, characterized by a decrease in cognitive and behavioral functions of patients. Between the multiple potential disease‐modifying therapeutics for AD, we have monoclonal antibodies as aducanumab, lecanemab, and donanemab. Recent results from the TRAILBLAZER‐ALZ trial, highlighted donanemab as a promising monoantibodies treatment of early symptomatic AD. Donanemab targets the N‐terminal region of pyroglutamate Aβ plaques. It is designed to bind selectively to these plaques. This targeting mechanism offers a focused approach in the treatment and potential amelioration of the disease’s symptoms.Methodsystematic search in the meta search engines of Pubmed and TRIP database, described in the diagramResultDonanemab follows a two‐compartment model with first order elimination and in several studies found that reduction of amyloid plaque is associated with maintenance of donanemab threshold serum concentrations above 4.43 µg/ml. The difference in iADRS score changed ‐6.86 in donanemab group and ‐10.06 in placebo group. Also amyloid plaques clearance measured by florbetapir PET was 85.06 centiloids more than in the placebo group, −84.13 centiloids for donanemab vs. 0.93 centiloids for placebo. In early stages of Alzheimer’s disease, donanemab as treatmenet, resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks. Among the side effects that were seen across studies were amyloid‐related edema or stroke (mostly asymptomatic) occurring with donanemab and no exposure threshold was identified as being associated with an increased risk of ARIA‐E. The apparent effect of donanemab on ARIA‐E was generated primarily in participants who were carriers of the APOE ε4 gene.ConclusionPreliminary data indicates its potential in effectively impeding the progression of the disease, as observed in the extracted articles. In order to comprehensively grasp the implications of the observed rise in CSF Aβ42 and its correlation with cognitive and clinical effects. While there is limited research available, the current evidence suggests that donanemab is indeed efficacious in halting the advancement of the disease. Donanemab has emerged as a promising option, yet its status is not definitive due to the associated risk of developing ARIA‐E during its administration.
Fatigue predicts 10‐year risk of incident dementia in a population representative cohort of United States Medicare beneficiaries
Authors: Moored Kyle D. , Glynn Nancy W. , Carlson Michelle C , Donahue Patrick T. , Schrack Jennifer A 
Published: January 2025

AbstractBackgroundFatigue is prevalent in later life and may increase dementia risk independent of health conditions. Yet, existing epidemiologic studies include samples that are not nationally representative of U.S. older adults. These studies have also not examined fatigue in combination with current physical activity level, which is important because higher fatigue ratings may also stem from a more active lifestyle that could lower dementia risk. We examined whether self‐reported fatigue, both independently and jointly with self‐reported physical activity, was associated with 10‐year risk of incident dementia in U.S. older adults.MethodParticipants were from the National Health and Aging Trends Study (2011‐2021, N = 5,167), a population representative cohort of U.S. Medicare beneficiaries. Fatigue was self‐reported as having low energy in the past month that interfered with activities (yes/no). Participants also reported past‐month engagement in any vigorous activity that increased their heart rate (e.g., working out; yes/no). Probable dementia cases were ascertained using cognitive testing and proxy reporting. Analyses included discrete‐time proportional hazards models with sample weighting to account for survey design and adjusted for baseline age, sex, race/ethnicity, education, BMI, number of health conditions, smoking status, social isolation, and depressive symptoms.ResultTwenty‐nine percent of participants reported fatigue. Frequencies of combined fatigue and activity groups included: “active/no fatigue” (31%), “active/fatigued” (8%), “inactive/no fatigue” (40%), “inactive/fatigued” (21%). There were 1,089 incident cases of probable dementia for up to 10 years of follow‐up (M±SD = 5.4±3.6 years). Individuals reporting fatigue (vs. no fatigue) had a 16% greater risk of incident dementia after full covariate adjustment (HR = 1.16, 95% CI: 1.01, 1.34, p = .041). Compared to the “active/no fatigue” group, the “inactive/fatigued” group had a 40% greater risk of incident dementia after adjustment (HR = 1.40, 95% CI: 1.16, 1.69, p = .001), but risk did not significantly differ for “active/fatigued” and “inactive/no fatigue” groups (p’s>.05).ConclusionFatigue may be a signal of increased risk of incident dementia in U.S. older adults, independent of depressive symptoms and other health characteristics. Individuals reporting both fatigue and inactivity had the highest risk of dementia, suggesting that fatigue may be a symptom of underlying pathological processes, especially among those with low activity levels.
Gender differences in the impact of illiteracy on dementia risk among community‐dwelling older adults
Authors: Oh Dae Jong , Han Ji Won , Kim Tae Hui , Kwak Kyung Phil , Kim Bong Jo , Kim Shin Gyeom , Kim Jeong Lan , Moon Seok Woo , Park Joon Hyuk , Ryu Seung‐Ho , Youn Jong Chul , Lee Dong Young , Lee Dong Woo , Lee Seok Bum , Lee Jung Jae , Jhoo Jin Hyeong , Kim Ki Woong 
Published: January 2025

AbstractBackgroundIlliteracy is highly prevalent in older women than in men, but whether the impact of illiteracy on dementia risk is differed by gender remains unclear.MethodWe enrolled 5,217 non‐demented older adults aged ≥ 60 years from the Korean Longitudinal Study on Cognitive Aging and Dementia. Presence of illiteracy was assessed by research nurses and the diagnoses of incident dementia and Alzheimer’s disease (AD) were made by standardized diagnostic interview by geriatric psychiatrists. Neuropsychologists assessed the cognitive performance by using Korean version of Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet Neuropsychological Assessment Battery. Multivariate Cox proportional hazard regression and linear mixed model analyses were used to identify the impact of illiteracy on the risks of all‐cause dementia/AD and cognitive decline during the 8‐year follow‐up respectively.ResultTotally, 283 (98 men [4.4%]; 185 women [6.2%]) cases of all‐cause dementia and 227 (71 men [3.2%]; 156 women [5.2%]) cases of AD were identified during the follow‐up period (5.8 ± 2.4 years). Among 901 illiterate participants, 9 (7.9%) men and 101 (12.8%) women developed all‐cause dementia whereas 5 (4.4%) men and 89 (11.3%) women developed AD. Illiteracy was found to pose 2.8‐fold (Hazard Ratio [HR] = 2.79, 95% Confidence Interval [CI] = 1.95 – 3.99) and 2.9‐fold (HR = 2.89, 95% CI = 1.97 – 4.25) increased risks of all‐cause dementia and AD respectively in women. The HRs for association of illiteracy with all‐cause dementia (HR = 2.48, 95% CI = 1.66 – 3.68) and AD (HR = 2.54, 95% CI = 1.66 – 3.90) risks remained significant even when we separately analyzed the less educated women (educational years ≤ 6 years, n = 1,830). However, there was no significant association in men. The impact of illiteracy on the progression of cognitive decline was more pronounced in women (β = ‐0.962, SE = 0.147) than in men (β = ‐0.618, SE = 0.338).ConclusionThe impact of illiteracy on dementia risk may be more significant in women than in men, irrespective of the educational attainment of the study population. Illiterate older women should be considered the primary target population for dementia prevention strategies.
Estimating Potential Eligibility for Disease Modifying Therapies for Alzheimer’s Disease Using Population‐Based Data in Alberta, Canada
Authors: Chowdhury Mohammad Z I , Thomas Gavin , Smith Eric E. , Bronskill Susan E , Kirkham Julia G , Ismail Zahinoor , Goodarzi Zahra , Roach Pamela , Ewa Vivian , Vedel Isabelle , Gruneir Andrea , Seitz Dallas 
Published: January 2025

AbstractBackgroundDisease modifying therapies (DMTs) for Alzheimer’s disease (AD) have been approved in some countries although these treatments will require substantial health resources for their implementation. Initial capacity planning to identify the resources required to support DMTs begins with estimating the number of people with dementia who may be eligible for DMTs. We estimated the potential number of individuals with dementia who are eligible for DMTs using population‐based data in Alberta, Canada.MethodWe used provincial administrative health databases in Alberta, Canada (population ∼4.5 million) to identify all people newly identified with dementia between April 1, 2013 and March 31, 2022 using a validated dementia case ascertainment algorithm. The characteristics of this population were then described at the time of diagnosis including demographics, conditions potentially contributing to the diagnosis of dementia (e.g. stroke, parkinsonism), and medical contraindications to treatment (e.g. cancer, seizures). The characteristics of individuals with dementia were then compared to the inclusion criteria used in AD DMT trials to estimate the proportion of individuals with dementia who may be eligible for DMTs. We then compared the characteristics of individuals who were determined to be eligible for DMTs compared to those who were not eligible.ResultA total of 77,479 individuals were identified with incident dementia during the study period with a mean age of 80.6 years and 58% were female. In this group, 15,044/77,479 (19%) had conditions other than AD as a potential cause of their dementia. Medical contraindications to DMTs were present in 24,580/62,435 (39%) of all individuals who had AD as their probable cause of dementia. Overall, 37,855/77,479 (49%) of the entire dementia population could potentially go on to receive biomarker testing to determine DMT eligibility. Individuals who were younger and women were more likely to be potentially eligible for DMTs at the time of dementia diagnosis.ConclusionApproximately half of all people diagnosed with dementia in Alberta could be eligible for DMTs based on their health history. Additional information on cognitive test scores, neuroimaging, and biomarker results are required to further refine estimates of the number of individuals potentially eligible to receive DMTs in Canada.
Looking to the future: How can clinical trials be designed in partnership with our participants?
Authors: Schott Jonathan M 
Published: January 2025

AbstractThe recent positive phase 3 clinical trials of new treatments and their licensing and roll‐out in the US and other countries represents a major turning point in Alzheimer’s disease research. As has been the case with many other diseases, e.g. multiple sclerosis and stroke, it is hoped that these successes will act as a catalyst, spurring the development not only of the next generation of amyloid immunotherapies but a range of other therapeutic approaches targeting different aspects of Alzheimer pathology, and different forms of dementia. How future trials are designed will likely have major impacts on their chances of success but also how they are deployed when licensed in clinical practice. It is of course vital that trials are designed to prioritise patient safety and use robust methodologies to produce valid results while maximising the possibility of gaining insights into mechanisms and any side‐effects. However, it is also imperative that protocols are acceptable to participants, and designed wherever possible to maximise compliance, improve accessibility, reduce cost and increase representativeness. Factors that need to be considered include those which may be dependent on the drug’s mode of action and likely effect, e.g. the length of the trial, the method of trial drug delivery, and any requirements for safety monitoring. Factors where there may be scope for change include, but are not limited to, the required number of trial visits, the length of assessments (e.g. including shorter MRI protocols for safety monitoring), the possibility of remote or at home as opposed to in‐hospital visits where possible, and simplifying methods for determining molecular pathology both as entry and potentially stopping criteria (e.g. if plasma can be used instead of CSF or molecular imaging). If we are to maximise the reach of our trials, ensure they are truly representative of all the people who might benefit, and increase recruitment rates, it is vital that we engage with study participants in the design of future studies, engage them as advocates for our research, and promote and actively involve individuals from diverse and under‐represented backgrounds.