American Journal of Alzheimers Disease and Other Dementias

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly
Hsieh SW, Hsiao SF, Liaw LJ, Huang LC and Yang YH
Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia.
Lifestyle Medicine Program Improves Memory and Executive Functions of Older Adults With Mild Cognitive Impairment
Cheung MC, Sze SL and Chan AS
The Lifestyle Medicine Program (CLMP) was found to enhance the memory and executive functions of older adults with or without subjective memory complaints. The present study investigated whether similar beneficial effects can be extended to mild cognitive impairment (MCI). Twenty-four older adults with MCI were randomly assigned to receive the CLMP (the experimental group) or strategic memory training (SMT; the active control group) for 10 weeks. They were assessed by neuropsychological tests at baseline and post-intervention. Older adults showed similar visual and verbal memory improvements after receiving the CLMP and SMT. Yet, only those who received the CLMP showed distinct improvements in planning/organization, working memory, and attention in terms of accuracy, with greater cognitive gains associated with older age and lower levels of education and baseline cognitive functions. This study provides preliminary evidence for the effects of the CLMP on improving memory, attention, and executive functions in MCI.
Adapted Home-Based Exercises in Dementia: An Exploratory Pre-post Pilot and Feasibility Study
Carrard S, Eyer S, Hilfiker R and Mittaz Hager AG
The goals of this exploratory pre-post pilot and feasibility study (NCT04916964) were to assess the feasibility and effectiveness of an adapted Test-and-Exercise home-based exercise program on basic functional mobility and executive functions in persons with prodromal or mild Alzheimer's disease. Participants followed an 8 week exercise program at home, once per week with a physiotherapist and twice per week with their usual caregiver or independently. Functional mobility and executive functions were assessed before and after the intervention. Feasibility criteria were recruitment opportunity, participation agreement rate, cost adequacy, and drop-out rate. Twelve participants aged 80.83 ± 4.65 years took part in the study. All the basic functional mobility measures showed small effect sizes. Concerning executive functions, 5 measures showed small to moderate effect sizes. The 4 feasibility criteria were met. A larger scale study would, however, need adaptations and prior research on the ability of this population to use touch-screen technology.
Mediating Factors Associated With Physical Activity in Older Adults at Increased Dementia Risk
Cardona MI, Luppa M, Zülke A, Kroeber ES, Bauer A, Döhring J, Escales C, Brettschneider C, Frese T, Kosilek RP, Gensichen J, Hoffmann W, Kaduszkiewicz H, König HH, Wiese B, Riedel-Heller SG and Thyrian JR
While regular physical-activity (PA) is beneficial, multimorbid individuals at increased dementia risk may exhibit reduced PA levels. Thus, a more comprehensive understanding of mediating factors responsible for inactivity in this population is needed. This study investigated the impact of a multimodal intervention on PA changes at 24-month follow-up and associated mediating factors among community-dwelling patients aged 60-77, with increased dementia risk determined by the CAIDE Dementia Risk Score. Of 1030 participants recruited, 819 completed the assessment. Thus, a generalized estimating equations model initially assessed differences in PA over 24 months, followed by a tree analysis identifying mediating factors influencing PA changes post-intervention. While no significant effect on regular PA was found during the follow-up ( = .674), subgroup analysis revealed improved self-efficacy ( = .000) associated with increased engagement in PA. Incorporating self-efficacy elements into future strategies is crucial for promoting PA among individuals with multimorbidity and at increased dementia risk.
Positive Behaviour Support Training for Staff and Family Members Supporting Residents With Dementia in Aged Care Settings
Fisher AC, Reschke K, Shah N, Cheung S, O'Connor C and Piguet O
This study examined the acceptability and usefulness of Positive Behaviour Support (PBS) training in enhancing the capabilities of support staff and family members providing behaviour support to residents with dementia in residential aged care (RAC).
Determinants of Time to Diagnosis in Young-Onset Dementia
Sharma S, Ilse C, Brickell K, Le Heron C, Woods K, O'Mara Baker A, Tippett L, Curtis MA and Ryan B
Timely diagnosis of young-onset dementia (YOD) is critical. This study aimed to identify factors that increased time to diagnosis at each stage of the diagnostic pathway. Participants were patients diagnosed with YOD (n = 40) and their care partners (n = 39). Information was obtained from questionnaires, and review of medical records. Mean time from symptom onset to YOD diagnosis was 3.6 ± 2 years. Suspicion of depression/anxiety at presentation was associated with significantly increased time from presentation to specialist referral. Neurologist-diagnosed YOD was the fastest route to a diagnosis, whereas diagnoses made by other specialists significantly increased the time from first specialist visit to diagnosis. By investigating multiple stages of the diagnostic pathway, we identified two factors that increased time to diagnosis: suspicion of depression/anxiety at presentation delayed specialist referral from primary care, and diagnosis by a specialist other than a neurologist delayed diagnosis of YOD.
Recruiting Persons With Dementia: A Systematic Review of Facilitators, Barriers, and Strategies
Hirt J, Beer T, Cavalli S, Cereghetti S, Pusterla ERG and Zeller A
Study recruitment of persons with dementia is challenging. We aimed to assess facilitators, barriers, and strategies to identify and approach persons with dementia for recruitment to dementia care studies. We systematically searched MEDLINE/PubMed, CINAHL, Web of Science, and other sources (ORRCA [Online Resource for Research in Clinical triAls]; pertinent evidence syntheses; citation searching) and narratively summarised the results (PROSPERO CRD42022342600). Facilitators and barriers consisted of "characteristics of participants, researchers, clinical contact persons", "study characteristics", and "communication with participants". The highest number of participants were recruited by study information in electronic and print formats, as well as by networking and collaboration. Advertisements proved to be the most expensive way of recruitment. There is limited evidence on the impact of recruitment strategies to identify persons with dementia for recruitment to dementia care studies. Our analysis of facilitators and barriers may inform research teams in designing strategies to identify persons with dementia for recruitment purposes.
Different Splice Isoforms of Peripheral Triggering Receptor Expressed on Myeloid Cells 2 mRNA Expressions are Associated With Cognitive Decline in Mild Dementia Due to Alzheimer's Disease and Reflect Central Neuroinflammation
Chiang YK, Lin YS, Chen CY, Lirng JF, Yang YH, Lee WJ and Fuh JL
Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2 mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2 mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation.
Development and Validation of an Automatic Computerized Neurocognitive Battery in Chinese
Zhang J, Hong ZY, Yang L, Li XJ and Ye F
Neuropsychological test batteries, which accurately and comprehensively assess cognitive functions, are a crucial approach in the early detection of and interventions for cognitive impairments. However, these tests have yet to gain wide clinical application in China owing to their complexity and time-consuming nature. This study aimed to develop the Computerized Neurocognitive Battery for Chinese-Speaking participants (CNBC), an autorun and autoscoring cognitive assessment tool to provide efficient and accurate cognitive evaluations for Chinese-Speaking individuals.
Quality of Life and Relationships in Caregivers of People With Dementia. A Gender Perspective
Bjørge H, Kvaal K and Ulstein I
Home-dwelling people with dementia rely on their family members to be able to stay at home. This affects the family caregivers' quality of life (QoL). However, less is known about how male and female caregivers differ in their QoL. Our study aimed to investigate gender differences in caregivers' quality of life (QoL), whether emotional relationships influence QoL, and how their QoL changes over time. The study applied a cross-sectional and a longitudinal design to examine a total of 208 caregivers, 158 female and 50 male caregivers, and their family member with dementia. Regression analysis and t-tests were performed to identify what characteristics about caregivers and care receivers influence male and female QoL, and whether caregivers' QoL developed after one year. Both male and female caregivers' depression influenced their QoL. For females, their own social distress influenced their QoL, and for males, their experience of their care receivers' overemotional attitude influenced their QoL. From baseline to one-year follow-up their QoL decreased while their distress and experience of care receivers' emotional attitudes was stable. Significant gender-specific differences were found, indicating that gender must be considered when approving caregivers' needs and planning interventions for caregivers.
The Role of Epileptic Activity in Alzheimer's Disease
Chen TS, Lai MC, Hong WP and Huang CW
Alzheimer's disease (AD) is the most common cause of dementia. Epileptic seizures or epileptic activity have been detected in AD, and people with epilepsy have a higher risk of dementia compared to the general population. This suggests that seizures or epileptic activity might often coexist with AD. It is increasingly evident that epileptic activity or seizures are common but often overlooked comorbidities of AD. However, the causal relationship between seizures, epileptic activity and cognitive decline remains uncertain. Experimental data show that amyloid-β (Aβ) and Tau protein can cause neuronal hyperexcitability and has epileptogenic effects. Neural network hyperexcitation regulates the ratio of Aβ isoforms and is linked to the initiation of AD, indicating a shared mechanism. Clinical studies suggest that cognitive impairment accelerates in AD patients with seizures or epileptic activity. This review discusses the relationship between epileptic seizures and AD, the impact of epileptic activity in AD, and potential treatments.
A Study on Machine Learning Models in Detecting Cognitive Impairments in Alzheimer's Patients Using Cerebrospinal Fluid Biomarkers
Tiwari VK, Indic P and Tabassum S
Several research studies have demonstrated the potential use of cerebrospinal fluid biomarkers such as amyloid beta 1-42, T-tau, and P-tau, in early diagnosis of Alzheimer's disease stages. The levels of these biomarkers in conjunction with the dementia rating scores are used to empirically differentiate the dementia patients from normal controls. In this work, we evaluated the performance of standard machine learning classifiers using cerebrospinal fluid biomarker levels as the features to differentiate dementia patients from normal controls. We employed various types of machine learning models, that includes Discriminant, Logistic Regression, Tree, K-Nearest Neighbor, Support Vector Machine, and Naïve Bayes classifiers. The results demonstrate that these models can distinguish cognitively impaired subjects from normal controls with an accuracy ranging from 64% to 69% and an area under the curve of the receiver operating characteristics between 0.64 and 0.73. In addition, we found that the levels of 2 biomarkers, amyloid beta 1-42 and T-tau, provide a modest improvement in accuracy when distinguishing dementia patients from healthy controls.
Heart Rate and its Variability From Short-Term ECG Recordings as Potential Biomarkers for Detecting Mild Cognitive Impairment
Xavier A, Noble S, Joseph J, Ghosh A and Issac TG
Alterations in Heart Rate (HR) and Heart Rate Variability (HRV) reflect autonomic dysfunction associated with neurodegeneration making them biomarkers suitable for detecting Mild Cognitive Impairment (MCI). The study involves 297 urban Indian participants [48.48% (144) were male and 51.51% (153) were female]. MCI was detected in 19.19% (57) of participants and the rest, 80.8% (240) of them were healthy. ECG recordings spanning 10 s were collected and R-peaks were detected. Machine learning algorithms like were employed to further validate the features. The mean of R-to-R (NN) intervals ( = .0021), the RMS of NN intervals ( = .0014), the SDNN ( = .0192) and the RMSSD ( = .0206) values differ significantly between MCI and non-MCI. Machine learning classifiers, SVM, DA, and NB show a high accuracy of 80.801% on RMS feature input. HR and its variability can be considered potential biomarkers for detecting MCI.
Interrelationship of Sleep Disturbances and Cognitive Status on Mortality
Mattos MK, Zawar I, Manning C, Patrie J and Quigg MS
Sleep disturbances may promote the development and advancement of Alzheimer's disease. Our purpose was to determine if sleep disturbances were associated with earlier mortality while accounting for cognition. The National Alzheimer's Coordinating Center database was used to evaluate mortality risk conferred by sleep, and the Montreal Cognitive Assessment score determined cognitive status. Demographics, sleep disturbances, cognitive status, and comorbid/other neuropsychiatric conditions were examined as predictors of survival time via Cox regression. The sample (N = 31,110) had a median age [interquartile range] of 72 [66, 79] years, MoCA score of 23 [16, 26], and survival time of 106.0 months [104.0,108.0]; 10,278 (33%) died during follow-up; 21% (n = 6461) experienced sleep disturbances. Sleep disturbances impacted survival time depending on cognition, with the greatest effect in transition from normal to cognitive impairment ( < .001). Findings support that sleep disturbances negatively impact survival time, and the impact of sleep disturbances on survival time is interrelated with cognition.
Identification of Dementia & Mild Cognitive Impairment in Chinese Elderly Using Machine Learning
Ying TT, Zhuang LY, Xu SH, Zhang SF, Huang LJ, Gao WW, Liu L, Lai QL, Lou Y and Liu XL
To assess the role of Machine Learning (ML) in identification critical factors of dementia and mild cognitive impairment.
The Psychological Symptoms and Their Relationship to the Quality of Life Among Dementia Patients Caregivers
Baniah Lafee Alzaben M and Suhail Mousa Shawaqfeh B
The study aims to identify psychological symptoms (depression and anxiety) and their relationship to the quality of life among dementia patients' caregivers, and whether there are differences in the level of each of them due to the gender variable. The study follows the correlational approach, with a sample of 174 dementia patients' caregivers. To pursue the analysis, the study uses 3 measurement tools: anxiety, depression, and quality of life. The results show that the level of depression, anxiety, and quality of life among dementia patients' caregivers is moderate. It also finds that there is a positive relationship between anxiety and depression, and there is a negative relationship between quality of life and anxiety and depression. There are no differences in the level of depression and anxiety due to gender, as the study finds female caregivers to have a higher level of quality of life.
A Review of the Role of Estrogens in Olfaction, Sleep and Glymphatic Functionality in Relation to Sex Disparity in Alzheimer's Disease
Ekanayake A, Peiris S, Ahmed B, Kanekar S, Grove C, Kalra D, Eslinger P, Yang Q and Karunanayaka P
Several risk factors contribute to the development of Alzheimer's disease (AD), including genetics, metabolic health, cardiovascular history, and diet. It has been observed that women appear to face a higher risk of developing AD. Among the various hypotheses surrounding the gender disparity in AD, one pertains to the potential neuroprotective properties of estrogen. Compared to men, women are believed to be more susceptible to neuropathology due to the significant decline in circulating estrogen levels following menopause. Studies have shown, however, that estrogen replacement therapies in post-menopausal women do not consistently reduce the risk of AD. While menopause and estrogen levels are potential factors in the elevated incidence rates of AD among women, this review highlights the possible roles estrogen has in other pathways that may also contribute to the sex disparity observed in AD such as olfaction, sleep, and glymphatic functionality.
A Longitudinal Dose-Response Curve Between Leisure-Time Physical Activity and the Prevalence of Diabetes Based on the Different Levels of Cognitive Function Among Older Adults
Lee J, Kim J, Ju HJ, An SJ and Woo B
This study investigated a dose-response relationship between Leisure-Time Physical Activity participation (LTPA) and the risk of diabetes and a comparison of the risk across different cognitive function groups among older adults. The Health and Retirement Study data were used from 2012 to 2020 (n = 18 746). This study conducted a Cox Proportional Hazard Regression to investigate the Dose-Response Curve between the prevalence of diabetes and the covariates following a level of LTPA participation. The result presented that the Odds Ratio continuously decreased as the level of LTPA participation increased. Among the three cognitive function groups, the high group (OR = .43, < .05) and the mid group (OR = .71, < .05) had a larger negative slope coefficient than the low group. This study found that LTPA participation reduces the risk of diabetes and gives evidence for the importance of cognitive function in reducing the prevalence of diabetes.
An Integrative Review of the Feasibility and Effects of the Use of Location-Tracking Devices by Persons Living With Cognitive Impairment
Kim J, Hwang M and Hwang Y
This study aimed to examine the effects of location-tracking devices on persons living with cognitive impairment, investigate facilitators of and barriers to using the devices, and provide future directions for the use of the devices.
Migration Inhibition Factor Secreted by Peripheral Blood Memory B Cells Binding to CD74-CD44 Receptor Complex Drives Macrophage Behavior in Alzheimer's Disease
Liu B, Luo W, Huang L, Wei C, Huang X, Liu J, Tao R, Mo Y and Li X
Dysregulation of the peripheral immune system is be involved in the neuroinflammation in Alzheimer disease (AD) and accelerate the disease progression. The contribution of immune cells, particularly B cells, to AD pathogenesis has gained attention in recent research. In this study, we investigated the role of Peripheral Blood Memory B cells (PBMBs) and their secreted Migration Inhibition Factor (MIF) in driving macrophage behavior in AD based on the scRNA-seq technique, immunofluorescence and flow cytometry. We discovered that MIF binds to the CD74-CD44 receptor complex on macrophages, influencing their behavior. The dysregulated macrophage response hampers the clearance of amyloid-beta (Aβ) plaques, exacerbating AD pathology. Targeting the MIF-CD74-CD44 signal pathway may hold therapeutic potential in modulating macrophage activity and mitigating neuroinflammation in AD. This study provides a further understanding of peripheral immune cells dysregulated in AD.
Birth Rate as a Determinant of Dementia Incidence: A Comprehensive Global Analysis
You W
The role of parity in predicting dementia risk in women is debated. This study examines how birth rate affects global dementia incidence.