Journal of Alzheimer's Disease - Volume 96, issue 1

Authors: Qeadan, Fares | McCunn, Ashlie | Tingey, Benjamin | Price Jr , Ron | Bobay, Kathleen L | English, Kevin | Madden, Erin F.

Article Type: Research Article

Abstract: Background: Past research suggests associations between heavy alcohol use and later life dementia. However, little is known about whether opioid use disorder (OUD) and dementia share this association, especially among age groups younger than 65 years old. Objective: Examine the association between OUD and Alzheimer’s disease (AD) and dementia. Methods: Electronic health records between 2000 and 2021 for patients age 12 or older were identified in the Cerner Real-World database™. Patients with a prior diagnosis of dementia were excluded. Patients were followed for 1-10 years (grouped by one, three, five, and ten-year follow-up periods) in a …matched retrospective cohort study. Cox proportional hazards regressions were used to estimate adjusted hazard ratios (aHRs) of incident AD/dementia stratified by age and follow-up group. Results: A sample of 627,810 individuals with OUD were compared to 646,340 without OUD. Individuals with OUD exhibited 88% higher risk for developing AD/dementia compared to those without OUD (aHR = 1.88, 95% CI 1.74, 2.03) within 1 year follow-up and 211% (aHR = 3.11, 95% CI 2.63, 3.69) within 10 years follow-up. When stratifying by age, younger patients (age 12-44) had a greater disparity in odds of AD/dementia between OUD and non-OUD groups compared with patients older than 65 years. Conclusions: Additional research is needed to understand why an association exists between OUD and AD/dementia, especially among younger populations. The results suggest that cognitive functioning screening programs for younger people diagnosed with OUD may be useful for targeting early identification and intervention for AD/dementia in particularly high risk and marginalized populations. Show more

Keywords: Alzheimer’s disease, cerner real-world data, cox proportional hazards, dementia, opioid use disorder

DOI: 10.3233/JAD-230714

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 229-244, 2023

Authors: Boulares, Ayoub | Fabre, Claudine | Cherni, Ala | Jdidi, Hela | Gaied Chortane, Sabri | Trompetto, Carlo | Puce, Luca | Bragazzi, Nicola Luigi

Article Type: Research Article

Abstract: Background: Aging often leads to cognitive function decline, sensory structure deterioration, and musculoskeletal system weakening. This impacts postural control during static and dynamic activities like walking, increasing the fall risk among the elderly. Older adults with mild cognitive impairment (MCI) face an elevated fall risk and cognitive decline, magnifying the public health concern. Objective: This study aimed to explore solutions by investigating the effects of a multi-component physical activity program on cognitive and motor functions in MCI patients. Methods: Twenty-three participants were enrolled in the study and assigned into two groups: an intervention group (n  = 13; …age = 85.7±5.5 years) and a control group (n  = 9; age = 85±6.7 years). The study spanned two months, with participants engaging in three 60-minute weekly physical exercise sessions. The intervention focused on improving proprioception, muscle strength, and balance. Results: Results demonstrated significant enhancements in physical performance, fall risk reduction, and balance (p  < 0.05). Various tests, including the timed up and go test, Unipedal Stance test, Tinetti test, Short Physical Performance Battery, and 6-minute walking test, indicated these improvements. Cognitive function was evaluated with the Mini-Mental State Examination, revealing non-significant progress (p  > 0.05). Predictive models for outcomes were developed using linear regression analysis during the follow-up stage. Conclusions: This study underscores the effectiveness of a multi-component physical activity program encompassing balance, proprioception, and muscle-strengthening exercises as a non-pharmaceutical approach in improving balance skills and playing a key role in mitigating the risk of falls among old adults with MCI. Show more

Keywords: Alzheimer’s disease, balance, cognitive functions, fall risk, mild cognitive impairment, motor functions, multi-component physical exercise, older adults, proprioception

DOI: 10.3233/JAD-230305

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 245-260, 2023

Authors: Lanza, Giuseppe

Article Type: Article Commentary

Abstract: In the relevant study by Boulares and colleagues, the importance of a multicomponent physical activity program in improving balance skills and leading to falling risk and fear reduction in older adults with mild cognitive impairment (MCI) is highlighted, despite the lack of cognitive effects. Given this apparent discrepancy between “body” and “mind” in MCI rehabilitation, the present commentary faces and discusses these findings within the existing literature and poses the question whether there were actually no cognitive results or if the program design and evaluation tool used were not sensitive enough to detect them, at least at this stage.

Keywords: Alzheimer’s disease, cognitive functions, mild cognitive impairment, motor functions, multicomponent physical exercise

DOI: 10.3233/JAD-230951

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 261-264, 2023

Authors: Utz, Janine | Olm, Pauline | Jablonowski, Johannes | Siegmann, Eva-Maria | Spitzer, Philipp | Lewczuk, Piotr | Kornhuber, Johannes | Maler, Juan Manuel | Oberstein, Timo Jan

Article Type: Research Article

Abstract: Background: The established Erlangen Score (ES) for the interpretation of cerebrospinal fluid (CSF) biomarkers in the diagnostics of Alzheimer’s disease (AD) uses markers of amyloidopathy and tauopathy, equally weighted to form an easy-interpretable ordinal scale. However, these biomarkers are not equally predictive for AD. Objective: The higher weighting of the Aβ42 /Aβ40 ratio, as a reconceptualized ERlangen Score (ERS), was tested for advantages in diagnostic performance. Methods: Non-demented subjects (N  = 154) with a mean follow up of 5 years were assigned to a group ranging from 0 to 4 in ES or ERS. Psychometric trajectories …and dementia risk were assessed. Results: The distribution of subjects between ES and ERS among the groups differed considerably, as grouping allocated 32 subjects to ES group 2, but only 2 to ERS group 2. The discriminative accuracy between the ES (AUC 73.2%, 95% CI [64.2, 82.2]) and ERS (AUC 72.0%, 95% CI [63.1, 81.0]) for dementia risk showed no significant difference. Without consideration of the Aβ42 /Aβ40 ratio in ES grouping, the optimal cut-off of the ES shifted to ≥2. Conclusions: The ERS showed advantages over the ES in test interpretation with comparable overall test performance, as fewer cases were allocated to the intermediate risk group. The established cut-off of ≥2 can be maintained for the ERS, whereas it must be adjusted for the ES when determining the Aβ42 /Aβ40 ratio. Show more

Keywords: Alzheimer’s disease, dementia risk, Erlangen Score, longitudinal study, neuropsychological trajectories

DOI: 10.3233/JAD-230524

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 265-275, 2023

Authors: Ding, Huitong | Mandapati, Amiya | Hamel, Alexander P. | Karjadi, Cody | Ang, Ting F.A. | Xia, Weiming | Au, Rhoda | Lin, Honghuang

Article Type: Research Article

Abstract: Background: Early prediction of dementia risk is crucial for effective interventions. Given the known etiologic heterogeneity, machine learning methods leveraging multimodal data, such as clinical manifestations, neuroimaging biomarkers, and well-documented risk factors, could predict dementia more accurately than single modal data. Objective: This study aims to develop machine learning models that capitalize on neuropsychological (NP) tests, magnetic resonance imaging (MRI) measures, and clinical risk factors for 10-year dementia prediction. Methods: This study included participants from the Framingham Heart Study, and various data modalities such as NP tests, MRI measures, and demographic variables were collected. CatBoost was …used with Optuna hyperparameter optimization to create prediction models for 10-year dementia risk using different combinations of data modalities. The contribution of each modality and feature for the prediction task was also quantified using Shapley values. Results: This study included 1,031 participants with normal cognitive status at baseline (age 75±5 years, 55.3% women), of whom 205 were diagnosed with dementia during the 10-year follow-up. The model built on three modalities demonstrated the best dementia prediction performance (AUC 0.90±0.01) compared to single modality models (AUC range: 0.82–0.84). MRI measures contributed most to dementia prediction (mean absolute Shapley value: 3.19), suggesting the necessity of multimodal inputs. Conclusion: This study shows that a multimodal machine learning framework had a superior performance for 10-year dementia risk prediction. The model can be used to increase vigilance for cognitive deterioration and select high-risk individuals for early intervention and risk management. Show more

Keywords: Alzheimer’s disease, dementia risk prediction, machine learning, magnetic resonance imaging, multimodal data, neuropsychological test

DOI: 10.3233/JAD-230496

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 277-286, 2023

Authors: Sun, Yifei | Moghekar, Abhay | Soldan, Anja | Pettigrew, Corinne | Greenberg, Barry | Albert, Marilyn | Wang, Mei-Cheng

Article Type: Research Article

Abstract: Background: Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are altered many years before the onset of clinical symptoms of mild cognitive impairment (MCI). Incorporating clinical symptom onset time into biomarker modeling may enhance our understanding of changes preceding MCI. Objective: Using a new analytical approach, we examined patterns of biomarker change prior to MCI symptom onset among individuals who progressed from normal cognition to MCI, stratified based on the age of symptom onset. We also analyzed biomarker patterns of change among participants who remained cognitively normal, and examined potential modifiers of biomarker trajectories, including demographics and apolipoprotein …E (APOE ) status. Methods: Analyses included 93 participants who progressed from normal cognition to MCI and 186 participants who remained cognitively normal, over an average follow-up period of 16.2 years. CSF biomarkers, including Aβ42 , Aβ40 , total tau (t-tau), and phosphorylated tau181 (p-tau181 ), were measured using the fully automated Lumipulse assays. Results: Among participants who progressed to MCI, Aβ42 /Aβ40 decreased, and t-tau and p-tau181 increased. For participants who did not progress to MCI, CSF biomarkers showed relatively stable patterns. In both progressors and non-progressors, APOE4 carriers showed lower Aβ 42 /Aβ40 levels (compared to non-carriers) at each point of the mean curves. Among non-progressors, APOE4 carriers had higher levels of p-tau181 , p-tau181 /(Aβ 42 /Aβ40 ), and t-tau/(Aβ 42 /Aβ 40 ). Additionally, among those who did not progress, female sex was associated with higher levels of t-tau, p-tau181 , t-tau/(Aβ 42 /Aβ 40 ), and p-tau181 /(Aβ 42 /Aβ 40 ). Conclusions: These findings suggest that this analytic approach may provide additional insights into biomarker changes during early phases of AD. Show more

Keywords: Alzheimer’s disease, amyloid, APOE genotype, biomarkers, cerebrospinal fluid, preclinical AD, tau

DOI: 10.3233/JAD-230807

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 287-300, 2023

Authors: Kero, Katherine | Halter, Colt M. | Moll, Allison C. | Hanna, Sophie M. | Woodard, John L. | Giordani, Bruno | Daugherty, Ana M. | Kavcic, Voyko

Article Type: Research Article

Abstract: Background: Cognitive assessment of older adults typically includes symptom reports and objective evaluations. However, there is often poor agreement between these measures. Cultural norms, stress, and anxiety may also influence cognitive self-appraisal and performance. Little research describes how other factors affect the self-report/objective test discrepancies noted in the literature. Objective: This study investigated whether the disparity between subjective cognitive concerns and objective cognitive performance is related to measures of anxiety and stress in older Black and African American adults. Methods: Telephone screenings were administered to 206 older adults (ages 64–94) during the first year of the …pandemic. Demographic data, objective memory (Telephone Interview for Cognitive Status [TICS-m]), an adaptation of the subjective memory measure, the Cognitive Change Questionnaire, emphasizing executive functioning in everyday life [CCQ-e]), Generalized Anxiety Disorder-7 (GAD-7), and Perceived Stress Scale-4 (PSS4) were measured. Metacognition Discrepancy Index (MDI) was calculated from the standardized residual after regressing TICS-m on CCQ-e scores to quantify the discrepancy between cognitive self-appraisal and objective cognitive functioning. Results: Neither GAD-7 nor PSS-4 moderated the relationship between TICS-m and CCQ-e, and TICS-m scores weakly predicted subjective CCQ-e scores (F (1, 197)=4.37, p  = 0.038, R2  = 0.022). The MDI correlated with stress and anxiety (rs  = 0.294, 0.396, ps  < 0.001). Conclusion: Discrepancies exist between objectively measured and self-evaluated cognition. Elevations in stress and anxiety are associated with greater overestimation of cognitive difficulties relative to objective performance. Pandemic-related stressors may have worsened anxiety and diminished self-appraisal of cognitive abilities for some individuals, while others may remain reluctant to acknowledge impairments. Social and emotional factors are meaningful considerations in assessing cognitive difficulties. Show more

Keywords: affect, Alzheimer’s disease, anxiety, cognitive decline, metacognition, psychological stress

DOI: 10.3233/JAD-221140

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 301-311, 2023

Authors: Chow, Tiffany E. | Veziris, Christina R. | Mundada, Nidhi | Martinez-Arroyo, Alexis I. | Kramer, Joel H. | Miller, Bruce L. | Rosen, Howard J. | Gorno-Tempini, Maria Luisa | Rankin, Katherine P. | Seeley, William W. | Rabinovici, Gil D. | La Joie, Renaud | Sturm, Virginia E.

Article Type: Research Article

Abstract: Background: In Alzheimer’s disease (AD), the gradual accumulation of amyloid-β (Aβ) and tau proteins may underlie alterations in empathy. Objective: To assess whether tau aggregation in the medial temporal lobes related to differences in cognitive empathy (the ability to take others’ perspectives) and emotional empathy (the ability to experience others’ feelings) in AD. Methods: Older adults (n  = 105) completed molecular Aβ positron emission tomography (PET) scans. Sixty-eight of the participants (35 women) were Aβ positive and symptomatic with diagnoses of mild cognitive impairment, dementia of the Alzheimer’s type, logopenic variant primary progressive aphasia, …or posterior cortical atrophy. The remaining 37 (22 women) were asymptomatic Aβ negative healthy older controls. Using the Interpersonal Reactivity Index, we compared current levels of informant-rated cognitive empathy (Perspective-Taking subscale) and emotional empathy (Empathic Concern subscale) in the Aβ positive and negative participants. The Aβ positive participants also underwent molecular tau-PET scans, which were used to investigate whether regional tau burden in the bilateral medial temporal lobes related to empathy. Results: Aβ positive participants had lower perspective-taking and higher empathic concern than Aβ negative healthy controls. Medial temporal tau aggregation in the Aβ positive participants had divergent associations with cognitive and emotional empathy. Whereas greater tau burden in the amygdala predicted lower perspective-taking, greater tau burden in the entorhinal cortex predicted greater empathic concern. Tau burden in the parahippocampal cortex did not predict either form of empathy. Conclusions: Across AD clinical syndromes, medial temporal lobe tau aggregation is associated with lower perspective-taking yet higher empathic concern. Show more

Keywords: Alzheimer’s disease, affective resonance, empathy, mentalization, social cognition, tau proteins

DOI: 10.3233/JAD-230367

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 313-328, 2023

Authors: Bramen, Jennifer E. | Siddarth, Prabha | Popa, Emily S. | Kress, Gavin T. | Rapozo, Molly K. | Hodes, John F. | Ganapathi, Aarthi S. | Slyapich, Colby B. | Glatt, Ryan M. | Pierce, Kyron | Porter, Verna R. | Wong, Claudia | Kim, Mihae | Dye, Richelin V. | Panos, Stella | Bookheimer, Tess | Togashi, Tori | Loong, Spencer | Raji, Cyrus A. | Bookheimer, Susan Y. | Roach, Jared C. | Merrill, David A.

Article Type: Research Article

Abstract: Background: A carbohydrate-restricted diet aimed at lowering insulin levels has the potential to slow Alzheimer’s disease (AD). Restricting carbohydrate consumption reduces insulin resistance, which could improve glucose uptake and neural health. A hallmark feature of AD is widespread cortical thinning; however, no study has demonstrated that lower net carbohydrate (nCHO) intake is linked to attenuated cortical atrophy in patients with AD and confirmed amyloidosis. Objective: We tested the hypothesis that individuals with AD and confirmed amyloid burden eating a carbohydrate-restricted diet have thicker cortex than those eating a moderate-to-high carbohydrate diet. Methods: A …total of 31 patients (mean age 71.4±7.0 years) with AD and confirmed amyloid burden were divided into two groups based on a 130 g/day nCHO cutoff. Cortical thickness was estimated from T1-weighted MRI using FreeSurfer. Cortical surface analyses were corrected for multiple comparisons using cluster-wise probability. We assessed group differences using a two-tailed two-independent sample t -test. Linear regression analyses using nCHO as a continuous variable, accounting for confounders, were also conducted. Results: The lower nCHO group had significantly thicker cortex within somatomotor and visual networks. Linear regression analysis revealed that lower nCHO intake levels had a significant association with cortical thickness within the frontoparietal, cingulo-opercular, and visual networks. Conclusions: Restricting carbohydrates may be associated with reduced atrophy in patients with AD. Lowering nCHO to under 130 g/day would allow patients to follow the well-validated MIND diet while benefiting from lower insulin levels. Show more

Keywords: Alzheimer’s disease, amyloid, atrophy, carbohydrates, carbohydrate-restricted, cerebral cortical thinning, cognitive dysfunction, diet, magnetic resonance imaging

DOI: 10.3233/JAD-230458

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 329-342, 2023

Authors: Sung, Wonjae | Kwon, Hyuk Sung | Park, Yeonjae | Kim, Seung Hyun | Park, Sojeong | Kang, Dae Ryong | Choi, Hojin

Article Type: Research Article

Abstract: Background: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported. Objective: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population. Methods: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether …there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout. Results: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7–60.2) to 69.9 (95% confidence interval: 65.3–74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia. Conclusions: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia. Show more

Keywords: Alzheimer’s disease, big data, dementia, gout, prevalence, uric acid

DOI: 10.3233/JAD-230468

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 343-349, 2023

Authors: Datlow, Lindsay Y. | King, Jay | Leventhal, Mark | Wallace, Taylor C.

Article Type: Research Article

Abstract: Background: Pork provides higher levels of several nutrients important for cognitive maintenance in older adults. A pilot clinical study suggests the addition of moderate amounts of pork to a Mediterranean-style diet improves cognition in older adults. There is an absence of observational research that isolates effects of pork from other red meats. Objective: To examine the relationship of pork intake on cognitive performance in older adults. Methods: Cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011–2014 cycles were used in these analyses. Pork intake was assessed using data from two non-consecutive 24-h …dietary recalls. Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning, CERAD Delayed Recall, Animal Fluency, and Digital Substitution tests. Statistical analyses were adjusted for sample weighting and survey design variables to account for the complex design. Student t -tests (continuous variables) and Pearson chi-squared tests (categorical variables) were employed to compare participant characteristics between the low and normal cognitive performance groups. Logistic regression was used to determine the relationship of pork intake (low, medium, and high) with prevalence of low cognitive performance, with the non-consumer group as the referent category. Results: Pork intake was not beneficially or detrimentally associated performance on the any of the cognitive tests in both the crude and multivariate models (p  > 0.05). Conclusions: Prospective cohort investigations and larger/longer-term clinical trials are needed to fully elucidate effects of pork intake on cognition in older adults. Show more

Keywords: Alzheimer’s disease, cognition, nutrition surveys, pork meat, red meat

DOI: 10.3233/JAD-230474

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 351-358, 2023

Authors: Zhu, Carolyn W. | Gu, Yian | Cosentino, Stephanie | Kociolek, Anton J. | Hernandez, Michelle | Stern, Yaakov

Article Type: Research Article

Abstract: Background: Misidentification of dementia in Medicare claims is quite common. Objective: We examined potential race/ethnic disparities in misidentification of dementia in Medicare claims in a diverse cohort of older adults who underwent careful clinical assessment. Methods: Participants were enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multiethnic, population-based, prospective study of cognitive aging in which dementia status was assessed using a rigorous clinical protocol. ICD-9-CM and ICD-10-CM diagnosis codes in all available Medicare claims (1999–2019) were compared to clinical dementia diagnosis and categorized into three mutually exclusive groups: 1) congruent-, 2) over-, and 3) …under- identification during the study period. Multinomial logistic regression model was used to examine the relationship between race (White, African American/Black, other) and ethnicity (Hispanic/Latinx, non-Hispanic/Latinx) and congruency of dementia identification after controlling for clinical (cognition, function, comorbidities) and demographic characteristics (age, sex, education), and inpatient and outpatient utilization. Results: Across all person-years, 88.4% had congruent identification of dementia compared to clinical diagnosis, in 4.1% of the times participants were over-identified with dementia, and 7.5% of the times the participants were under-identified. Rates of misidentification was higher in minority participants than in White, non-Hispanic participants. Multivariable estimation results showed that the probability of over-identification with dementia was 2.2% higher for African American/Black than White (p  = 0.05) and 2.7% higher for Hispanic participants than non-Hispanics (p  = 0.03) participants. Differences in under-identification by race/ethnicity were not statistically significant. Conclusions: African American/Black and Hispanic participants were more likely over-identified with dementia in Medicare claims. Show more

Keywords: Alzheimer’s disease, clinical diagnosis, disparities, Medicare claims

DOI: 10.3233/JAD-230584

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 359-368, 2023

Authors: Saji, Naoki | Ishihara, Yuichi | Murotani, Kenta | Uchiyama, Akira | Takeda, Akinori | Sakurai, Takashi | Matsushita, Kenji

Article Type: Research Article

Abstract: Background: Periodontal disease (PeD) is a risk factor of Alzheimer’s disease and is associated with cognitive decline in older adults. However, the relationships between subitems of neuropsychological tests and PeD have not been fully clarified. Objective: To evaluate associations between PeD and subitems of neuropsychological tests. Methods: We performed a cross-sectional analysis of data of 183 participants (women: 50%, mean age: 79 years) from a clinical study. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, neuropsychological tests, brain magnetic resonance images, and a dental screening check. We evaluated the relationships …between cognitive function and PeD using multivariable logistic regression analyses. Results: Participants with dementia were less likely to make periodical visits to the dentist, had fewer teeth, had less frequent tooth brushing habits, and were more likely to have PeD. Impaired cognitive function was significantly associated with an increasing degree of PeD. In multivariable logistic regression analyses, impaired visuospatial function and attention were associated with twice the risk of moderate or severe PeD compared with individuals with preserved visuospatial function and attention (odds ratio: 2.11, 95% confidence interval: 1.04–4.29, p  = 0.037). Impaired word recall and recognition and following commands were associated with increased risk of PeD (odds ratio: 2.80, 95% confidence interval: 1.41–5.32, p  = 0.003). Conclusions: Cognitive decline, such as impaired visuospatial function, attention, word recall and recognition, and inability to follow commands were independently and strongly associated with PeD. These items can be assessed easily on a daily basis. Show more

Keywords: Alzheimer’s disease, cognitive decline, dementia, oral health, periodontal disease, periodontitis

DOI: 10.3233/JAD-230742

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 369-380, 2023

Authors: Mehta, Kanika | Mohebbi, Mohammadreza | Pasco, Julie A. | Williams, Lana J. | Walder, Ken | Ng, Boon Lung | Gupta, Veer Bala

Article Type: Research Article

Abstract: Background: Poor cognitive function, a major disabling condition of older age, is often considered a prodromal feature of dementia. High mortality and the lack of a cure for dementia have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorders and bone loss have been previously linked with poor cognition individually although their combined effect remains largely unknown. Objective: Considering the multifactorial nature of dementia pathology, we investigated whether mood disorders, bone health and their interaction are associated with cognitive function in a population-based sample of men. …Methods: Four hundred and forty-two male participants were drawn from the Geelong Osteoporosis Study. Cognitive function was assessed using the CogState Brief Battery, which measured cognitive performance across four domains and was used to compute overall cognitive function. Mood disorders and hip bone mineral density (BMD) were determined using a semi-structured clinical interview and dual-energy X-ray absorptiometry, respectively. Results: Hip BMD (Bcoeff  = 0.56, 95% CI: [0.07, 1.05], p  = 0.025) but not mood disorder (Bcoeff  = –0.50, 95% CI: [–0.20, 0.10], p  = 0.529) was associated with overall cognitive function after accounting for potential confounders. Interaction effects were observed between the two exposures (Bcoeff  = –1.37, 95% CI: [–2.49, –0.26], p  = 0.016) suggesting that individuals without a mood disorder displayed better cognitive performance with increasing BMD, while those with a lifetime history of mood disorder displayed poorer cognitive function with increasing BMD. Conclusions: These findings highlight the importance of exploring interactions among potentially modifiable health conditions associated with cognitive function. Show more

Keywords: Alzheimer’s disease, bone mineral density, cognitive function, interaction, mood disorder

DOI: 10.3233/JAD-230140

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 381-393, 2023

Authors: Ikanga, Jean | Hickle, Sabrina | Schwinne, Megan | Epenge, Emmanuel | Gikelekele, Guy | Kavugho, Immaculee | Tsengele, Nathan | Samuel, Mampunza | Zhao, Liping | Qiu, Deqiang | Stringer, Anthony | Saindane, Amit M. | Alonso, Alvaro | Drane, Daniel L.

Article Type: Research Article

Abstract: Background: Western studies indicate potential associations between hippocampal volume and memory in the trajectory of Alzheimer’s disease (AD). However, limited availability of neuroimaging technology and neuropsychological tests appropriate for sub-Saharan African (SSA) countries makes it difficult to establish neuroanatomical associations of hippocampus and memory in this locale. Objective: This study examined hippocampal volumes and memory in healthy control (HC) and probable AD groups in the Democratic Republic of Congo (DRC). Methods: Forty-six subjects with probable AD and 29 HC subjects were screened using the Community Instrument for Dementia and the Alzheimer Questionnaire. Participants underwent neuroimaging in …Kinshasa, DRC, and memory was evaluated using the African Neuropsychology Battery (ANB). Multiple linear regression was used to determine associations between hippocampal volumes and memory. Results: Patients with probable AD performed significantly worse than HCs on ANB memory measures, and exhibited greater cerebral atrophy, which was significantly pronounced in the medial temporal lobe region (hippocampus, entorhinal cortex). Both AD and HC subjects exhibited high rates of white matter hyperintensities compared to international base rate prevalence, which was significantly worse for probable AD. Both also exhibited elevated rates of microhemorrhages. Regression analysis demonstrated a significant association between hippocampal volume and ANB memory tests. Hippocampal atrophy discriminated probable AD from the HC group. Conclusions: This study establishes the feasibility of conducting neuroimaging research in the SSA, demonstrates many known neuroimaging findings in probable AD patients hold up using culturally appropriate memory tasks, and suggest cardiovascular problems are a greater issue in SSA than in Western countries. Show more

Keywords: African Neuropsychology Battery, Alzheimer’s disease, dementia, hippocampus, magnetic resonance imaging, memory

DOI: 10.3233/JAD-230206

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 395-408, 2023

Authors: Pipingas, Andrew | Murphy, Karen J. | Davis, Courtney R. | Itsiopoulos, Catherine | Kingsley, Michael | Scholey, Andrew | Macpherson, Helen | Segal, Leonie | Breckon, Jeff | Minihane, Anne-Marie | Meyer, Denny | Ogden, Edward | Dyer, Kathryn A. | Eversteyn, Emily | Hardman, Roy J. | Poorun, Kaylass | Justice, Keri | Hana, Maher | Buckley, Jonathan D. | White, David | Davison, Kade | Clark, Jessie S. | Bracci, Ella L. | Kennedy, Greg

Article Type: Research Article

Abstract: Background: Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer’s disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive. Objective: The MedWalk trial’s primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment. Methods: MedWalk, a one-year cluster-randomized controlled trial …across two Australian states, recruited 60–90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation. Progress and Discussion: Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community. Trial registration: Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (https://www.anzctr.org.au ). Show more

Keywords: Alzheimer’s disease, cardiovascular, cluster-randomized clinical trial, cognition, cognitive behavioral therapy, dementia, exercise, Mediterranean diet, mood, motivational interviewing, physical activity

DOI: 10.3233/JAD-230641

Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 409-427, 2023