Journal of Alzheimer's Disease - Volume 94, issue 3

Article Type: Announcement

DOI: 10.3233/JAD-239005

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 859-860, 2023

Authors: Bayram, Ece | Holden, Samantha K. | Fullard, Michelle | Armstrong, Melissa J.

Article Type: Review Article

Abstract: Lewy body dementia is the third most common and costliest type of dementia. It is an umbrella term for dementia with Lewy bodies and Parkinson’s disease dementia, both of which place a substantial burden on the person and society. Recent findings outline ethnoracial differences in dementia risk. Delayed and misdiagnosis across ethnoracial groups contribute to higher levels of burden. In this context, we aimed to summarize current knowledge, gaps, and unmet needs relating to race and ethnicity in Lewy body dementia. In this narrative review, we provide an overview of studies on Lewy body dementia focusing on differences across ethnoracial …groups and outline several recommendations for future studies. The majority of the findings comparing different ethnoracial groups were from North American sites. There were no differences in clinical prevalence and progression across ethnoracial groups. Compared to people identifying as non-Hispanic White, co-pathologies were more common and clinical diagnostic accuracy was lower for people identifying as Black. Co-morbidities (e.g., diabetes, hypertension) were more common and medication use rates (e.g., antidepressants, antiparkinsonian agents) were lower for people identifying as Black or Hispanic compared to people identifying as White. More than 90% of clinical trial participants identified as non-Hispanic White. Despite increasing efforts to overcome disparities in Alzheimer’s disease and related dementias, inclusion of individuals from minoritized communities in Lewy body dementia studies continues to be limited and the findings are inconclusive. Representation of diverse populations is crucial to improve the diagnostic and therapeutic efforts in Lewy body dementia. Show more

Keywords: Alzheimer’s disease, dementia, diversity, equity, ethnicity, inclusion, Lewy body disease, racial groups

DOI: 10.3233/JAD-230207

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 861-878, 2023

Authors: Panza, Francesco | Solfrizzi, Vincenzo | Sardone, Rodolfo | Dibello, Vittorio | Castellana, Fabio | Zupo, Roberta | Stallone, Roberta | Lampignano, Luisa | Bortone, Ilaria | Mollica, Anita | Berardino, Giuseppe | Ruan, Qingwei | Altamura, Mario | Bellomo, Antonello | Daniele, Antonio | Lozupone, Madia

Article Type: Review Article

Abstract:  In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The …biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality. Show more

Keywords: Alzheimer’s disease, cognitive frailty, dementia, frailty, lifestyle, mild cognitive impairment, physical frailty, social frailty, vascular dementia

DOI: 10.3233/JAD-230312

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 879-898, 2023

Authors: Wang, Ge | Li, Daniel Y. | Vance, David E. | Li, Wei

Article Type: Systematic Review

Abstract: Background: Alcohol use disorder (AUD) is a worldwide problem. The AUD can take the form of hazardous drinking, binge drinking, or alcohol dependence. The effects of alcohol on cognition can be diverse and complex. Objective: Our study aimed to assess AUD as a risk factor for cognitive impairment. Methods: A literature search was conducted using major electronic databases of PubMed, EMBASE, and Web of Science. Abstracts were screened independently to include data from original research reports. The following keywords were used: alcohol abuse, cognitive impairment, Alzheimer’s disease, and dementia. In total, 767 abstracts were retrieved. After …removing the duplicates, 76 articles met the criteria for full-text review, of which 41 were included in this report. Results: People with AUD are seen from different geographical areas and cultures. AUD is associated with an increased risk of cognitive impairments, Alzheimer’s disease, and dementia, especially vascular dementia. In addition, AUD interacts with comorbidities increasing the risk of cognitive impairment. Conclusion: AUD is associated with an increased risk of cognitive impairments, which may have more than one underlying mechanism. Show more

Keywords: Alcohol use disorder, Alzheimer’s disease, cognitive impairment, dementia

DOI: 10.3233/JAD-230181

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 899-907, 2023

Authors: Saúde, Alexandra | Bouça-Machado, Raquel | Leitão, Mariana | Benedetti, Andrea | Ferreira, Joaquim J.

Article Type: Systematic Review

Abstract: Background: Physiotherapy has become increasingly relevant as a new therapeutic intervention for dementia. However, it is unclear which interventions are the most suitable. Objective: This study sought to summarize and critically appraise the evidence on physiotherapy interventions in dementia. Methods: A systematic review conducted using CENTRAL, MEDLINE, and PEDro databases, from their inception to July 2022, identified all experimental studies of dementia that included physiotherapy interventions. Results: Of 194 articles included, the most frequently used interventions were aerobic training (n  = 82, 42%), strength training (n  = 79, 41%), balance training (n  = 48, 25%), and stretching …(n  = 22, 11%). These were associated with a positive effect on several motor and cognitive outcomes. A total number of 1,119 adverse events were reported. Conclusion: Physiotherapy has several motor and cognitive benefits in dementia. Future research should focus on establishing a physiotherapy prescription protocol for people with mild cognitive impairment and for each stage of dementia. Show more

Keywords: Alzheimer’s disease, clinical exercise, dementia, motor function, physiotherapy

DOI: 10.3233/JAD-230463

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 909-917, 2023

Authors: Fu, Xin-Xin | Wei, Bin | Cao, Hai-Ming | Duan, Rui | Deng, Yang | Lian, Hui-Wen | Zhang, Ying-Dong | Jiang, Teng

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the most common type of neurodegenerative disorder. There are few effective medications for halting the progression of AD. Telmisartan (TEL) is a widely used anti-hypertensive drug approved by FDA. Aside from treating hypertension, TEL has been revealed to provide protection against AD. However, the underlying mechanisms remain unclear. Objective: To investigate the mechanisms underlying the beneficial effects of TEL against AD. Methods: Eight-month-old APP/PS1 mice were administered with 5 mg/kg TEL once per day for 4 successive months. Nesting test, Y-maze test, and Morris water maze test were employed to assess the …cognitive and executive functions. Neuronal and synaptic markers, amyloid-β (Aβ) pathology, neuroinflammation, and oxidative stress in the brains were measured. Specifically, components involved in Aβ production and degradation pathway were analyzed to explore the mechanisms underlying the therapeutic effect of TEL against Aβ pathology. The primary microglia were used to uncover the mechanisms underlying the anti-inflammatory effects of TEL in AD. Additionally, the preventive effect of TEL against AD were investigated using 4-month-old APP/PS1 mice. Results: TEL treatment ameliorated cognitive and executive impairments, neuronal and synaptic injury, Aβ pathology, neuroinflammation, and oxidative stress in APP/PS1 mice. The favorable effects of TEL on Aβ pathology were achieved by inhibiting enzymatic Aβ production and facilitating enzymatic and autophagic Aβ degradation. Meanwhile, the anti-inflammatory effects of TEL were accomplished via microglial PPARγ /NLRP3 pathway. The administration of TEL prior to symptom onset prevented AD-related cognitive decline and neuropathologies. Conclusion: TEL represents a promising agent for AD prevention and treatment. Show more

Keywords: Alzheimer’s disease, amyloid-β pathology, autophagy, cognitive and executive impairments, neuroinflammation, neuronal and synaptic injury, NLRP3, oxidative stress, PPARγ , telmisartan

DOI: 10.3233/JAD-230133

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 919-933, 2023

Authors: Heger, Irene | Deckers, Kay | de Vugt, Marjolein | Verhey, Frans | Oenema, Anke | van Boxtel, Martin | Köhler, Sebastian

Article Type: Research Article

Abstract: Background: Health- and lifestyle factors account for a substantial part of all dementia cases, which opens the opportunity for primary prevention. However, the required behavioral change is complex and involves targeting multiple risk factors. mHealth interventions can potentially contribute to improving motivation in a low-cost and scalable way. Objective: To explore usage patterns, appreciation, and beliefs and attitudes regarding dementia risk reduction during the use of the MyBraincoach mobile app. Methods: Participants were community-dwelling middle-aged adults from the Netherlands and used either the standard (education) or extended (education+motivational triggers) app version for three months. Two panel …studies were combined in this paper. Chi-square tests, t -tests and linear mixed models were used, adjusted for age, sex, and education. Results: Of all participants (n  = 299, 50.2% male), 167 (55.9%) had installed the app. The most reported reason for non-use was technical problems (47%). Those who used the app were at baseline already more positive about dementia risk reduction than those who did not use the app. Of all users who completed the evaluation (n  = 102), 78.4% (n  = 80) stated that the app provided a positive approach towards brain health and 80.4% (n  = 82) felt better informed. Younger (<60y) and lower educated participants evaluated the app most positively. Conclusion: Usage of the app was low, but users showed more positive beliefs and attitudes regarding dementia risk reduction. Most users evaluated the app positively and stated to have gained knowledge on the topic. Improving the use of the app must keep high priority in future studies. Show more

Keywords: Alzheimer’s disease, awareness, dementia, mobile applications, primary prevention, protective factors, public health, risk assessment, risk factors, risk reduction behavior

DOI: 10.3233/JAD-230225

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 935-948, 2023

Authors: Zakharova, Alena | Kitamura, Kaori | Watanabe, Yumi | Kabasawa, Keiko | Takahashi, Akemi | Saito, Toshiko | Kobayashi, Ryosaku | Oshiki, Rieko | Takachi, Ribeka | Tsugane, Shoichiro | Yamazaki, Osamu | Watanabe, Kei | Nakamura, Kazutoshi

Article Type: Research Article

Abstract: Background: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex. Objective: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people. Methods: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40–74 years at baseline in 2011–2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5–20.6 (low-normal), …20.7–22.6 (mid-normal), 22.7–24.9 (high-normal), 25.0–29.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs). Results: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the “underweight,” “low-normal,” and “overweight” groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference (“high-normal” group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period. Conclusion: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia. Show more

Keywords: Alzheimer’s disease, body mass index, cohort study, dementia, risk factor, sex difference, waist circumference

DOI: 10.3233/JAD-230294

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 949-959, 2023

Authors: Kostev, Karel

Article Type: Article Commentary

Abstract: In this issue, Zakharova et al. report on important findings concerning the association between body mass index and dementia risk as related to sex. Concretely, underweight was strongly associated with dementia risk in men but not in women. We compare the results of this study with a recent publication by Jacob et al. and consider the role of sex in the association between body mass index and dementia.

Keywords: Alzheimer’s disease, body mass index, dementia, sex, underweight

DOI: 10.3233/JAD-230598

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 961-962, 2023

Authors: Cubero-Plazas, Laura | Sancho-Cantus, David | de la Rubia Ortí, José Enrique | Prieto-Contreras, Lucía | Forero-Rincón, Olga | Cunha-Pérez, Cristina

Article Type: Research Article

Abstract: Background: Dementia is one of the pathologies that has increased the most among the older population (mainly Alzheimer’s disease), and it has a direct impact on the quality of life (QoL), cognitive performance, and health of these patients. Family functionality can play a role in this QoL if these patients are not institutionalized. Objective: To analyze the role of family function in the QoL and health perception of non-institutionalized dementia patients, as well as related variables such as anxiety, depression, optimism, or pessimism. Methods: Cross-sectional study with a sample of 54 patients diagnosed with some type …of dementia, non-institutionalized, or in outpatient care, from different centers in the province of Valencia (Spain). The EQ-5D, MMSE, Apgar Family or general health, and Goldberg anxiety and depression questionnaires were utilized. Results: The correlation of the Apgar Family with the General Health Questionnaire-new onset problems variable (GHQ) and Chronicity and General Health Questionnaire-chronic problems (CGHQ) of the Goldberg Quality of Life questionnaire was statistically significant and negative (GHQ r  = –0.310; p  = 0.034. CGHQ r  = –0.363; p  = 0.012); as well as between Apgar Family and Anxiety-Depression (r  = –0.341; p  = 0.020). The correlation of the Apgar Family with the Life Orientation Test-Pessimism variable (LOT) was statistically significant and negative (r  = –0.270; p  = 0.061). Finally, severe dysfunction of Apgar Family has a negative correlation with self-perception of health (p  = 0.036 B  = –16.589) determined by the Visual Analogue Scale (VAS). Conclusion: Family functionality directly influences anxiety, depression, optimism, and pessimism. This could explain why family function is related to the QoL of patients and their self-perception of health. Show more

Keywords: Alzheimer’s disease, anxiety, dementia, depression, family dynamics, health perception, non-institutionalized elderly, quality of life

DOI: 10.3233/JAD-230324

Citation: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 963-975, 2023