Journal of Alzheimer's Disease - Volume 92, issue 3

Authors: Stites, Shana D. | Coe, Norma B.

Article Type: Review Article

Abstract: Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) research has advanced gene and biomarker technologies to aid identification of individuals at risk for dementia. This innovation is a lynchpin in development of disease-modifying therapies. The emerging science could transform outcomes for patients and families. However, current limitations in the racial representation and inclusion of racial diversity in research limits the relevance of these technologies: AD/ADRD research cohorts used to define biomarker cutoffs are mostly White, despite clinical and epidemiologic research that shows Black populations are among those experiencing the greatest burdens of AD/ADRD. White cohorts alone are insufficient to characterize …heterogeneity in disease and in life experiences that can alter AD/ADRD’s courses. The National Institute on Aging (NIA) has called for increased racial diversity in AD/ADRD research. While scientists are working to implement NIA’s plan to build more diverse research cohorts, they are also seeking out opportunities to consider race in AD/ADRD research. Recently, scientists have posed two ways of including race in AD/ADRD research: ancestry-based verification of race and race-based adjustment of biomarker test results. Both warrant careful examination for how they are impacting AD/ADRD science with respect to specific study objectives and the broader mission of the field. If these research methods are not grounded in pursuit of equity and justice, biases they introduce into AD/ADRD science could perpetuate, or even worsen, disparities in AD/ADRD research and care. Show more

Keywords: Alzheimer’s disease, biomarkers, genetics, preclinical Alzheimer’s, racism, scientific discoveries

DOI: 10.3233/JAD-220507

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 729-740, 2023

Authors: Sultana, Munira | Alexander, Neil | Pierucini-Faria, Frederico | Hunter, Susan W. | Kamkar, Nellie | Speechley, Mark R. | Son, Surim | Verghese, Joe | Montero-Odasso, Manuel

Article Type: Systematic Review

Abstract: Background: The prevalence of falls and related injuries is double in older adults with cognitive impairment compared with cognitively healthy older adults. A growing body of literature shows that falls prevention interventions in the cognitively impaired are difficult to implement and that the feasibility and adherence to interventions depend on a number of factors including informal caregiver involvement. However, no systematic review exists on the topic. Objective: Our objective is to determine whether involvement of informal caregivers can reduce falls in older adults with cognitive impairment. Methods: Rapid review following Cochrane collaboration guidelines. Results: …Seven randomized controlled trials were identified involving 2,202 participants. We identified the following areas where informal caregiving may have an important role in fall prevention in older adults with cognitive impairment: 1) enhancing adherence to the exercise program; 2) identifying and recording falls incidents and circumstances; 3) identifying and modifying possible environmental falls risk factors inside patient’s home; and 4) playing an active role in modifying lifestyle in terms of diet/nutrition, limiting antipsychotics, and avoiding movements risking falls. However, informal caregiver involvement was identified as an incidental finding in these studies and the level of evidence ranged from low to moderate. Conclusion: Informal caregiver involvement in planning and delivering interventions to reduce falls has been found to increase the adherence of individuals with cognitive impairment in falls prevention programs. Future research should address whether involvement of informal caregivers may improve efficacy of prevention programs by reducing the number of falls as a primary outcome. Show more

Keywords: Aged, caregivers, cognitive dysfunction, falls

DOI: 10.3233/JAD-221142

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 741-750, 2023

Authors: Swerdlow, Russell H.

Article Type: Review Article

Abstract: Viable Alzheimer’s disease (AD) hypotheses must account for its age-dependence; commonality; association with amyloid precursor protein, tau, and apolipoprotein E biology; connection with vascular, inflammation, and insulin signaling changes; and systemic features. Mitochondria and parameters influenced by mitochondria could link these diverse characteristics. Mitochondrial biology can initiate changes in pathways tied to AD and mediate the dysfunction that produces the clinical phenotype. For these reasons, conceptualizing a mitochondrial cascade hypothesis is a straightforward process and data accumulating over decades argue the validity of its principles. Alternative AD hypotheses may yet account for its mitochondria-related phenomena, but absent this happening a …primary mitochondrial cascade hypothesis will continue to evolve and attract interest. Show more

Keywords: Alzheimer’s disease, cascade, hypothesis, mitochondria

DOI: 10.3233/JAD-221286

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 751-768, 2023

Authors: Kania, Barbara | Sotelo, Alexis | Ty, Darren | Wisco, Jonathan J.

Article Type: Review Article

Abstract: The human gut microbiome consists of a variety of microorganisms that inhabit the intestinal tract. This flora has recently been shown to play an important role in human disease. The crosstalk between the gut and brain axis has been investigated through hepcidin, derived from both hepatocytes and dendritic cells. Hepcidin could potentially play an anti-inflammatory role in the process of gut dysbiosis through a means of either a localized approach of nutritional immunity, or a systemic approach. Like hepcidin, mBDNF and IL-6 are part of the gut-brain axis: gut microbiota affects their levels of expression, and this relationship is thought …to play a role in cognitive function and decline, which could ultimately lead to a number of neurodegenerative diseases such as Alzheimer’s disease. This review will focus on the interplay between gut dysbiosis and the crosstalk between the gut, liver, and brain and how this is mediated by hepcidin through different mechanisms including the vagus nerve and several different biomolecules. This overview will also focus on the gut microbiota-induced dysbiotic state on a systemic level, and how gut dysbiosis can contribute to beginnings and the progression of Alzheimer’s disease and neuroinflammation. Show more

Keywords: Brain, dysbiosis, hepcidin, high fat-high sugar diet, intestines, mBDNF, TMAO, vagus nerve, Western diet

DOI: 10.3233/JAD-220224

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 769-789, 2023

Authors: Wang, Zhe | Tan, Lin | Zong, Yu | Ma, Ya-Hui | Wang, Zhi-Bo | Wang, Hui-Fu | Tan, Lan

Article Type: Short Communication

Abstract: Defects in insulin-like growth factor 1 (IGF-1) signaling is a key contributor to Alzheimer’s disease (AD). However, the mechanism of how IGF-1 signaling relates to AD remained unclear. Here, we investigated the association of IGF-1 signaling associated biomarkers with AD pathology, sTREM2, and GFAP. Finally, insulin-like growth factor binding protein 2 (IGFBP-2) was associated with AD pathology, and the association was partly medicated by sTREM2 (Aβ42 , β= 0.794, p  = 0.016; T-tau, β= 0.291, p  < 0.001; P-tau181 , β= 0.031, p  < 0.001) and GFAP (T-tau, β= 0.427, p  < 0.001; P-tau181 , β= 0.044, p  < 0.001). It suggested that sTREM2 and GFAP mediated the relationship between …IGF-1 signaling and AD pathology. Show more

Keywords: AD pathology, Alzheimer’s disease, GFAP, IGF-1 signaling, IGFBP-2, sTREM2

DOI: 10.3233/JAD-220725

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 791-797, 2023

Authors: Atwood, Craig S. | Perry, George

Article Type: Article Commentary

Abstract: The questionable approval of aducanumab and the recent approval of lecanemab (Leqembi; Eisai and Biogen) by the FDA has raised the issue of safety (stroke, meningitis, and encephalitis) over efficacy (slowing of cognitive decline). This communication recounts the important physiological functions of amyloid-β as a barrier protein with unique sealant and anti-pathogenic activities important for maintaining vascular integrity coupled with innate immune functions that prevent encephalitis and meningitis. The approval of a drug that obviates both of these purposive functions increases the risk of hemorrhage, edema and downstream pathogenic outcomes and should be clearly outlined to patients.

Keywords: Adverse events, amyloid-β, ARIA, cognition, edema, hemorrhage, innate immunity, lecanemab, pathogen, stroke

DOI: 10.3233/JAD-230040

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 799-801, 2023

Authors: Kim, Bum Soo | Jun, Sungmin | Kim, Heeyoung

Article Type: Research Article

Abstract: Background: To diagnose mild cognitive impairment (MCI) patients at risk of progression to dementia is clinically important but challenging. Objective: We classified MCI patients based on cognitive trajectories and compared biomarkers among groups. Methods: This study analyzed amnestic MCI patients with at least three Clinical Dementia Rating (CDR) scores available over a minimum of 36 months from the Alzheimer’s Disease Neuroimaging Initiative database. Patients were classified based on their progression using trajectory modeling with the CDR-sum of box scores. We compared clinical and neuroimaging biomarkers across groups. Results: Of 569 eligible MCI patients (age …72.7±7.4 years, women n  = 223), three trajectory groups were identified: stable (58.2%), slow decliners (24.6%), and fast decliners (17.2%). In the fifth year after diagnosis, the CDR-sum of box scores increased by 1.2, 5.4, and 11.8 points for the stable, slow, and fast decliners, respectively. Biomarkers associated with cognitive decline were amyloid-β 42, total tau, and phosphorylated tau protein in cerebrospinal fluid, hippocampal volume, cortical metabolism, and amount of cortical and subcortical amyloid deposits. Cortical metabolism and the amount of amyloid deposits were associated with the rate of cognitive decline. Conclusion: Data-driven trajectory analysis provides new insights into the various cognitive trajectories of MCI. Baseline brain metabolism, and the amount of cortical and subcortical amyloid burden can provide additional information on the rate of cognitive decline. Show more

Keywords: Amyloid, Apolipoprotein E4, mild cognitive impairment, neurodegeneration, prognosis, putamen

DOI: 10.3233/JAD-220326

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 803-814, 2023

Authors: Calabria, Marco | Ciongoli, Francesco | Grunden, Nicholas | Ordás, Celia | García-Sánchez, Carmen

Article Type: Research Article

Abstract: Background: Recent research has shown that background music may improve memory consolidation and retrieval. Nevertheless, in the clinical conditions preceding dementia such as mild cognitive impairment (MCI), there is no current evidence speaking to what effect background music during memory tasks has on impaired cognition. Objective: Across three experiments, we investigated if background music is able to improve memory performance, the most impacted cognitive domain in amnestic MCI. Methods: We tested the effect of background music by using a face recognition memory task in patients with amnestic MCI. In Experiment 1, we tested the effect of …background music on memory when it was played solely during an encoding phase. In Experiment 2, we explored effects of background music when played during both encoding and recognition phases. In Experiment 3, we explored the role of musically induced arousal on memory. Results: The main finding from these three experiments was that background music played during a memory task did not improve or worsen participant performance. However, when exposed to high-arousal music, memory performance was predicted by individual mood regulation. For low-arousal music conditions, there was a negative relationship between rating scores for music pleasantness and performance on the memory task. Conclusion: Our results suggest that the benefits of background music on memory in individuals with MCI are modulated by interindividual preferences towards music. Show more

Keywords: Background music, cognitive stimulation, memory, mild cognitive impairment

DOI: 10.3233/JAD-221051

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 815-829, 2023

Authors: Engedal, Knut | Benth, Jūratė Šaltytė | Gjøra, Linda | Skjellegrind, Håvard Kjesbu | Nåvik, Marit | Selbæk, Geir

Article Type: Research Article

Abstract: Background: The Mini-Mental State Examination (MMSE), a simple test for measuring global cognitive function, is frequently used to evaluate cognition in older adults. To decide whether a score on the test indicates a significant deviation from the mean score, normative scores should be defined. Moreover, because the test may vary depending on its translation and cultural differences, normative scores should be established for national versions of the MMSE. Objective: We aimed to examine normative scores for the third Norwegian version of the MMSE. Methods: We used data from two sources: the Norwegian Registry of Persons Assessed …for Cognitive Symptoms (NorCog) and the Trøndelag Health Study (HUNT). After persons with dementia, mild cognitive impairment, and disorders that may cause cognitive impairment were excluded, the sample contained 1,050 cognitively healthy persons, 860 from NorCog, and 190 from HUNT, whose data we subjected to regression analyses. Results: The normative MMSE score varied from 25 to 29, depending on years of education and age. More years of education and younger age were associated with higher MMSE scores, and years of education was the strongest predictor. Conclusion: Mean normative MMSE scores depend on test takers’ years of education and age, with level of education being the strongest predictor. Show more

Keywords: Dementia, mild cognitive impairment, Mini-Mental State Examination, normative score

DOI: 10.3233/JAD-221068

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 831-842, 2023

Authors: Cascini, Silvia | Canevelli, Marco | Agabiti, Nera | Angelici, Laura | Davoli, Marina | Bacigalupo, Ilaria | Cova, Ilaria | Vanacore, Nicola | Pomati, Simone | Pantoni, Leonardo | Acampora, Anna | Bargagli, Anna Maria | Ancidoni, Antonio | Bacigalupo, Ilaria | Bellomo, Guido | Canevelli, Marco | Giusti, Angela | Lacorte, Eleonora | Palazzesi, Ilaria | Piscopo, Paola | Porrello, Mariacristina | Sciancalepore, Francesco | Vanacore, Nicola | Zambri, Francesca | Salvi, Emanuela | Acampora, Anna | Agabiti, Nera | Angelici, Laura | Bargagli, Anna Maria | Cascini, Silvia | Davoli, Marina | Cova, Ilaria | Maestri, Giorgia | Nicotra, Alessia | Pantoni, Leonardo | Pomati, Simone | Bruno, Giuseppe | Zaccaria, Valerio | Remoli, Giulia | Valletta, Martina | Di Blasio, Norina | De Fiore, Luca | Visco, Caterina

Article Type: Research Article

Abstract: Background: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients’ characteristics. Objective: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases. Methods: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in …migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients. Results: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14–1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54–0.67) and HMPCs (0.29%, 95% CI 0.27–0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians). Conclusion: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants. Show more

Keywords: Access to care, dementia, diversity, migrants, record linkage

DOI: 10.3233/JAD-221146

Citation: Journal of Alzheimer's Disease, vol. 92, no. 3, pp. 843-852, 2023