Journal of Alzheimer's Disease - Volume 94, issue 2

Authors: Farina, Francesca R. | Booi, Laura | Occhipinti, Jo-An | Quoidbach, Vinciane | Destrebecq, Frédéric | Muniz-Terrera, Graciela | Eyre, Harris A.

Article Type: Review Article

Abstract: The potential for future prevention of Alzheimer’s disease and related dementias (ADRD) through healthy lifestyle change is spurring a positive brain health movement. However, most ADRD research continues to focus on mid- and later life. We lack evidence regarding risk exposure and protective factors in young adulthood, i.e., 18–39 years. Brain capital is an emerging framework that represents the combination of education, knowledge, skills, and optimal brain health that people accumulate over their lives. Building on this framework, we present a new model that focuses on optimizing brain health in young adulthood; namely, young adult brain capital. Increasing focus on …younger populations is critical for developing citizens who are emotionally intelligent, resilient and can anticipate and cope with rapid changes in the world. By understanding the values that are key drivers and motivators for young adults, we can empower the next generation to become active agents in optimizing their brain health and reducing their risk for future ADRD. Show more

Keywords: Alzheimer’s disease, brain capital, brain health, prevention, risk reduction, young adults

DOI: 10.3233/JAD-230260

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 415-423, 2023

Authors: Garrido-Dzib, Angel Gabriel | Chávez-Loría, Geovanni | Magallón-Zertuche, Valeria | Avila-Nava, Azalia | Palacios-González, Berenice | Gutiérrez-Solis, Ana Ligia

Article Type: Systematic Review

Abstract: Background: Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have. Objective: The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia. Methods: A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot. Results: Nine articles …were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07–1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07–83.2) of protein; 262.17 g/day (95% CI 214.51–309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16–66.66) of fats were reported. A micronutrients daily intake consumption of 201.35μg/day of vitamin B9 (95% CI 125.32–277.38); 5.61μg/day of vitamin B12 (95% CI 2.53–8.70), and 139.67 mg/day of vitamin C (95% CI 59.33–220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54–986.11) and 9 mg/day of iron (95% CI 2.28–15.71) was obtained. A low intake of fruits and vegetables was found. Conclusion: Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium. Show more

Keywords: Alzheimer’s disease, cognitive impairment, dementia, diet, intake, Latin American countries, nutrition

DOI: 10.3233/JAD-230231

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 425-439, 2023

Authors: Sun, Lina | Ye, Kaisy Xinhong | Wong, Hoi Lin Kathleen | Wang, Lingyan | Lim, Su Lin | Chao, Yin Xia | Zhang, Can | Yap, Kai Zhen | Feng, Lei

Article Type: Systematic Review

Abstract: Background: The current lack of effective drug therapies for Alzheimer’s disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. Objective: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. Methods: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n  = 10 …studies) met the inclusion criteria. Results: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOE ɛ 4 (−) subjects than APOE ɛ 4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). Conclusion: This review provides some evidence that treatment with MCT could improve general cognitive function in APOE ɛ 4 (−) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management. Show more

Keywords: Alzheimer’s disease, cognitive impairment, medium chain triglyceride, mild cognitive impairment, systematic review

DOI: 10.3233/JAD-230406

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 441-456, 2023

Authors: Rudge, Jonathan D’Arcy

Article Type: Research Article

Abstract: The Lipid Invasion Model (LIM) is a new hypothesis for Alzheimer’s disease (AD) which argues that AD is a result of external lipid invasion to the brain, following damage to the blood-brain barrier (BBB). The LIM provides a comprehensive explanation of the observed neuropathologies associated with the disease, including the lipid irregularities first described by Alois Alzheimer himself, and accounts for the wide range of risk factors now identified with AD, all of which are also associated with damage to the BBB. This article summarizes the main arguments of the LIM, and new evidence and arguments in support of it. …The LIM incorporates and extends the amyloid hypothesis, the current main explanation of the disease, but argues that the greatest cause of late-onset AD is not amyloid-β (Aβ) but bad cholesterol and free fatty acids, let into the brain by a damaged BBB. It suggests that the focus on Aβ is the reason why we have made so little progress in treating the disease in the last 30 years. As well as offering new perspectives for further research into the diagnosis, prevention, and treatment of AD, based on protecting and repairing the BBB, the LIM provides potential new insights into other neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis/motor neuron disease. Show more

Keywords: Alzheimer’s disease, amyloid, apolipoproteins, blood-brain barrier, cholesterol, ethanol, lipids, lipoproteins, neurofibrillary tangles, nonesterified fatty acids, plaque

DOI: 10.3233/JAD-221175

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 457-470, 2023

Authors: Hansen, Scott B.

Article Type: Article Commentary

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder associated with neuroinflammation and altered lipids in the brain. Cholesterol is a key component of inflammatory lipids. However, the role of cholesterol in AD, specifically in sporadic or late-onset AD, has remained poorly understood due to the belief that most brain cholesterol is separate from circulating blood cholesterol. A new theory suggests that the permeation of circulating cholesterol into the brain is a causal event critical for the onset of AD. As research in this area continues, new hypotheses and insights into AD are expected to emerge.

Keywords: Alzheimer’s disease, apoE, blood-brain barrier, cholesterol, lipids, neuroinflammation

DOI: 10.3233/JAD-230538

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 471-472, 2023

Authors: Hazan, Jemma | Liu, Kathy Y. | Fox, Nick | Howard, Robert

Article Type: Research Article

Abstract:  Changes in diagnostic certainty can be evaluated by assessing the impact of a diagnostic test in driving decision making. Diagnostic tests can be appraised using validated measures of accuracy, i.e., sensitivity, specificity, and positive or negative predictive values against a known reference standard. However, other less well formalized factors affect diagnostic certainty. These inputs are under-researched and more difficult to quantify. Clinicians assess the significance of available data in the context of their expertise, pre-diagnostic confidence, and background knowledge of populations and disease. Inherent qualities of the diagnostic test and an individual clinician’s interpretation of the meaning of test results …will also affect the subsequent level of diagnostic certainty. These factors are only infrequently considered alongside the diagnostic accuracy of a test. In this paper, we present a model of the different processes which can affect diagnostic certainty in Alzheimer’s disease (AD). This model builds upon existing understanding and provides further insights into the complexity of diagnostic certainty in AD and how we might improve this. Show more

Keywords: Alzheimer’s disease, biomarkers, dementia, diagnosis, investigations, mild cognitive impairment

DOI: 10.3233/JAD-230186

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 473-482, 2023

Authors: Patel, Smita | Wei, Jun | Shi, Zhuqing | Rifkin, Andrew S. | Zheng, S. Lilly | Gelfman, Elizabeth | Duggan, David | Helfand, Brian T. | Hulick, Peter J. | Xu, Jianfeng

Article Type: Short Communication

Abstract: In a large population-based cohort, we show not all heterozygous APOE ɛ 4 carriers are at increased risk for Alzheimer’s disease (AD); a significantly higher AD proportion was only found for ɛ 3/ɛ 4, not ɛ 2/ɛ 4. Among ɛ 3/ɛ 4 carriers (24% in the cohort), the AD proportion differed considerably by polygenic risk score (PRS). In particular, the AD proportion was lower than the entire cohort for subjects in the bottom 20-percentile PRS and was higher than that of homozygous ɛ 4 carriers for subjects at the top 5th-percentile PRS. Family history was no longer a significant …predictor of AD risk after adjusting APOE and PRS. Show more

Keywords: Alzheimer’s disease, APOE , genetic counseling, polygenic risk score, UK Biobank

DOI: 10.3233/JAD-230156

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 483-489, 2023

Authors: Avila, Jesús | Perry, George

Article Type: Article Commentary

Abstract:  Memory consolidation related to the hippocampal-cortex connection takes place during sleep. This connection may involve at least two steps— one in the NREM phase of sleep (transmission) and the other in the REM phase (consolidation). In this brief report, we comment on the role of tau protein in these two phases of sleep. The absence of tau decreases δ waves in NREM, whereas the overexpression of modified (phosphorylated and/or mutated) tau alters θ waves in REM.

Keywords: Alzheimer’s disease, delta waves, memory, NREM phase, sleep, tau

DOI: 10.3233/JAD-230230

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 491-495, 2023

Authors: Kepp, Kasper P. | Sensi, Stefano L. | Johnsen, Kasper B. | Barrio, Jorge R. | Høilund-Carlsen, Poul F. | Neve, Rachael L. | Alavi, Abass | Herrup, Karl | Perry, George | Robakis, Nikolaos K. | Vissel, Bryce | Espay, Alberto J.

Article Type: Article Commentary

Abstract: After the CLARITY-AD clinical trial results of lecanemab were interpreted as positive, and supporting the amyloid hypothesis, the drug received accelerated Food and Drug Administration approval. However, we argue that benefits of lecanemab treatment are uncertain and may yield net harm for some patients, and that the data do not support the amyloid hypothesis. We note potential biases from inclusion, unblinding, dropouts, and other issues. Given substantial adverse effects and subgroup heterogeneity, we conclude that lecanemab’s efficacy is not clinically meaningful, consistent with numerous analyses suggesting that amyloid-β and its derivatives are not the main causative agents of Alzheimer’s disease …dementia. Show more

Keywords: Alzheimer’s disease, amyloid-β , antibody, lecanemab, subgroup analysis

DOI: 10.3233/JAD-230099

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 497-507, 2023

Authors: Mattace-Raso, Francesco | Goudzwaard, Jeannette A. | Polinder-Bos, Harmke A. | Tap, Lisanne

Article Type: Article Commentary

Abstract: Current guidelines on cardiovascular risk management are extrapolated to all older adults. It is, however, highly debatable whether recommendations also apply for patients with dementia since previous studies have not included this specific population. Time to benefit as well as higher risk of adverse events play a crucial role in the decision process of prescribing or deprescribing. Regular monitoring is needed in older patients with dementia, in order to make individual-based treatment strategies. Cardiovascular risk management in older patients with dementia should focus on quality of life, preventing cognitive and functional deterioration, and maintaining independence.

Keywords: Alzheimer’s disease, cardiovascular disease, cardiovascular risk management, dementia

DOI: 10.3233/JAD-230382

Citation: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 509-512, 2023