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Item Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.(Wiley Periodicals LLC on behalf of Alzheimer's Association, 2024-10-20) Lee W-P; Choi SH; Shea MG; Cheng P-L; Dombroski BA; Pitsillides AN; Heard-Costa NL; Wang H; Bulekova K; Kuzma AB; Leung YY; Farrell JJ; Lin H; Kunkle BW; Naj A; Blue EE; Nusetor F; Wang D; Boerwinkle E; Bush WS; Zhang X; De Jager PL; Dupuis J; Farrer LA; Fornage M; Martin E; Pericak-Vance M; Seshadri S; Wijsman EM; Wang L-S; Alzheimer's Disease Sequencing Project; Schellenberg GD; Destefano AL; Haines JL; Peloso GMINTRODUCTION Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. METHODS We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. RESULTS Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10−8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10−9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10−8). DISCUSSION We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD. Highlights We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.Item Effectiveness of dairy products to protect against cognitive decline in later life: a narrative review(Frontiers Media S.A., 2024-06-19) Anderson RC; Alpass FM; Drevenšek, GAs the world's population ages the prevalence of age-related health concerns is increasing, including neurodegeneration disorders such as mild cognitive impairment, vascular dementia and Alzheimer's disease. Diet is a key modifiable risk factor for the development of neurodegeneration, likely due to gut-brain axis interactions related to neuroinflammation. Analyses of dietary patterns identified dairy as being part of a cognitively healthy diet; however, its contribution to cognitive outcomes is difficult to discern. This narrative review evaluates the literature to determine whether there is sufficient evidence that the consumption of dairy products helps to maintain cognitive function in later life. A search using the terms (dairy OR milk OR cheese OR yogurt OR yogurt) AND ("mild cognitive impairment" OR dementia OR "Alzheimer's disease") identified 796 articles. After screening and sorting, 23 observational studies and 6 intervention studies were identified. The results of the observational studies implied that the relationship between total dairy consumption and cognitive outcomes is inverse U-shaped, with moderate consumption (1-2 servings per day) being the most beneficial. The analysis of the intake of different types of dairy products indicated that fermented products, particularly cheese, were most likely responsible for the observed benefits. The experimental studies all used dairy-derived peptides produced during fermentation as the dietary intervention, and the results indicated that these could be an effective treatment for early-stage cognitive impairment. Further experimental studies with whole dairy products, particularly fermented dairy, are needed to determine whether the regular consumption of these foods should be recommended to maximize the likelihood of healthy cognitive aging.Item Disentangling the relationship of subjective cognitive decline and depressive symptoms in the development of cognitive decline and dementia(Wiley Periodicals LLC on behalf of Alzheimer's Association, 2023-05) Kleineidam L; Wagner M; Guski J; Wolfsgruber S; Miebach L; Bickel H; König H-H; Weyerer S; Lühmann D; Kaduszkiewicz H; Luppa M; Röhr S; Pentzek M; Wiese B; Maier W; Scherer M; Kornhuber J; Peters O; Frölich L; Wiltfang J; Lewczuk P; Hüll M; Ramirez A; Jessen F; Riedel-Heller SG; Heser KIntroduction Subjective cognitive decline (SCD) and depressive symptoms (DS) frequently co-occur prior to dementia. However, the temporal sequence of their emergence and their combined prognostic value for cognitive decline and dementia is unclear. Methods Temporal relationships of SCD, DS and memory decline were examined by latent difference score modeling in a high-aged, population-based cohort (N = 3217) and validated using Cox-regression of dementia-conversion. In 334 cognitively unimpaired SCD-patients from memory-clinics, we examined the association of DS with cognitive decline and with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Results In the population-based cohort, SCD preceded DS. High DS were associated with increased risk of dementia conversion in individuals with SCD. In SCD-patients from memory-clinics, high DS were associated with greater cognitive decline. CSF Aß42 predicted increasing DS. Discussion SCD typically precedes DS in the evolution to dementia. SCD-patients from memory-clinics with DS may constitute a high-risk group for cognitive decline. Highlights Subjective cognitive decline (SCD) precedes depressive symptoms (DS) as memory declines. Emerging or persistent DS after SCD reports predict dementia. In SCD patients, more amyloid pathology relates to increasing DS. SCD patients with DS are at high risk for symptomatic progression.Item Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia.(John Wiley and Sons Inc on behalf of The Alzheimer's Association, 2019-03) Slot RER; Sikkes SAM; Berkhof J; Brodaty H; Buckley R; Cavedo E; Dardiotis E; Guillo-Benarous F; Hampel H; Kochan NA; Lista S; Luck T; Maruff P; Molinuevo JL; Kornhuber J; Reisberg B; Riedel-Heller SG; Risacher SL; Roehr S; Sachdev PS; Scarmeas N; Scheltens P; Shulman MB; Saykin AJ; Verfaillie SCJ; Visser PJ; Vos SJB; Wagner M; Wolfsgruber S; Jessen F; Alzheimer's Disease Neuroimaging Initiative; DESCRIPA working group; INSIGHT-preAD study group; SCD-I working group; van der Flier WMIntroduction In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini–Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.Item Emulsion-based delivery systems to improve gut and brain bioaccessibility of curcumin in relation to Alzheimer’s disease prevention : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Food Technology at Massey University, Palmerston North, New Zealand(Massey University, 2023) Lunelli, TacianaMedium chain triglycerides (MCT) from coconut oil, omega-3 polyunsaturated fatty acids from fish, phospholipids from dairy milk, and curcumin from turmeric all have been recognized for their anti-inflammatory and antioxidant properties. Curcumin is also a potential candidate for Alzheimer’s disease (AD) prevention; however, curcumin is poorly bioavailable unless emulsified. The milk fat globule membrane (MFGM) has natural emulsifying properties. I aimed to design an emulsion-based delivery system containing functional oils to encapsulate and deliver curcumin to the brain. I evaluated three commercial MFGM components with coconut and fish oils to produce emulsions with improved curcumin bioavailability. The emulsion structures were characterised by particle size, zeta-potential at the surface, microscopic structure, curcumin loading efficiency, and phospholipid distribution. All emulsions showed stable to particle size changes over 40 days at 4°C. Emulsion particle size decreased significantly with increasing concentrations of emulsifier, and presented negative zeta-potential varying from -50 to -20 mV, with the MFGM fractions creating significantly different charges and curcumin loading efficiency based on phospholipid and protein composition. All MFGM fractions efficiently created stable emulsions with small particle size and encapsulated curcumin. After simulated in vitro digestion, the emulsion with the highest phospholipid content had significantly higher curcumin bioaccessibility compared to the others. Fresh and digested emulsions and their components were assessed in the BE(2)-M17 neuroblastoma cell model for amyloid-β (Aβ) toxicity. Emulsions composed of both fish and coconut oils provided greater protection against Aβ toxicity compared to coconut oil alone. Curcumin was transported in vivo across the intestinal wall to the bloodstream and across the blood-brain barrier to the brain in rats fed all curcumin delivery formats. The kinetics of curcumin in blood and brain varied depending on the emulsion format. MFGM emulsions significantly reduced the curcumin and its metabolites peak time in blood and brain compared to the commercial curcumin preparation Meriva®, and all emulsions improved overall curcumin bioavailability and accumulation in the brain compared to free curcumin. A novel ex vivo approach using rat plasma samples directly in the neuroblastoma cell model requires further optimisation but demonstrated a significant interaction between gender and treatment on cell viability.Item The effect of encoding and retrieval manipulation on the retention of 'subject-performed tasks' in normal aging and Alzheimer's Disease : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Psychology at Massey University(Massey University, 1993) Sironen, PeggyThis research examined a technique termed ihe 'Subject-Performed Task' (SPT) in which subjects physically enact a verbal instruction and are subsequently administered recall tests to determine what information is retained. SPT is consistently found to produce superior recall to verbal instruction alone in several populations which experience memory difficulties with standard memory tasks, such as older adults and those with Alzheimer's Disease (DAT). The present study examined three issues, the first of which concerned what type(s) of information encoded in SPTs might be responsible for this effect. The second concerned the manner in which SPT was thought to instigate automatic activation of semantic category information. Finally, a comparison was made between DAT and older adult subjects to examine the ability of both groups to retain SPT information in memory. A total of 112 subjects (56 DAT subjects and 56 older adults) were presented with a series of 25 SPTs. The SPTs were presented visually and auditorally and were also demonstrated by an actor. Following presentation, subjects either performed the SPTs (motoric encoding condition) or verbally rehearsed (multisensory encoding condition) the randomly presented SPTs. Examination of automatic activation of semantic category information was assessed by comparing a relational recall condition which required categorisation of the SPTs into five semantic categories, with a free recall condition. DAT group subjects showed very low levels of recall and no significant effects of encoding or recall manipulations were found. The older adults showed higher levels of recall and both motoric encoding and relational recall enhanced performance. Reasons for the failure of DAT subjects to benefit from SPT are discussed, and the results obtained by the DAT group and the older adults are evaluated in the context of three predominant theories of SPT and memory.