Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance

Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria.A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity.The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination

Rosiglitazone Inhibits Transforming Growth Factor-β1 Mediated Fibrogenesis in ADPKD Cyst-Lining Epithelial Cells

BACKGROUND: Interstitial fibrosis plays an important role in progressive renal dysfunction in autosomal dominant polycystic kidney disease (ADPKD). In our previous studies, we confirmed that PPAR-γ agonist, rosiglitazone could protect renal function and prolong the survival of a slowly progressive ADPKD animal model by reducing renal fibrosis. However, the mechanism remains unknown. METHODS: Primary culture epithelial cells pretreated with TGF-β1 were incubated with rosiglitazone. Extracellular matrix proteins were detected using real-time PCR and Western blotting. MAPK and Smad2 phosphorylation were measured with western blot. ERK1/2 pathway and P38 pathway were inhibited with the specific inhibitors PD98059 and SB203580. The Smad2 pathway was blocked with the siRNA. To address whether PPAR-γ agonist-mediated inhibition of TGF-β1-induced collagen type I expression was mediated through a PPAR-γ dependent mechanism, genetic and pharmaceutical approaches were used to block the activity of endogenous PPARγ. RESULTS: TGF-β1-stimulated collagen type I and fibronectin expression of ADPKD cyst-lining epithelia were inhibited by rosiglitazone in a dosage-dependent manner. Smad2, ERK1/2 and P38 pathways were activated in response to TGF-β1; however, TGF-β1 had little effect on JNK pathway. Rosiglitazone suppressed TGF-β1 induced Smad2 activation, while ERK1/2 and P38MAPK signals remained unaffected. Rosiglitazone could also attenuate TGF-β1-stimulated collagen type I and fibronectin expression in primary renal tubular epithelial cells, but had no effect on TGF-β1-induced activation of Smad2, ERK1/2 and P38 pathways. There was no crosstalk between the Smad2 and MAPK pathways in ADPKD cyst-lining epithelial cells. These inhibitory effects of rosiglitazone were reversed by the PPARγ specific antagonist GW9662 and PPARγ siRNA. CONCLUSION: ADPKD cyst-lining epithelial cells participate in TGF-β1 mediated fibrogenesis. Rosiglitazone could suppress TGF-β1-induced collagen type I and fibronectin expression in ADPKD cyst-lining epithelia through modulation of the Smad2 pathway. Our study may provide therapeutic basis for clinical applications of rosiglitazone in retarding the progression of ADPKD

Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques

Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development

Sociodemographic inequities associated with participation in leisure-time physical activity in sub-Saharan Africa: an individual participant data meta-analysis

Abstract: Background: Leisure-time physical activity (LTPA) is an important contributor to total physical activity and the focus of many interventions promoting activity in high-income populations. Little is known about LTPA in sub-Saharan Africa (SSA), and with expected declines in physical activity due to rapid urbanisation and lifestyle changes we aimed to assess the sociodemographic differences in the prevalence of LTPA in the adult populations of this region to identify potential barriers for equitable participation. Methods: A two-step individual participant data meta-analysis was conducted using data collected in SSA through 10 population health surveys that included the Global Physical Activity Questionnaire. For each sociodemographic characteristic, the pooled adjusted prevalence and risk ratios (RRs) for participation in LTPA were calculated using the random effects method. Between-study heterogeneity was explored through meta-regression analyses and tests for interaction. Results: Across the 10 populations (N = 26,022), 18.9% (95%CI: 14.3, 24.1; I2 = 99.0%) of adults (≥ 18 years) participated in LTPA. Men were more likely to participate in LTPA compared with women (RR for women: 0.43; 95%CI: 0.32, 0.60; P < 0.001; I2 = 97.5%), while age was inversely associated with participation. Higher levels of education were associated with increased LTPA participation (RR: 1.30; 95%CI: 1.09, 1.55; P = 0.004; I2 = 98.1%), with those living in rural areas or self-employed less likely to participate in LTPA. These associations remained after adjusting for time spent physically active at work or through active travel. Conclusions: In these populations, participation in LTPA was low, and strongly associated with sex, age, education, self-employment and urban residence. Identifying the potential barriers that reduce participation in these groups is necessary to enable equitable access to the health and social benefits associated with LTPA

Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells

The notion that the differentiated state of a cell population is determined simply by expression of specific marker genes is changing. In this work, the authors reveal that a pluripotent cell population comprises cells with temporal fluctuations in the expression of Nanog

Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer's Disease

Background: Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p&lt;0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p&lt;0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Ultrasound-assisted extraction of natural products

Ultrasound-assisted extraction (USAE) is an interesting process to obtain high valuable compounds and could contribute to the increase in the value of some food by-products when used as sources of natural compounds. The main benefits will be a more effective extraction, thus saving energy, and also the use of moderate temperatures, which is beneficial for heat-sensitive compounds. For a successful application of the USAE, it is necessary to consider the influence of several process variables, the main ones being the applied ultrasonic power, the frequency, the extraction temperature, the reactor characteristics, and the solvent-sample interaction. The highest extraction rate is usually achieved in the first few minutes, which is the most profitable period. To optimize the process, rate equations and unambiguous process characterization are needed, aspects that have often been lacking. © 2011 Springer Science+Business Media, LLC.The authors thank the Generalitat Valenciana for their financial support in project PROMETEO/2010/062 and the Caja de Ahorros del Mediterraneo for M.D. Esclapez's pre-doctoral grant.Esclapez Vicente, MD.; García Pérez, JV.; Mulet Pons, A.; Cárcel Carrión, JA.; Esclapez, MD. (2011). Ultrasound-assisted extraction of natural products. Food Engineering Reviews. 3(2):108-120. https://doi.org/10.1007/s12393-011-9036-6S10812032Abad Romero B, Bou-Maroun E, Reparet JM, Blanquet J, Cayot N (2010) Impact of lipid extraction on the dearomatisation of an Eisenia foetida protein powder. Food Chem 119:459–466Adewuyi YG (2001) Sonochemistry: environmental science and engineering applications. Ind Eng Chem Res 40:4681–4715Atchley AA, Crum LA (1988) Acoustic cavitation and bubble dynamics. 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Ultrason Sonochem 15:1075–1079Cárcel JA, Benedito J, Bon J, Mulet A (2007) High intensity ultrasound effects on meat brining. Meat Sci 76:611–619Cárcel JA, Benedito J, Rosselló C, Mulet A (2007) Influence of ultrasound intensity on mass transfer in apple immersed in a sucrose solution. J Food Eng 78:472–479Cavitus (2009) Grape colour and flavour extraction (Pat. Pend.) for red must extraction http://www.cavitus.com . Crafers. Accessed 10 Jan 2011Chea Chua S, Ping Tan C, Mirhosseini H, Ming Lai O, Long K, Sham Baharin B (2009) Optimization of ultrasound extraction condition of phospholipids from palm-pressed fiber. J Food Eng 92:403–409Chena R, Menga F, Zhang S, Liu Z (2009) Effects of ultrahigh pressure extraction conditions on yields and antioxidant activity of ginsenoside from ginseng. Sep Purif Technol 66:340–346Chivate MM, Pandit AB (1995) Quantification of cavitation intensity in fluid bulk. 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Ultrason Sonochem 1:75–79Esclapez MD, Sáez V, Milán-Yáñez D, Tudela I, Louisnard O, González-García J (2010) Sonoelectrochemical treatment of water polluted with trichloroacetic acid: from sonovoltammetry to pre-pilot plant scale. Ultrason Sonochem 17:1010–1020Ferraro V, Cruz IB, Ferreira R, Malcata JFX, Pintado ME, Castro PML (2010) Valorisation of natural extracts from marine source focused on marine by-products: review. Food Res Int 43:2221–2233Fischer CH, Hart EJ, Henglein AJ (1986) Hydrogen/deuterium isotope exchange in the hydrogen deuteride-water system under the influence of ultrasound. Phys Chem 90:3059–3060Garcia-Noguera J, Weller CL, Oliveira FIP, Rodrigues S, Fernandes FAN (2010) Dual-stage sugar substitution in strawberries with a Stevia-based sweetener. Innovative Food Sci Emerg Technol 11:225–230García-Pérez JV, Cárcel JA, de la Fuente-Blanco S, Riera-Franco de Sarabia E (2006) Ultrasonic drying of foodstuff in a fluidized bed: parametric study. Ultrasonics 44:539–543García-Pérez JV, García-Alvarado MA, Carcel JA, Mulet A (2010) Extraction kinetics modeling of antioxidants from grape stalk (Vitis vinifera var. Bobal): Influence of drying conditions. J Food Eng 101:49–58González-García J, Sáez V, Tudela I, Díez-Garcia MI, Esclapez MD, Louisnard O (2010) Sonochemical treatment of water polluted by chlorinated organocompounds. A review. Water 2:28–74Handa SS, Preet S, Khanuja S, Longo G, Rakesh DD (2008) Extraction Technologies for Medicinal and Aromatic Plants. United Nations Industrial Development Organization and the International Centre for Science and High Technology, TriesteHemwimol S, Pavasant P, Shotipruk A (2006) Ultrasound-assisted extraction of anthraquinones from roots of Morinda citrifolia. Ultrason Sonochem 13:543–548Hielscher (2011) Teltow http:// www.hielscher.com . Accessed 10 Jan 2011Hu Y, Wang T, Wang M, Han S, Wan P, Fan M (2008) Extraction of isoflavonoids from Pueraria by combining ultrasound with microwave vacuum. Chem Engin Process 47:2256–2261Ince NH, Tezcanli G, Belen RK, Apikyan PG (2001) Ultrasound as a catalyzer of aqueous reaction systems: the state of the art and environmental applications. Appl Catal B 29:167–176Jadhav D, Rekha BN, Gogate PR, Rathod VK (2009) Extraction of vanillin from vanilla pods: a comparison study of conventional soxhlet and ultrasound assisted extraction. J Food Eng 93:421–426Ji J-b, Lu X-h, Cai M-q, Xu C-c (2006) Improvement of leaching process of Geniposide with ultrasound. Ultrason Sonochem 13:455–462Kanthale PM, Gogate PR, Pandit AB, Wilhelm AM (2003) Mapping of an ultrasonic horn: link primary and secondary effects of ultrasound. Ultrason Sonochem 10:331–335Karki B, Lamsal BP, Jung S, van Leeuwen JH, Pometto AL III, Grewell D, Khanal SK (2010) Enhancing protein and sugar release from defatted soy flakes using ultrasound technology. J Food Eng 96:270–278Kardos N, Luche J-L (2001) Sonochemistry of carbohydrate compounds. Carbohydr Res 332:115–131Kotronarou A, Mills G, Hoffmann MR (1991) Ultrasonic Irradiation of para-Nitrophenol in Aqueous Solution. J Phys Chem 95:3630–3638Kuijpers MWA, Kemmere MF, Keurentjes JTF (2002) Calorimetric study of the energy efficiency for ultrasound-induced radical formation. Ultrasonics 40:675–678Leighton TG (2007) What is ultrasound? Prog Biophys Mol Biol 93:3–83Leonelli C, Mason TJ (2010) Microwave and ultrasonic processing: now a realistic option for industry. Chem Eng Process 49:885–900Li H, Pordesimo L, Weiss J (2004) High intensity ultrasound-assisted extraction of oil from soybeans. Food Res Int 37:731–738Liu J, Li J-W, Tang J (2010) Ultrasonically assisted extraction of total carbohydrates from Stevia rebaudiana Bertoni and identification of extracts. Food Bioprod Process 88:215–221Lianfu Z, Zelong L (2008) Optimization and comparison of ultrasound/microwave assisted extraction (UMAE) and ultrasonic assisted extraction (UAE) of lycopene from tomatoes. Ultrason Sonochem 15:731–737Liazid A, Schwarz M, Varela RM, Palma M, Guillén DA, Brigui J, Macías FA, Barroso CG (2010) Evaluation of various extraction techniques for obtaining bioactive extracts from pine seeds. Food Bioprod Process 88:247–252Londoño-Londoño J, Rodrigues de Lima V, Lara O, Gil A, Crecsynski Pasa TB, Arango GJ, Ramirez Pineda JR (2010) Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method. Food Chem 119:81–87Lou Z, Wang H, Zhang M, Wang Z (2010) Improved extraction of oil from chickpea under ultrasound in a dynamic system. J Food Eng 98:13–18Louisnard O, González-García J, Tudela I, Klima J, Sáez V, Vargas-Hernández Y (2009) FEM simulation of a sono-reactor accounting for vibrations of the boundaries. Ultrason Sonochem 16:250–259Luque de Castro MD, Priego-Capote F (2007) Analytical Applications of Ultrasound, Vol. 26, Techniques and Instrumentation in Analytical Chemistry. Elsevier Science, AmsterdamMa Y, Ye X, Hao Y, Xu G, Xu G, Liu D (2008) Ultrasound-assisted extraction of hesperidin from Penggan (Citrus reticulata) peel. Ultrason Sonochem 15:227–232Ma Y, Chen J-C, Liu Dong-Hong, Ye X-Q (2009) Simultaneous extraction of phenolic compounds of citrus peel extracts: effect of ultrasound. Ultrason Sonochem 16:57–62Makino K, Mossoba MM, Riesz P (1982) Chemical effects of ultrasound on aqueous solutions. Evidence for hydroxyl and hydrogen free radicals (.cntdot. OH and. cntdot. H) by spin trapping. J Chem Soc 104:3537–3539Margulis MA, Margulis IM (2003) Calorimetric method for measurement of acoustic power absorbed in a volume of liquid. Ultrason Sonochem 10:343–345Martin CJ, Law ANR (1983) Design of thermistor probes for measurement of ultrasound intensity distributions. Ultrasonics 21:85–90Mason TJ, Lorimer JP, Bates DM, Zhao Y (1994) Dosimetry in sonochemistry: the use of aqueous terephthalate ion as a fluorescence monitor. Ultrason Sonochem 1:91–95Meinhardt (2011) Leipzig. http://www.meinhardt-ultraschall.de . Accessed 10 Jan 2011Montalbo-Lomboy M, Khanal SK, van Leeuwen JH, Raman DR, Dunn L Jr, Grewell D Jr (2010) Ultrasonic pretreatment of corn slurry for saccharification: a comparison of batch and continuous Systems. Ultrason Sonochem 17:939–946Mulet A, Cárcel JA, Sanjuán N, Bon J (2003) New food drying technologies. Use of ultrasound. Food Sci Technol Int 9:215–221Naguleswaran S, Vasanthan T (2010) Dry milling of field pea (Pisum sativum L.) groats prior to wet fractionation influences the starch yield and purity. Food Chem 118:627–633Orozco-Solano M, Ruiz-Jiménez J, Luque de Castro MD (2010) Ultrasound-assisted extraction and derivatization of sterols and fatty alcohols from olive leaves and drupes prior to determination by gas chromatography–tandem mass spectrometry. J Chromatogr A 1217:1227–1235Patist A, Bates D (2008) Ultrasonic innovations in the food industry: from the laboratory to commercial production. Innovative Food Sci Emerg Technol 9:147–154Price GJ (1990) The use of ultrasound for the controlled degradation of polymer solutions. In: Mason TJ (ed) Advances in sonochemistry, vol 1. Jai Press, Cambridge, pp 231–287Riener J, Noci G, Cronin DA, Morgan DJ, Lyng JG (2010) A comparison of selected quality characteristics of yoghurts prepared from thermosonicated and conventionally heated milks. Food Chem 119:1108–1113Riera E, Golás Y, Blanco A, Gallego JA, Blasco M, Mulet A (2004) Mass transfer enhancement in supercritical fluids extraction by means of power ultrasound. Ultrason Sonochem 11:241–244Riera E, Blanco A, García J, Benedito J, Mulet A, Gallego-Juárez JA, Blasco M (2010) High-power ultrasonic system for the enhancement of mass transfer in supercritical CO2 extraction processes. Physics Procedia 3:141–146Roldán-Gutiérrez JM, Ruiz-Jiménez J, Luque de Castro MD (2008) Ultrasound-assisted dynamic extraction of valuable compounds from aromatic plants and flowers as compared with steam distillation and superheated liquid extraction. Talanta 75:1369–1375Romdhane M, Gourdon C (2002) Investigation in solid–liquid extraction: influence of ultrasound. Chem Eng J 87:11–19Rong L, Kojima Y, Koda S, Nomura H (2008) Simple quantification of ultrasonic intensity using aqueous solution of phenolphthalein. Ultrason Sonochem 8:11–15Sáez V, Frias-Ferrer A, Iniesta J, Gonzalez-Garcıa J, Aldaz A, Riera E (2005) Chacterization of a 20 kHz sonoreactor. Part I: analysis of mechanical effects by classical and numerical methods. Ultrason Sonochem 12:59–65Sáez V, Frias-Ferrer A, Iniesta J, Gonzalez-Garcıa J, Aldaz A, Riera E (2005) Characterization of a 20 kHz sonoreactor. Part II: analysis of chemical effects by classical and electrochemical methods. Ultrason Sonochem 12:67–72Sahena F, Zaidul ISM, Jinap S, Karim AA, Abbas KA, Norulaini NAN, Omar AKM (2009) Application of supercritical CO2 in lipid extraction–A review. J Food Eng 95:240–253Science Direct Database (2011) www.sciencedirect.com (Data of consulting: February 2011)Soria AC, Villamiel M (2010) Effect of ultrasound on the technological properties and bioactivity of food: a review. Trends Food Sci Technol 21:323–331Starmans DAJ, Nijhuis HH (1996) Extraction of secondary metabolites from plant material: a review. 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Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression