Manohar Lal Garg

Plant-based diets may support cognitive health through vascular, metabolic and gut-mediated pathways, with emerging biomarker and neuroimaging evidence highlighting their potential role in preventing cognitive decline and AD.

Background: Preventive strategies, including adherence to specific dietary patterns, have received increasing attention as approaches to reduce cognitive decline and dementia risk. However, findings remain inconsistent, partly due to differences in dietary assessment methods, cognitive outcomes, and THE consideration of genetic susceptibility factors such as apolipoprotein E (APOE) genotype. Methods: This study examined associations between dietary patterns and longitudinal cognitive change in 185 older adults without dementia from the Western Australia Memory Study. Participants completed a food frequency questionnaire at baseline and underwent comprehensive neuropsychological assessments at baseline and up to five follow-up visits at 18-month intervals. Composite scores were generated for six cognitive domains and the Preclinical Alzheimer’s Cognitive Composite (PACC). Results: Western and Prudent dietary pattern scores were analysed using linear mixed-effects models stratified by APOE ε4 carrier status. Among APOE ε4 carriers, greater adherence to a Western dietary pattern was associated with a faster decline in attention (p = 0.016), whereas no significant associations were observed for the Prudent dietary pattern or among APOE ε4 non-carriers. This association was attenuated after excluding participants with possible baseline cognitive impairment (MoCA < 23). Conclusion: These findings suggest that adherence to a Western dietary pattern may accelerate cognitive decline in individuals genetically at risk for Alzheimer’s disease, highlighting the importance of considering gene–diet interactions when developing dietary strategies for dementia prevention.

Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total‐tau (T‐tau) remain valuable in indicating AD‐related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non‐invasive detection and treatment approaches. This cross‐sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid‐β (Aβ) status through positron emission tomography (PET) imaging (CU Aβ− and CU Aβ+) and utilised a Biocrates‐targeted metabolomic platform and Single‐molecule array (Simoa) technology to quantify plasma levels of SMs and T‐tau, respectively. Associations between circulating SMs and T‐tau were examined within each group, with T‐tau‐associated SMs further evaluated for their association with cognitive performance and cortical Aβ burden and their potential to discriminate CU Aβ+ from CU Aβ− individuals. Significant positive correlations were observed between SMs and T‐tau levels exclusively in CU Aβ+ individuals, suggesting connections between SM‐mediated biochemical pathways and tau release from early neurodegeneration in preclinical AD. Lower SM levels were associated with weaker working memory and executive function, as well as poorer global cognition, indicating their potential predictive value for weaker cognitive performance. Moreover, SMs were also inversely associated with cortical Aβ load in CU Aβ+ individuals, possibly reflecting early SM‐mediated neuroprotective responses against AD pathogenesis. Receiver operating characteristic analysis further revealed the significant potential of the SM panel in distinguishing cortical PET‐Aβ status and enhancing the predictive performance of plasma T‐tau in CU individuals. Therefore, circulating T‐tau‐associated SMs may serve as promising early biomarkers of lipid‐mediated processes in CU older adults with cortical amyloid pathology and tau‐related neurodegeneration. image

Alzheimer’s disease (AD) is characterized by significant reductions in glucose metabolism, reflecting underlying synaptic dysfunction, correlating with cognitive decline. We aimed to explore the impact of dietary patterns on the change in glucose metabolism. Methods: This longitudinal, prospective study included 132 community-dwelling older adults without a diagnosed dementia history enrolled in the Western Australian Memory Study (WAMS). Participants completed a food frequency questionnaire at baseline and underwent [¹⁸F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at baseline and at up to two follow-up assessments scheduled approximately 18 months apart, over a maximum follow-up period of 43 months. Principal component analysis yielded two dietary patterns—named Western Diet and Prudent Diet. Linear mixed-effect models evaluated the association between dietary adherence and glucose metabolism, including potential confounders. Analysis was repeated stratified by sex. Results: Adherence to a Western Diet, characterized by high sugars and saturated fats, was associated with faster decline in glucose metabolism in the left fusiform gyrus (β = −0.00062; SE = 0.00025; FDR-adjusted p = 0.043), neocortex (β = −0.00063; SE = 0.00026; FDR-adjusted p = 0.047), left ventrolateral prefrontal (β = −0.00083; SE = 0.00032; FDR-adjusted p = 0.045 and inferior parietal region (β = −0.00344; SE = 0.00129; FDR-adjusted p = 0.033) in females. A Prudent Diet, characterized by a high intake of fruits, vegetables, and whole grains, showed no significant effects. Conclusions: Our study highlights the following: (a) The potential detrimental impact of a Western Diet on brain glucose metabolism, particularly for females, who are at higher risk for AD. The decline was observed in regions essential for cognitive functions, including visual processing and facial recognition, emphasizing the role of diet in brain health. (b) No significant associations were observed between adherence to a Prudent dietary pattern and changes in glucose metabolism.

Emerging evidence suggests altered circulating metabolite levels in individuals with Alzheimer’s disease (AD) and/or mild cognitive impairment (MCI) compared to healthy controls; how these metabolites alter with early cortical amyloidosis—before symptom onset—remains unclear. This cross-sectional study aimed to investigate plasma metabolites obtained through targeted profiling using the Biocrates AbsoluteIDQ® p400 HR kit. The study cohort comprises 100 cognitively unimpaired (CU) older adults, stratified into CU Aβ− (negative positron emission tomography [PET]-amyloid-beta [Aβ]) and CU Aβ+ (positive PET-Aβ) groups. Significantly altered metabolites were further analysed for associations across amyloid plaque deposition, cognitive performance and plasma tau phosphorylated at threonine 181 (P-tau181) levels and for their ability to differentiate cortical PET-Aβ status in CU older adults. Significant between-group differences were observed in eighteen metabolites from phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and ceramide (Cer) classes, wherein significantly lower levels of PC species and higher levels of LPC(17:1) and Cer(43:1) were detected in CU Aβ+ individuals compared to CU Aβ−. Notably, the differences became more pronounced when PC-to-LPC ratios were analysed. Across the spectrum, lower PC-to-LPC ratios were associated with greater cortical amyloid deposition, poorer cognitive performance and higher plasma P-tau181 levels. Elevated Cer(43:1) levels were also associated with higher cortical amyloid deposition. Upon receiver operating characteristic (ROC) analyses, these metabolite panels significantly distinguished CU Aβ individuals from CU Aβ−, demonstrating good to excellent diagnostic performance. Given their association with membrane damage, synaptic dysfunction, oxidative stress, neuroinflammation and apoptosis, these metabolites may represent potential biomarkers reflecting early AD-related biochemical changes in CU older adults.

GlucoTRIG is a recently developed index that incorporates postprandial insulin and triglyceride responses to quantify the potential metabolic effects of composite meals that may be associated with long-term health. The study was a randomized, controlled, crossover trial involving healthy adults (n = 12, M: 2, F: 10), aged 25.5 ± 1.6 years, with BMI 21.9 ± 0.7 kg m⁻², HbA1c 31 ± 1 mmol mol⁻¹, and fasting triglyceride (FTG) 1.2 ± 0.1 mmol L⁻¹. Three isocaloric meals (2000 kJ) were examined: reference (Ref) meal (17% protein, 26% fat, 55% carbohydrate, 0.6% fiber), high-carbohydrate, low-fat (HCLF) meal (17% protein, 13% fat, 68% carbohydrate, 0.9% fiber), and high-fat, low-carbohydrate (HFLC) meal (19% protein, 51% fat, 29% carbohydrate, 1.1% fiber). A baseline blood sample was taken followed by a further blood sample collection after the meal at 180 min. The GlucoTRIG value was calculated as [plasma triglyceride_180min (mmol L⁻¹) × plasma insulin_180min (pmol L⁻¹)] − [plasma triglyceride_0min (mmol L⁻¹) × plasma insulin_0min (pmol L⁻¹)]. Postprandial triglyceride (PPTG) changes from baseline were significantly different among the three meals: Ref (0.1 ± 0.04 mmol L⁻¹), HCLF (0.3 ± 0.1 mmol L⁻¹), and HFLC (0.6 ± 0.1 mmol L⁻¹), p < 0.001. Significant postprandial insulin (PPI) changes from baseline were also observed: Ref (13.7 ± 6.9 pmol L⁻¹), HCLF (28.9 ± 7.3 pmol L⁻¹), and HFLC (5.7 ± 4.0 pmol L⁻¹), p = 0.032. The GlucoTRIG values were: Ref (14 ± 6.5), HCLF (38 ± 7.7), and HFLC (36 ± 6.1), p < 0.001, with the Ref meal value being significantly lower than for the HCLF (p = 0.011) and the HFLC (p = 0.024) meals. The GlucoTRIG index was able to differentiate between the plasma metabolic profiles of meals with different macronutrient contents. Heightened postprandial blood levels of insulin and triglycerides may be related to long-term health outcomes.

Background: Evidence suggests that plant-based diets (PBDs) may be protective against neurodegenerative diseases such as Alzheimer's disease (AD). Objective: This study examined associations between blood-based AD biomarkers in individuals 30–75 years without current or diagnosed cardiovascular disease following different PBDs versus regular meat-eating diets (RMEs). Methods: This secondary analysis of the Plant-based Diets study measured Aβ _1–42 /Aβ _1–40 , p-tau181, NFL, and GFAP in 237 plasma samples using SIMOA from individuals following vegan, pesco-vegetarian (PVs), lacto-ovo vegetarian (LOVs), semi-vegetarian (SVs), or RME diets. Multivariable regression adjusted for age and sex. Results: Following adjustments for age and sex, plasma Aβ _1–42 /Aβ _1–40 ratio was significantly higher in PVs 0.011 (CI: 0.006, 0.016, p < 0.01), LOVs 0.011 (CI: 0.007, 0.016, p < 0.01) and SVs 0.015 (0.009–0.020, p < 0.01) groups compared to RMEs. Plasma p-tau181 was significantly higher in PVs 3.4 (CI: 0.4–6.4, p < 0.05) and LOVs 7.1 (CI: 2.5, 11.8, p < 0.01), NFL higher in PVs 5.2 (CI: 1.6, 8.7, p < 0.01) and LOVs 4.0 (CI: 1.6, 6.5, p = 0.01), and GFAP higher in PVs 26 (CI: 6, 47, p < 0.05) and LOVs 21 (5, 367, p = 0.01), all compared to RMEs. Conclusions: This analysis suggests that PBDs may be associated with blood-based AD biomarkers. Higher Aβ _1–42 /Aβ _1–40 levels in PV, LOV and SV dietary patterns compared to RMEs could indicate lesser amyloid burden, but elevated levels of other AD biomarkers in some PBDs warrant further investigation into nutrient-specific roles in AD pathology.

Background/Objectives: Despite the healthful nature of plant-based diets (PBDs) there is potential for nutritional inadequacies. This study aimed to compare dietary intakes and nutritional adequacy in Australians following PBDs compared a regular meat-eating diet. Subjects/methods: A cross-sectional study of adults (n = 240) aged 30–75 yrs, habitually following dietary patterns for ≥6 months; vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian or regular meat-eater (n = 48 per group). Dietary intakes were assessed using validated food frequency questionnaires and dietitian-administered diet histories. Multivariable regression adjusted for sex, age, BMI, race, energy intake and physical activity. Results: Compared to regular meat-eaters, vegans and lacto-ovo vegetarians had significantly lower intakes of protein (4-5 EN%), saturated fat (2-4 EN%), trans fat, cholesterol, vitamin B₁₂, iodine, riboflavin, niacin, sodium, and long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), and higher carbohydrate (5-7 EN%), fibre, vitamin E, folate, magnesium, iron, and n-6PUFA, whereas, pesco-vegetarians and semi-vegetarians had intermediate intakes. Individuals following PBDs consumed significantly more daily serves of vegetables (1–1.5 serves), fruit (1 serve, vegan only), legumes/nuts (0.5–1 serves), and less discretionary choices (0.5–1 serves) compared to regular meat-eaters. All dietary patterns were adequate in protein, exceeded in fat, inadequate in carbohydrate and met recommended serves of fruit and vegetables, but not grains. Inadequate serves were observed for meat/poultry/eggs/beans/nuts among PBDs except pesco-vegetarians, and dairy among semi-vegetarians and regular meat-eaters. Vegans and lacto-vegetarians were inadequate in vitamin B12, LCn-3PUFA, iodine, and in addition calcium among vegans, iodine in pesco-vegetarians, and LCn-3PUFA in semi-vegetarians and regular meat-eaters. Conclusion: PBDs, while higher in beneficial nutrients and wholefood groups than regular meat-eaters, may lead to nutritional inadequacies if not planned appropriately.

Background: Vegan and vegetarian dietary patterns are known to beneficially modulate risk factors for cardiovascular disease; however, the current literature does not differentiate between various plant-based diets. This study aimed to examine the association between various plant-based diets and plasma lipids and glycaemic indices compared to a regular meat-eating diet. Methods: A cross-sectional study of Australian adults (n = 230) aged 30-75yrs habitually consuming the following were recruited: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat-eater. Multivariable regression analysis was used to adjust for covariates. Results: Compared to regular meat-eaters, vegans had significantly lower total cholesterol (-0.77mmol/L,95% CI -1.15, -0.39, P < 0.001), low-density lipoprotein cholesterol (LDL-C, -0.71mmol/L, 95% CI -1.05, -0.38, P < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C, -0.75mmol/L, 95% CI -1.11, -0.39, P < 0.001), total cholesterol/HDL-C-ratio (-0.49mmol/L, 95% CI -0.87, -0.11, P = 0.012), fasting blood glucose (FBG, -0.29mmol/L, 95% CI -0.53, -0.06, P = 0.014), haemoglobin A1C (-1.85mmol/mol, 95% CI -3.00, -0.71, P = 0.002) and insulin (-1.76mU/L, 95% CI -3.26, -0.26, P = 0.021) concentrations. Semi-vegetarians had significantly lower LDL-C (-0.41mmol/L, 95% CI -0.74, -0.08, P = 0.041) and non-HDL-C (-0.40mmol/L, 95% CI -0.76, -0.05, P = 0.026) and lacto-ovo vegetarians had significantly lower FBG (-0.34mmol/L, 95% CI -0.56, -0.11, P = 0.003) compared to regular meat-eaters. There were no differences in HDL-C and triglycerides between plant-based and regular-meat diets. Conclusions: Plasma lipaemic and glycaemic measures as a collective were more favourable among vegans, whereas among lacto-ovo vegetarians and semi-vegetarians, only some measures were favourable. Trial registration: ACTRN12621000743864. Date 6/11/2021.