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Metabolic Syndrome, Cognitive Impairment and the Role of Diet: A Narrative Review.
Kouvari, M, D'Cunha, NM, Travica, N, Sergi, D, Zec, M, Marx, W, Naumovski, N
Nutrients. 2022;(2)
Abstract
BACKGROUND This narrative review presents the association between metabolic syndrome (MetS), along with its components, and cognition-related disorders, as well as the potential reversal role of diet against cognitive impairment by modulating MetS. METHODS An electronic research in Medline (Pubmed) and Scopus was conducted. RESULTS MetS and cognitive decline share common cardiometabolic pathways as MetS components can trigger cognitive impairment. On the other side, the risk factors for both MetS and cognitive impairment can be reduced by optimizing the nutritional intake. Clinical manifestations such as dyslipidemia, hypertension, diabetes and increased central body adiposity are nutrition-related risk factors present during the prodromal period before cognitive impairment. The Mediterranean dietary pattern stands among the most discussed predominantly plant-based diets in relation to cardiometabolic disorders that may prevent dementia, Alzheimer's disease and other cognition-related disorders. In addition, accumulating evidence suggests that the consumption of specific dietary food groups as a part of the overall diet can improve cognitive outcomes, maybe due to their involvement in cardiometabolic paths. CONCLUSIONS Early MetS detection may be helpful to prevent or delay cognitive decline. Moreover, this review highlights the importance of healthy nutritional habits to reverse such conditions and the urgency of early lifestyle interventions.
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Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.
Hashimoto, M, Matsuzaki, K, Maruyama, K, Hossain, S, Sumiyoshi, E, Wakatsuki, H, Kato, S, Ohno, M, Tanabe, Y, Kuroda, Y, et al
Food & function. 2022;(5):2768-2781
Abstract
Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.
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"Real-world" eligibility for aducanumab depends on clinical setting and patients' journey.
Padovani, A, Caratozzolo, S, Rozzini, L, Pilotto, A, Benussi, A, Tedeschi, G
Journal of the American Geriatrics Society. 2022;(2):626-628
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Abstract
See related editorial by Lundebjerg et al.
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Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study.
Wu, Z, Liu, Q, Zhang, Y, Guan, X, Xiu, M, Zhang, X
The international journal of neuropsychopharmacology. 2022;(2):128-135
Abstract
OBJECTIVE Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. METHODS We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. RESULTS After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup. CONCLUSIONS Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.
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Brain functions and cognition on transient insulin deprivation in type 1 diabetes.
Creo, AL, Cortes, TM, Jo, HJ, Huebner, AR, Dasari, S, Tillema, JM, Lteif, AN, Klaus, KA, Ruegsegger, GN, Kudva, YC, et al
JCI insight. 2021;(5)
Abstract
BACKGROUNDType 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODSWe therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTSInsulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSIONTransient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATIONClinicalTrials.gov NCT03392441.FUNDINGClinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.
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Assessment of cognitive and psychomotor impairment, subjective effects, and blood THC concentrations following acute administration of oral and vaporized cannabis.
Spindle, TR, Martin, EL, Grabenauer, M, Woodward, T, Milburn, MA, Vandrey, R
Journal of psychopharmacology (Oxford, England). 2021;(7):786-803
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Abstract
BACKGROUND Cannabis legalization is expanding, but there are no established methods for detecting cannabis impairment. AIM: Characterize the acute impairing effects of oral and vaporized cannabis using various performance tests. METHODS Participants (N = 20, 10 men/10 women) who were infrequent cannabis users ingested cannabis brownies (0, 10, and 25 mg Δ-9-tetrahydrocannabinol, THC) and inhaled vaporized cannabis (0, 5, and 20 mg THC) in six double-blind outpatient sessions. Cognitive/psychomotor impairment was assessed with a battery of computerized tasks sensitive to cannabis effects, a novel test (the DRiving Under the Influence of Drugs, DRUID®), and field sobriety tests. Blood THC concentrations and subjective drug effects were evaluated. RESULTS Low oral/vaporized doses did not impair cognitive/psychomotor performance relative to placebo but produced positive subjective effects. High oral/vaporized doses impaired cognitive/psychomotor performance and increased positive and negative subjective effects. The DRUID® was the most sensitive test to cannabis impairment, as it detected significant differences between placebo and active doses within both routes of administration. Women displayed more impairment on the DRUID® than men at the high vaporized dose only. Field sobriety tests showed little sensitivity to cannabis-induced impairment. Blood THC concentrations were far lower after cannabis ingestion versus inhalation. After inhalation, blood THC concentrations typically returned to baseline well before pharmacodynamic effects subsided. CONCLUSIONS Standard approaches for identifying impairment due to cannabis exposure (i.e. blood THC and field sobriety tests) have severe limitations. There is a need to identify novel biomarkers of cannabis exposure and/or behavioral tests like the DRUID® that can reliably and accurately detect cannabis impairment at the roadside and in the workplace.
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Recruitment and Baseline Characteristics of Participants in the AgeWell.de Study-A Pragmatic Cluster-Randomized Controlled Lifestyle Trial against Cognitive Decline.
Röhr, S, Zülke, A, Luppa, M, Brettschneider, C, Weißenborn, M, Kühne, F, Zöllinger, I, Samos, FZ, Bauer, A, Döhring, J, et al
International journal of environmental research and public health. 2021;(2)
Abstract
Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences.
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Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial.
Lotan, R, Ganmore, I, Livny, A, Itzhaki, N, Waserman, M, Shelly, S, Zacharia, M, Moshier, E, Uribarri, J, Beisswenger, P, et al
Journal of Alzheimer's disease : JAD. 2021;(4):1785-1795
Abstract
BACKGROUND Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. OBJECTIVE The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). METHODS The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. RESULTS At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. CONCLUSION The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.
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Evaluation of Available Cognitive Tools Used to Measure Mild Cognitive Decline: A Scoping Review.
Chun, CT, Seward, K, Patterson, A, Melton, A, MacDonald-Wicks, L
Nutrients. 2021;(11)
Abstract
Cognitive decline is a broad syndrome ranging from non-pathological/age-associated cognitive decline to pathological dementia. Mild cognitive impairment MCI) is defined as the stage of cognition that falls between normal ageing and dementia. Studies have found that early lifestyle interventions for MCI may delay its pathological progression. Hence, this review aims to determine the most efficient cognitive tools to discriminate mild cognitive decline in its early stages. After a systematic search of five online databases, a total of 52 different cognitive tools were identified. The performance of each tool was assessed by its psychometric properties, administration time and delivery method. The Montreal Cognitive Assessment (MoCA, n = 15), the Mini-Mental State Examination (MMSE, n = 14) and the Clock Drawing Test (CDT, n = 4) were most frequently cited in the literature. The preferable tools with all-round performance are the Six-item Cognitive Impairment Test (6CIT), MoCA (with the cut-offs of ≤24/22/19/15.5), MMSE (with the cut-off of ≤26) and the Hong Kong Brief Cognitive Test (HKBC). In addition, SAGE is recommended for a self-completed survey setting whilst a 4-point CDT is quick and easy to be added into other cognitive assessments. However, most tools were affected by age and education levels. Furthermore, optimal cut-off points need to be cautiously chosen while screening for MCI among different populations.
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Greek High Phenolic Early Harvest Extra Virgin Olive Oil Reduces the Over-Excitation of Information-Flow Based on Dominant Coupling Mode (DoCM) Model in Patients with Mild Cognitive Impairment: An EEG Resting-State Validation Approach.
Dimitriadis, SI, Lyssoudis, C, Tsolaki, AC, Lazarou, E, Kozori, M, Tsolaki, M
Journal of Alzheimer's disease : JAD. 2021;(1):191-207
Abstract
BACKGROUND Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function that could positively alter brain dynamics and the mixture of within and between-frequency connectivity. OBJECTIVE The balance of cross-frequency coupling over within-frequency coupling can build a nonlinearity index (NI) that encapsulates the over-excitation of information flow between brain areas and across experimental time. The present study investigated for the very first time how the Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) intervention in people with mild cognitive impairment (MCI) could affect their spontaneous EEG dynamic connectivity. METHODS Forty-three subjects (14 in MeDi, 16 in MP-EVOO, and 13 in HP-EH-EVOO) followed an EEG resting-state recording session (eyes-open and closed) before and after the treatment. Following our dominant coupling mode model, we built a dynamic integrated dynamic functional connectivity graph that tabulates the functional strength and the dominant coupling mode model of every pair of brain areas. RESULTS Signal spectrum within 1-13 Hz and theta/beta ratio have decreased in the HP-EH-EVOO group in the eyes-open condition. The intervention improved the FIDoCM across groups and conditions but was more prominent in the HP-EH-EVOO group (p < 0.001). Finally, we revealed a significant higher post-intervention reduction of NI (ΔNITotal and α) for the HP-EH-EVOO compared to the MP-EVOO and MeDi groups (p < 0.0001). CONCLUSION Long-term intervention with HP-EH-EVOO reduced the over-excitation of information flow in spontaneous brain activity and altered the signal spectrum of EEG rhythms.