Nutritional status is associated with the degree of cognitive impairment and depressive symptoms in a Greek elderly population.

Introduction: Cognitive impairment and malnutrition are two important public health issues in the elderly, which have been associated with their mental health.Aims: This study aims to evaluate the nutritional status of an elderly population in Greece, and its association with the grade of cognitive decline, anthropometric measures and psychological status.Materials and Methods: A total of 2092 elderly men and women were enrolled from seven Greek cities. Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) questionnaires were used to assess the impact of nutritional status on cognitive abilities and psychological status of the participants.Results: Of the elderly, 35.0% were at risk of malnutrition and 11.3% were malnourished, while 34.4% of the participants had impaired cognitive function, and 32.3% showed depressive symptoms. Malnutrition was more frequently observed in participants presenting cognitive impairment, and depressive symptoms. In multiple regression analysis, nutritional status was independently associated with cognitive and psychological status.Conclusions: A high prevalence of malnutrition was recorded in this elderly population sample, which was directly associated with cognitive impairment and depression. Diagnostic tools such as MNA, MMSE, and GDS are strongly recommended to be applied as a routine clinical practice in the elderly to timely and effectively address these health problems.

The relationship between adiposity and cognitive function in a large community-dwelling population: data from the Trinity Ulster Department of Agriculture (TUDA) ageing cohort study.

Previous reports investigating adiposity and cognitive function in the population allude to a negative association, although the relationship in older adults is unclear. The aim of this study was to investigate the association of adiposity (BMI and waist:hip ratio (WHR)) with cognitive function in community-dwelling older adults (≥60 years). Participants included 5186 adults from the Trinity Ulster Department of Agriculture ageing cohort study. Neuropsychological assessment measures included the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multi-variable linear regression models were used to assess the association between adiposity and cognitive function adjusting for insulin resistance, inflammation and cerebrovascular disease. The mean ages were 80·3 (sd 6·7), 71·0 (sd 7·3) and 70·2 (sd 6·3) years on the cognitive, bone and hypertensive cohorts, respectively. In the cognitive cohort, BMI was positively associated with immediate and delay memory, visuospatial/constructional ability, language and MMSE, and negatively with FAB (log-transformed), whereas WHR was negatively associated with attention. In the bone cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with visuospatial/constructional ability, attention and MMSE. In the hypertensive cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with immediate and delayed memory, visuospatial/constructional ability, language and MMSE and positively with FAB (log-transformed). In the cognitive and bone cohorts, the association of WHR and attention disappeared by further controlling for C-reactive protein and HbA1C. In this study of older adults, central adiposity was a stronger predictor of poor cognitive performance than BMI. Older adults could benefit from targeted public health strategies aimed at reducing obesity and obeseogenic risk factors to avoid/prevent/slow cognitive dysfunction.

Effect of dietary interventions in mild cognitive impairment: a systematic review.

Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.

Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials.

Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults. The aim of this systematic review was to determine the evidence for these claims from the scientific literature in randomised, double-blinded, controlled trials (duration: ≥1 year; participants: n≥100; age(mean): ≥65 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched four electronic databases (PubMed, Scopus, CINAHL and Web of Science) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016. Interventions included B-vitamins, n-3 fatty acids, antioxidant vitamins and herbs. Of the B-vitamin studies, four found benefits to cognition with supplementation. The first of these B-vitamin studies, in individuals with mild cognitive impairment (n 266; duration=2 years), included benefit to executive function (P=0·015) and improvements in the Mini-Mental State Examination (MMSE) among participants with baseline homocysteine above 11·3 µmol/l (P<0·001). In the same sample, the second study found cognitive benefits of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status. The third B-vitamin study (n 900; duration=2 years) reported improved performance in immediate (P=0·046) and delayed recall (P=0·013), whereas the fourth study (n 856; duration=2 years) reported slower rate of cognitive decline in the MMSE (P=0·05). One study investigating DHA treatment (n 402; duration=1·5 years) revealed the slower rate of cognitive change in apoE e4 non-carriers (P=0·03). As only five included studies revealed notable benefits, presently based on the specific compounds explored here, there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly. Future long-term trials of nutraceuticals should investigate interactions with lifestyle, blood biomarkers and genetic risk factors.

Development of functional agricultural products utilizing the new health claim labeling system in Japan.

In April 2015, Consumer Affairs Agency of Japan launched a new food labeling system known as "Foods with Function Claims (FFC)." Under this system, the food industry independently evaluates scientific evidence on foods and describes their functional properties. As of May 23, 2017, 1023 FFC containing 8 fresh foods have been launched. Meanwhile, to clarify the health-promoting effects of agricultural products, National Agriculture and Food Research Organization (NARO) implemented the "Research Project on Development of Agricultural Products" and demonstrated the risk reduction of osteoporosis of ß-cryptoxanthin rich Satsuma mandarins and the anti-allergic effect of the O-methylated catechin rich tea cultivar Benifuuki. These foods were subsequently released as FFC. Moreover, NARO elucidated the health-promoting effects of various functional agricultural products (ß-glucan rich barley, ß-conglycinin rich soybean, quercetin rich onion, etc.) and a healthy boxed lunch. This review focuses on new food labeling system or research examining functional aspects of agricultural products.

Sugar-sweetened soft drinks are associated with poorer cognitive function in individuals with type 2 diabetes: the Maine-Syracuse Longitudinal Study.

The importance of adequate nutrition on cognitive performance is well recognised. Greater intakes of soft drinks are associated with a higher risk for type 2 diabetes, as well as other cardiometabolic diseases. A few studies have specifically examined whether the intake of soft drinks may be related to cognitive function. The aim of this study was to investigate whether soft drink intakes, including both sugar-sweetened and diet beverages, are associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors, and stratified according to type 2 diabetes status. Cross-sectional analyses were undertaken using 803 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study. Cognitive function was measured using an extensive battery of neuropsychological tests. Usual dietary intake of soft drinks was assessed using a FFQ. Stratification by type 2 diabetes indicated that a greater intake of sugar-sweetened soft drinks was significantly associated with poorer performance in visual spatial memory, working memory, scanning and tracking, executive function, the global composite and the Mini-Mental State Examination in diabetic individuals. These relations were not attenuated with statistical control for BMI and other cardiovascular, lifestyle and dietary factors. Diet soft drink intake was unrelated to cognitive performance. Frequent sugar-sweetened soft drink intake was associated with poorer cognitive performance, particularly in individuals with type 2 diabetes, but the underlying causal mechanisms are yet to be determined. Longitudinal studies are needed to clarify these findings and the underlying causal mechanisms.

The role of nutrition on cognition and brain health in ageing: a targeted approach.

Animal experiments and cross-sectional or prospective longitudinal research in human subjects suggest a role for nutrition in cognitive ageing. However, data from randomised controlled trials (RCT) that seek causal evidence for the impact of nutrients on cognitive ageing in humans often produce null results. Given that RCT test hypotheses in a rigorous fashion, one conclusion could be that the positive effects of nutrition on the aged brain observed in other study designs are spurious. On the other hand, it may be that the design of many clinical trials conducted thus far has been less than optimal. In the present review, we offer a blueprint for a more targeted approach to the design of RCT in nutrition, cognition and brain health in ageing that focuses on three key areas. First, the role of nutrition is more suited for the maintenance of health rather than the treatment of disease. Second, given that cognitive functions and brain regions vary in their susceptibility to ageing, those that especially deteriorate in senescence should be focal points in evaluating the efficacy of an intervention. Third, the outcome measures that assess change due to nutrition, especially in the cognitive domain, should not necessarily be the same neuropsychological tests used to assess gross brain damage or major pathological conditions. By addressing these three areas, we expect that clinical trials of nutrition, cognition and brain health in ageing will align more closely with other research in this field, and aid in revealing the true nature of nutrition's impact on the aged brain.

Electroacupuncture for motor dysfunction and constipation in patients with Parkinson's disease: a randomised controlled multi-centre trial.

Background: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. Methods: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. Findings: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of -9.1 points (95% CI, -11.8 to -6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR -26.0 to 0.0) in the EA group and 2.5 points (IQR: -11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. Interpretation: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Funding: Shanghai "Science and Technology Innovation Action Plan" Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).

Association between C-reactive protein-albumin ratio and overall survival in Parkinson's disease using publicly available data: A retrospective cohort study.

Background: At present, many studies have confirmed that inflammation plays a central role in Parkinson's disease (PD). The inflammatory index is related to the prognosis of the disease, but a single inflammatory index has some limitations. The C-reactive protein-albumin ratio (CAR) is a better marker of inflammation or nutritional status than C-reactive protein (CRP) or albumin (Alb), but there is limited study on the association between CAR and the overall survival (OS) of PD. Object: To study the association between CAR and OS in PD patients. Methods: All of these data were obtained from the Dryad Digital Repository, based on which we conducted a secondary analysis. The study was conducted by the Department of Neurology, the National Regional Center for Neurological Disorders, and the National Hospital of Utano study between March 2004 to November 2007. The final analytic sample included 235 PD patients with the outcome of survival or all-cause death from the study registration to the endpoint. In this study, univariate and multivariate COX regression analyses were used to calculate the adjusted hazard ratio (HR), with a 95% confidence interval (CI). In addition, the association between CAR and OS in PD patients was explored by Kaplan-Meier curve and subgroup analysis. Results: This study included 235 PD patients with an average age of 62.25 years, including 135 females and 100 males, and 45 died during the follow-up period. CAR was associated with gender, modified Hoehn-Yahr stages (mH-Y), and Mini-Mental State Examination (MMSE) of PD patients. In the COX multivariate regression model, after adjusting the age, gender, PD duration, mH-Y, MMSE, and the non-steroidal anti-inflammatory drugs, CAR was found to be associated with the OS in PD (HR = 1.54, 95% CI = 1.01-2.34, p = 0.044). Subgroup analysis showed that the subgroup did not play an interactive role in the association between the prognosis of patients with CAR and PD (p for interaction >0.05), and the results remained stable. Conclusions: The all-cause mortality of PD patients with a high level of CAR is higher, which indicates that the poor overall survival of PD patients is associated with the increase of CAR. The CAR may be a reliable prognostic biomarker for PD patients.

Optical Coherence Tomography Assessment of Macular Thickness in Alzheimer's Dementia with Different Neuropsychological Severities.

This retrospective case-control study aimed to investigate associations between disease severity of Alzheimer's dementia (AD) and macular thickness. Data of patients with AD who were under medication (n = 192) between 2013 and 2020, as well as an age- and sex-matched control group (n = 200) with normal cognitive function, were included. AD patients were divided into subgroups according to scores of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Macular thickness was analyzed via the Early Treatment Diabetic Retinopathy Study (ETDRS) grid map. AD patients had significant reductions in full macula layers, including inner circle, outer inferior area, and outer nasal area of the macula. Similar retinal thinning was noted in ganglion cells and inner plexiform layers. Advanced AD patients (MMSE score < 18 or CDR ≥ 1) showed more advanced reduction of macular thickness than the AD group (CDR = 0.5 or MMSE ≥ 18), indicating that severe cognitive impairment was associated with thinner macular thickness. Advanced AD is associated with significant macula thinning in full retina and inner plexiform layers, especially at the inner circle of the macula. Macular thickness may be a useful biomarker of AD disease severity. Retinal imaging may be a non-invasive, low-cost surrogate for AD.

Decreased circulating branched-chain amino acids are associated with development of Alzheimer's disease in elderly individuals with mild cognitive impairment.

Background: Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants. Method: In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," N = 87) and converted to Alzheimer's disease (AD) ("AD-convert," N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted. Results: Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group. Conclusion: The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status. Clinical trial registration: [https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Zonisamide improves axial symptoms in dementia with Lewy bodies with parkinsonism: Post hoc analysis of clinical trials.

Patients with dementia with Lewy bodies (DLB) experience worsening axial symptoms with disease progression, which can negatively affect quality of life. Previous phase 2 and 3 clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with DLB. In the present study, we performed a post hoc analysis of pooled data from the previous phase 2 and 3 trials to examine the effect of zonisamide on axial symptoms in this patient group. In our pooled analysis, the primary outcome was the change from baseline to 12 weeks in axial symptom score, measured as the sum of Unified Parkinson's Disease Rating Scale Part III items relevant to gait/balance/midline function. A total of 498 patients were included in this analysis. Zonisamide 25 mg and 50 mg significantly reduced the axial symptom score at week 12 compared with placebo (p < 0.01 and p < 0.001, respectively, by mixed model of repeated measures). Our findings indicate that zonisamide may improve axial symptoms in DLB with parkinsonism and, thus, may potentially reduce the risk of falls and improve quality of life in this vulnerable patient population.

Ten-Second Tandem Stance Test: A Potential Tool to Assist Walking Aid Prescription and Falls Risk in Balance Impaired Individuals.

Objective: To assess the utility of a 10-second tandem stance test in predicting gait impairment and the need for a mobility aid. Design: Cross-sectional study. Setting: Public hospital ambulatory and hospitalized care. Participants: Participants were drawn from referrals to the physiotherapy service and patients identified by health care staff as needing mobility assessment. Eighty-seven people were referred to the study. Sixty-one individuals (N=61) consented to participate; mean age was 76±9.8 years and 61% were female. All participants were community dwelling. Intervention: The 10-second tandem stance test and gait parameters were measured while walking with no walking aid, a walking stick, and a 4-wheeled walker were assessed. Main Outcome Measures: Associations between the 10-second tandem stance test performance with prescribed walking aids (primary outcome variable), gait parameters (gait cycle time, cadence, stance phase, swing phase, double support, stride length, speed, peak angle velocity, maximal heel clearance), falls history, falls risk (Falls Risk for Older People in the Community [FROP-Com]), and walking aid use. Results: Inability to maintain tandem stance for 10 seconds significantly increased the odds of requiring a prescribed walking aid (odds ratio [OR], 5.19; P=.01). Tandem stance test time was positively correlated with stride length, gait speed, peak angle velocity, and maximal heel clearance during the gait cycle. Correlation between tandem stance time and number of falls was weak but significant (ρ=-0.31, P=.01), and FROP-Com score for falls risk was negative and moderate for nonpreferred foot behind (ρ=-0.58, P<.01). The 10-second tandem stance with nonpreferred foot behind was associated with falling in previous 12 months (P=.04). Walking aid use history in subgroups with the individuals who cannot maintain the tandem stance with nonpreferred foot behind for 10 seconds was associated with falling in previous 12 months (OR, 55.00; 95% CI, 2.44-1238.46; P=.01). Conclusions: The 10-second tandem stance test was associated with professionally prescribed walking aids, gait parameters with prescribed walking aids, falls, and walking aid use history, indicating the test may be useful to guide the prescription of walking aids.

Motor cortical plasticity and its correlation with motor symptoms in Parkinson's disease.

Background: The relationship between abnormal cortical plasticity and parkinsonian symptoms remains unclear in Parkinson's disease (PD). Objective: We studied the relationship between their symptoms and degree of Long-term potentiation (LTP)-like effects induced by quadripulse magnetic stimulation (QPS) over the primary motor cortex, which has a small inter-individual variability in humans. Methods: Participants were 16 PD patients (drug-naïve or treated with L-DOPA monotherapy) and 13 healthy controls (HC). LTP-like effects by QPS were compared between three conditions (HC､PD with or without L-DOPA). In PD, correlation analyses were performed between clinical scores (MDS-UPDRS, MMSE and MoCA-J) and the degree of LTP-like effects induced by QPS. Results: In PD, QPS-induced LTP-like effect was reduced and restored by L-DOPA. The degree of the LTP was negatively correlated with MDS-UPDRS Part I and III scores, but not with MMSE and MoCA-J. In the sub-scores, upper limb bradykinesia and rigidity showed a negative correlation with the LTP-like effect whereas the tremor had no correlation. Conclusions: Our results suggest that motor cortical plasticity relate with mechanisms underlying bradykinesia and rigidity in the upper limb muscles. LTP induced by QPS may be used as an objective marker of parkinsonian symptoms.

Improvement of memory function via a combination of exercise and soy peptide supplementation in community-dwelling older adults: A randomized controlled trial.

Background: Soy peptide, when consumed as a functional food, has been reported to improve cognitive function. This study aimed to verify the combined effect of soy peptide supplementation and exercise on cognitive function among community-dwelling older adults in Japan. Methods: In this population-based, non-blinded randomized controlled trial, 72 community-dwelling older adults who were independent in activities of daily living were randomly assigned to an "exercise plus nutrition" program (Ex + Nt group, n = 36) or an exercise program (Ex group, n = 36). For 3 months, both groups participated in an exercise and cognitive training regimen once per week, with the Ex + Nt group receiving soy supplementation once per week. Pre- and post-intervention measurements included grip strength, gait speed, skeletal muscle mass index, and scores on Addenbrooke's Cognitive Examination-Revised, trail-making test A, and the Geriatric Depression Scale. Participant enrollment for this study started in January 2019 and ended in April 2019. Results: Exercise training increased the skeletal muscle mass index by 2.0% and 3.0% in the Ex + Nt and Ex groups, respectively. The Ex + Nt group exhibited a significant 0.3-point increase in the memory score. Conclusion: A 3-month exercise program combined with soy peptide supplementation may be effective in improving both motor and memory function in community-dwelling older adults.

Retinal and Choroidal Changes in Men Compared with Women with Alzheimer's Disease: A Case-Control Study.

Purpose: To evaluate differences in the retinal microvasculature and structure and choroidal structure among men and women with Alzheimer's disease (AD) compared with age-matched cognitively normal male and female controls. Design: Case-control study of participants ≥ 50 years of age. Participants: A total of 202 eyes of 139 subjects (101 cases and 101 controls). Methods: All participants and controls underwent OCT and OCT angiography (OCTA), and parameters of subjects with AD were compared with those of cognitively normal controls. Main Outcome Measures: The foveal avascular zone (FAZ) area, vessel density (VD), and perfusion density (PD) in the superficial capillary plexus within the 3- and 6-mm circle and ring using Early Treatment Diabetic Retinopathy Study (ETDRS) grid overlay on OCTA; central subfield thickness (CST), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT. Results: No significant sex differences in VD or PD were found in the AD or control cohorts; however, there were greater differences in VD and PD among AD female participants than AD male participants compared with their respective controls. The CST and FAZ area were not different between male and female AD participants. Among controls, men had a thicker CST (P < 0.001) and smaller FAZ area (P = 0.003) compared with women. The RNFL thickness, GCIPL thickness, and CVI were similar among male and female AD participants and controls. Conclusions: There may be a loss of the physiologic sex-related differences in retinal structure and microvasculature in those with AD compared with controls. Further studies are needed to elucidate the pathophysiological basis for these findings.

Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population: The Hisayama Study.

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)-were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30-2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.

Neural synchronization analysis of electroencephalography coherence in patients with Parkinson's disease-related mild cognitive impairment.

Introduction: The underlying pathophysiology of slight cognitive dysfunction in Parkinson's disease-related mild cognitive impairment (PD-MCI) is yet to be elucidated. Our study aimed to evaluate the association between cognitive function and brain functional connectivity (FC) in patients with PD-MCI. Methods: Twenty patients with sporadic PD-MCI were evaluated for FC in the brain network. Further, electroencephalography (EEG) coherence analysis in the whole-brain and quantified regional coherence using phase coupling were performed for each frequency, and motor and cognitive function were assessed in the whole-brain. Results: The degree of cognitive impairment was related to a decrease in the coherence in the alpha ranges. The regional coherence in the left frontal-left parietal region rather than the right frontal-right parietal region showed a higher correlation with the cognitive function scores. Conclusion: The differences in EEG coherence across different types of cognitive dysfunction reflect a compensatory response to the heterogeneous and complex clinical presentation of PD-MCI. Our findings indicate decreased brain efficiency and impaired neural synchronization in PD-MCI; these results may be crucial in elucidating the pathological exacerbation of PD-MCI.

Verification of the association between cognitive decline and olfactory dysfunction using a DEmentia screening kit in subjects with Alzheimer's dementia, mild cognitive impairment, and normal cognitive function (DESK study): A multicenter, open-label, interventional study.

Background and purpose: Olfactory dysfunction may be an early symptom of degenerative neurological disorders such as mild cognitive impairment (MCI), which may progress to cognitive decline and Alzheimer's disease (AD). We investigated the relationship between cognitive decline and olfactory dysfunction in healthy controls and patients with MCI or AD using the DEmentia Screening Kit (DESK), an olfactory identification assessment tool designed for Japanese populations. Methods: In this multicenter, open-label, interventional study conducted from 16 September 2020 to 30 April 2021, participants underwent olfactory tests using the DESK tool. This included 10 odorants at two concentrations (weak/strong) including toothpaste, butter, and India ink. Results: Among 223 participants, 100, 61, and 62 were healthy controls, MCI patients, and AD patients (mean ages, 57.4, 72.8, and 76.3 years; total DESK olfaction scores, 18.4, 14.7, and 7.4), respectively. Significant differences in total olfaction scores were observed between groups (healthy controls vs MCI, healthy controls vs AD, and MCI vs AD). Significant between-group total score differences were shown for olfaction scores with both the 10 strong and 10 weak odorant varieties. Conclusion: The DESK tool may discriminate between healthy individuals and those with MCI or AD, facilitating early screening for cognitive decline among Japanese patients, although the effect of age on DESK olfaction scores has not been fully explored.

A Comparison of Different Frailty Scores and Impact of Frailty on Outcome in Patients With Cirrhosis.

Background & aims: There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. Methods: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. Results: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores. Conclusions: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.