Role In Cognitive Impairment Research Articles

Impaired cognitive function in Crohn’s disease: Relationship to disease activity

Background & aimsImpaired attention and response inhibition have been reported in patients with Crohn’s disease (CD) in clinical remission. Prospective studies are needed to determine whether this is a stable feature of CD and whether a similar impairment is evident in ulcerative colitis (UC). Thus, our aims were to examine whether patients with CD and UC exhibited a persistent impairment in attentional performance, and if this impairment was related to key biological indices of relevance to cognition. MethodsA prospective observational study was conducted on fifteen patients with CD and 7 with UC in clinical remission recruited from a specialty clinic and 30 healthy matched control participants. A neuropsychological assessment was carried out at baseline (visit 1) and at a 6 month follow-up (visit 2). Plasma proinflammatory cytokines, the plasma kynurenine:tryptophan (Kyn:Trp) ratio and the salivary cortisol awakening response (CAR) were also determined at each visit. ResultsAcross visits, patients with CD exhibited impaired attentional performance (p ​= 0.023). Plasma IL-6 (P ​= ​0.001) and the Kyn:Trp ratio (P ​= ​0.03) were consistently elevated and the CAR significantly blunted (P ​< ​0.05) in patients with CD. No significant relationships were identified between any biochemical parameter and altered cognitive performance. ConclusionsImpaired cognitive function is a stable feature of patients with CD. These data suggest that even where remission has been achieved, the functional impact of an organic gastrointestinal disorder on cognition is still evident. However, it is unclear at present if physiological changes due to disease activity play a role in cognitive impairment in CD.

Lipidomics and cognitive dysfunction – A Narrative review

Abstract Background More than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction. Results Forty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies. Conclusions There is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.

Synaptic remodeling and reduced expression of the transcription factors, HES1 and HES5, in the cortex neurons of cognitively impaired hyperhomocysteinemic mice

Hyperhomocysteinemia (HHcy) is associated with cognitive impairment and neurodegenerative diseases. The synaptic ultrastructure and the expression of hairy enhancer of split (HES) genes are involved in cognitive impairment induced by HHcy, but their precise role remains unclear. The present study aimed to measure synaptic remodeling and the expression of HES1 and HES5 in the cortex neurons of mice with HHcy to clarify their role in cognitive impairment. Mild HHcy was induced in ApoE−/− mice receiving a high-methionine diet. The correct response percentage, latency, and distance traveled in the mice with HHcy decreased compared with those of non-HHcy control mice (P < 0.05). There was no difference in the neuronal counts and the mean optical density of Nissl bodies in the frontal cortex of HHcy and non-HHcy mice. Increased apoptosis rates and numbers of autophagosomes were observed in the HHcy mice by TUNEL staining and electron microscopy, respectively, compared to those in the control group (P < 0.05). There was a significant increase in the area of postsynaptic density and size variation of synaptic vesicles in the HHcy group compared to that in the control (P < 0.05). Decreased expression of HES1 and HES5 was observed by western blotting and immunostaining in the HHcy group compared to that in the control (P < 0.05). Collectively, these results suggest that increased autophagy, apoptosis, synaptic remodeling, and downregulation of hes1 and hes5 are involved in the cognitive impairment induced by hyperhomocysteinemia.

Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease

ObjectivesCholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. MethodsWe included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. ResultsCompared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). ConclusionsAtrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.

The Association of Post-Stroke Cognitive Impairment and Gut Microbiota and its Corresponding Metabolites.

Post-stroke cognitive impairment (PSCI) is an important factor causing disabilities after acute ischemic stroke (AIS). Emerging evidence suggested that gut microbiota play an important role in cognitive impairment. This study aimed to explore the association between PSCI and gut microbiota. 65 patients with newly diagnostic AIS finished the fecal collection on admission and cognitive assessment 3 months later in the clinic. Fecal samples were subjected to 16SrRNA gene sequencing and gas chromatography-mass spectrometry analysis. Additionally, we enrolled new 18 AIS patients, whose treatment was supplemented by probiotics, to assess the potential of microbial treatment in PSCI. PSCI patients were characterized by the significantly decreased alpha-diversity, disturbed microbial composition, and corresponding metabolites compared with non-PSCI patients. Increased Fusobacterium and deficiency of microbial metabolized short-chain fatty acids (SCFAs) were significantly associated with PSCI. A model based on gut microbiota and SCFAs could predict 3 months or longer PSCI early and accurately after stroke onset. While traditional probiotic administration had little effect on PSCI, it could ameliorate patients' mood, including depression and anxiety in the 3 months after stroke. Our study revealed the association between PSCI and gut microbiota and its corresponding metabolites for the first time, suggesting the potential for applying microbiota and its corresponding metabolites to early clinical diagnosis and treatment of PSCI.

Interethnic differences in neuroimaging markers and cognition in Asians, a population-based study

We examined interethnic differences in the prevalence of neuroimaging markers of cerebrovascular and neurodegenerative disease in 3 major Asian ethnicities (Chinese, Malays, and Indians), as well as their role in cognitive impairment. 3T MRI brain scans were acquired from 792 subjects (mean age: 70.0 ± 6.5years, 52.1% women) in the multi-ethnic Epidemiology of Dementia In Singapore study. Markers of cerebrovascular disease and neurodegeneration were identified. Cognitive performance was evaluated using Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological assessment. Compared to Chinese, Malays had a higher burden of intracranial stenosis (OR: 2.28. 95%CI: 1.23–4.20) and cortical atrophy (β: −0.60. 95%CI: −0.78, −0.41), while Indians had a higher burden of subcortical atrophy (β: −0.23. 95%CI: −0.40, −0.06). Moreover, Malay and Indian ethnicities were likely to be cognitively impaired (OR for Malays: 3.79. 95%CI: 2.29–6.26; OR for Indians: 2.87. 95%CI: 1.74–4.74) and showed worse performance in global cognition (β for Malays: −0.51. 95%CI: −0.66, −0.37; and Indians: −0.32. 95%CI: −0.47, −0.17). A higher burden of cerebrovascular and neurodegenerative markers were found in Malays and Indians when compared to Chinese. Further research is required to fully elucidate the factors and pathways that contribute to these observed differences.

Cerebrovascular function during cognition in Parkinson's disease: A functional transcranial Doppler sonography study

Objective: Recent evidence has linked cerebrovascular abnormalities with Parkinson's Disease (PD), which may provide a new neurophysiological understanding of cognitive impairment in PD. The current study aimed to compare cerebrovascular functioning, during a cognitive task and at rest, in those with and without PD.Methods: Idiopathic PD patients (n = 30) and age- and gender-matched healthy controls (n = 30) undertook cognitive testing and completed a word generation task while blood flow velocity was monitored bilaterally with functional transcranial Doppler sonography (fTCD) of the middle cerebral arteries. The lateralisation index and its standard deviation and timing, along with the maximum peak velocity for the left and right hemispheres and their latencies and standard deviations, were calculated for each participant.Results: The PD patients showed significantly more variability of the lateralisation index compared to the control group; but there were no differences in the lateralisation index itself nor in the peak velocities. In the PD group, the variability in the peak velocities showed significant positive correlations with performance on executive function tests.Conclusion: Normal ageing has been associated with a reduction in the lateralisation index, but no alterations in the standard deviation, suggesting that cerebrovascular functional changes associated with PD differ from those of typical ageing. The within-subject variability observed in the PD group indicate abnormalities within the neurovascular coupling response. Further, the association between the within-subject variability and executive functioning in the PD group, suggests that cerebrovascular dysfunction plays an important role in cognitive impairment in PD.

The role of cognitive impairment in pain care in the emergency department for patients from residential aged care facilities: a retrospective, case-control study

BackgroundPatients with cognitive impairment are at risk of substantial delays to analgesic medication when presenting to the emergency department in pain. AimTo identify if patients from residential aged care facilities with cognitive impairment experience the same delays to analgesic medication are reported in the general emergency department population. MethodsThis study is a retrospective case-control review of patients presenting to one emergency department with pain as a presenting complaint from residential aged care, with and without cognitive impairment. ResultsPatients without cognitive impairment experience delays in time to first analgesic medication (175min vs 98min, p=0.006) compared to cognitively impaired patients from residential aged care facilities. Both cohorts of patients waited more than three times the national benchmark for analgesic medication and 66% of all patients in this study did not have pain assessment completed. ConclusionPatients presenting from residential caged care facilities in this study without cogitative impairment wait longer for analgesia then patients who present with cogitative impairment, contrary to previously described relationships. Pain assessment and treatment are open to cogitative bias, and in the absence of pain assessment cogitative bias may prevail leading to poor pain care and discrepancies between patients with and without cogitative impairment.

Association with elevated level of inflammatory biomarkers and attention deficit in Korean farmers

Inflammation plays an important role in cognitive impairments. This study examined the association of elevated biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations, with attentional deficit in Korean farmers. A total of 504 healthy Korean farmers (255 male, mean age 60 years) were enrolled from the Farmers' cohort for Agricultural work-Related Musculoskeletal disorders (FARM) study. Attention was evaluated by measuring the accuracy/error rate and speed when using a computerized Go/No-Go test. Serum level of CRP and IL-6 were measured in specimens. Higher CRP and IL-6 levels were associated with decreased accuracy rate (p < .001). The increased error rate in the Go test was related to an elevated CRP level (p < .001), while the increased error rate of the No-Go test was related to an elevated IL-6 level (p < .001). The correct response time was associated with an increased CRP level in simple and NSAID-adjusted analysis. In the age-adjusted partial correlation analysis, higher CRP and IL-6 levels were associated with a decreased accuracy rate (CRP: Partial r [pr] = −0.171, p < .001; IL-6: pr = −0.196, p < .001). The increased error rate in the Go-test was related to the elevated CRP level (pr = 0.321, p < .001), while increased error rate in the No-Go test was related to the elevated IL-6 level (pr = 0.256, p < .001). Elevated serum CRP and IL-6 were associated with attentional decline, thus suggesting the involvement of inflammation in cognitive impairments in healthy individuals.

Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention

Isoflurane and sevoflurane are both inhalation anesthetics, but in clinical application, sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity. Nevertheless, recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity, cost, and long-term anesthetic effect. Moreover, sevoflurane possibly has less cognitive impact on young mice. In this study, C57BL/6 mice aged 8-10 weeks were exposed to 1.2% isoflurane or 2.4% sevoflurane for 6 hours. Cognitive function and memory were examined in young mice using the novel object recognition, contextual fear conditioning, and cued-fear extinction tests. Western blot assay was performed to detect expression levels of D1 dopamine receptor, catechol-O-methyltransferase, phospho-glycogen synthase kinase-3β, and total glycogen synthase kinase-3β in the hippocampus. Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test. Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group. Long-term sevoflurane exposure did not affect memory consolidation, while isoflurane led to memory consolidation and reduced retention. Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3β and upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane. These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane, which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3β in the hippocampus. This study was approved by the Institutional Animal Care and Use Committee, Nanjing University, China on November 20, 2017 (approval No. 20171102).

Diffuse Tract Damage in CADASIL Is Correlated with Global Cognitive Impairment

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ­(CADASIL) is the most common familial cerebral small vessel disease caused by notch homolog protein 3 gene mutations and is strongly associated with ischemic stroke and dementia. Patients are characterized by cognitive impairment and widespread white matter (WM) lesions. However, the relationship between WM lesions and cognitive impairment is not very clear. The aim of this study was to investigate WM microstructural abnormalities by diffusion tensor imaging (DTI) and the relationship between WM alterations and cognitive impairment in patients with CADASIL. Methods: In the present study, we evaluated WM degeneration in 18 patients with CADASIL and 18 controls by fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) based on DTI. Results: Compared with healthy controls, patients with CADASIL showed extensive and significant reductions in FA and increased RD, AD, and MD. These alterations were distributed throughout the entire brain (mainly the inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and stroke scale scores. Conclusion: Patients with ­CADASIL showed widespread WM abnormalities, and WM microstructural integrity and cognitive impairment were significantly correlated. Our results indicated that damage to WM tracts plays an important role in cognitive impairment in CADASIL.

Role of cognitive impairments and decreased muscle strength in cardiovascular mortality of 55 years and older population

Aim . To assess possible associations of impaired cognitive function (CF) with muscle strength, determined using handgrip test, as well as their role in cardiovascular mortality (CVM) in a population of 55 years and older. Material and methods . This work was carried out in the framework of the prospective cohort study “Stress, aging and health”. During the study 1876 men and women aged 55 and older were examined. CF was estimated on the Mini-Mental State Examination (MMSE) scale, the decrease of CF was recorded with scores of less than 24 points (overall 30 points). Muscle strength was estimated according to handgrip test. To assess the role of muscle strength in CVM, handgrip test values, corresponding to the first quintile, were used — less than 19 kg for women, and less than 32 kg for men. Mortality was estimated on the basis of death register using standard methods. During the observation, 247 deaths from cardiovascular diseases were recorded. Results . The study included 1876 participants aged 55 years and older (48% of men and 52% of women). CF parameters according to the MMSE questionnaire were within the normal range of more than 80% of those examined. According to the results of the regression analysis, only low values of handgrip test (at the level of 1 quintile) were reliably associated with cognitive impairments (p&lt;0,05). These associations were more pronounced in women (odds ratio (OR): 3,17; 95% CI 1,31¬7,69), compared with men (OR: 2,41; 95% CI 1,05-5,54). In 55 years and older men, cognitive impairments were significantly associated with CVM (OR: 1,97; 95% CI 1,40-2,78) and reduced muscle strength (OR: 1,63; 95% CI 1,18-2,25). Among women, only reduced muscle strength significantly increased the risk of CVM (OR: 1,77; 95% CI 1,19-2,61). The simultaneous presence of these pathologies was reliably associated with CVM. Conclusion . The presented study revealed significant associations of cognitive impairments with reduced muscle strength. The presence of both pathological disorders is prognostically unfavorable for cardiovascular death in a population of 55 years and older (both among men and women). Thus, it is recommended to consider the possibility of including of muscle strength and cognitive functioning assessment in prognostic scales.

The correlation between accumulation of amyloid beta with enhanced neuroinflammation and cognitive impairment after intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is found in approximately 40% of intracerebral hemorrhages and is associated with increased mortality and poor functional outcome. Cognitive impairment is one of the complications and occurs due to various pathological changes. Amyloid beta (Aβ) accumulation and neuroinflammation, and the Alzheimer disease-like pathology, may contribute to cognitive impairment. Iron, the degradation product of hemoglobin, correlates with Aβ. In this study, the authors investigated the correlation between Aβ accumulation with enhanced neuroinflammation and cognitive impairment in a rat model of IVH. Nine male Sprague-Dawley rats underwent an intraventricular injection of autologous blood. Another 9 rats served as controls. Cognitive function was assessed by the Morris water maze and T-maze rewarded alternation tests. Biomarkers of Aβ accumulation, neuroinflammation, and c-Jun N-terminal kinase (JNK) activation were examined. Cognitive function was impaired in the autologous blood injection group compared with the control group. In the blood injection group, Aβ accumulation was observed, with a co-located correlation between iron storage protein ferritin and Aβ. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity was elevated. Microgliosis and astrogliosis were observed in hippocampal CA1, CA2, CA3, and dentate gyrus areas, with elevated proinflammatory cytokines tumor necrosis factor-α and interleukin-1. Protein levels of phosphorylated JNK were increased after blood injection. Aβ accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.

Network substrates of cognitive impairment in Alzheimer’s Disease

ObjectivesFunctional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer’s Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. MethodsEEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. ResultsSmall-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. ConclusionsTemporal lobe disconnection plays a key role in cognitive impairment in AD. SignificanceWe combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.

Differential role of interleukin-1β in neuroinflammation-induced impairment of spatial and nonspatial memory in hyperammonemic rats.

Activated microglia and increased brain IL-1β play a main role in cognitive impairment in much pathology. We studied the role of IL-1β in neuroinflammation-induced impairment of the following different types of learning and memory: novel object recognition (NOR), novel object location (NOL), spatial learning, reference memory (RM), and working memory (WM). All these processes are impaired in hyperammonemic rats. We assessed which of these types of learning and memory are restored by blocking the IL-1 receptor in vivo in hyperammonemic rats and the possible mechanisms involved. Blocking the IL-1 receptor reversed microglial activation in the hippocampus, perirhinal cortex, and prefrontal cortex but not in the postrhinal cortex. This was associated with the restoration of NOR and WM but not of tasks involving a spatial component (NOL and RM). This suggests that IL-1β would be involved in neuroinflammation-induced nonspatial memory impairment, whereas spatial memory impairment would be IL-1β-independent and would be mediated by other proinflammatory factors.-Taoro-González, L., Cabrera-Pastor, A., Sancho-Alonso, M., Arenas, Y. M., Meseguer-Estornell, F., Balzano, T., ElMlili, N., Felipo, V. Differential role of interleukin-1β in neuroinflammation-induced impairment of spatial and nonspatial memory in hyperammonemic rats.

Cognitive Impairment That Is Induced by (R)-Ketamine Is Abolished in NMDA GluN2D Receptor Subunit Knockout Mice.

Although the N-methyl-D-aspartate receptor antagonist ketamine has attracted attention because of its rapid and sustained antidepressant effects in depressed patients, its side effects have raised some concerns. Ketamine is a racemic mixture of equal amounts of the enantiomers (R)-ketamine and (S)-ketamine. The neural mechanisms that underlie the differential effects of these enantiomers remain unclear. We investigated cognitive impairment that was induced by ketamine and its enantiomers in N-methyl-D-aspartate GluN2D receptor subunit knockout (GluN2D-KO) mice. In the novel object recognition test, (RS)-ketamine and (S)-ketamine caused cognitive impairment in both wild-type and GluN2D-KO mice, whereas (R)-ketamine induced such cognitive impairment only in wild-type mice. The present results suggest that the GluN2D subunit plays an important role in cognitive impairment that is induced by (R)-ketamine, whereas this subunit does not appear to be involved in cognitive impairment that is induced by (RS)-ketamine or (S)-ketamine.

Aberrant Brain Function in Active-Stage Ulcerative Colitis Patients: A Resting-State Functional MRI Study.

Background: Patients with ulcerative colitis (UC) usually display cognitive impairments, such as memory loss, attention deficits, and declining executive functions, particularly during the active stage of the disease. However, the potential neurological mechanisms of these symptoms remain unclear.Method: Forty-one patients with mildly to moderately active UC, as well as 42 matched healthy controls, were recruited for an examination using psychological scales, cognitive function tests and resting-state functional magnetic resonance imaging (rs-fMRI). Seed points were identified via analysis of amplitude of low-frequency fluctuation (ALFF), and functional connectivity (FC) was calculated between these seed regions and other voxels in the whole brain. Correlation analyses were performed among clinical indexes, neuropsychological assessments and neuroimaging data.Result: Compared with the healthy controls, patients with UC exhibited lower ALFF values in the bilateral hippocampal/parahippocampal (HIPP/ParaHIPP) region and higher ALFF values in the left posterior cingulate cortex (PCC.L) and left middle frontal gyrus (MFG.L). With HIPP/ParaHIPP as the seed point, the strengths of the FC in the bilateral middle frontal gyri (MFG), anterior cingulate cortex (ACC), and left caudate nucleus (CAU.L) increased; using the PCC.L as the seed point, the strengths of the FC in the middle cingulate cortex (MCC) and the left angular gyrus (AUG.L) increased. These abnormal brain regions were mainly located in the limbic system. By analyzing the correlations between these brain regions and behavioral data, we observed a close correlation between decreased HIPP/ParaHIPP activity and memory loss; increased PCC activity and strength of FC with the AUG.L were related to dysfunction of executive function and attention network in patients with UC.Conclusion: Based on these results, the limbic lobe might be the core of the brain-gut axis (BGA) and play an important role in cognitive impairments, suggesting potential mechanisms for cognitive impairment in patients with UC in the active stage of the disease.

Age‐related neurovascular coupling impairment is associated with cognitive decline in healthy individuals

BackgroundIt is predicted that by the year 2030 every 5th American will be &gt;65 years of age. There is growing importance to understand age‐associated changes that lead to vascular cognitive impairment (CI) and dementia. Normal brain function is critically dependent on moment‐to‐moment adjustment of cerebral blood flow (CBF) to neuronal activity, the process also known as neurovascular coupling (NVC). It is now well established that diminished NVC, specifically in cerebral microvasculature, plays a causal role in CI in animal models of aging, however, little is known about the effects of aging on NVC responses and their role in cognitive decline in human subjects. Transcranial Doppler (TCD) ultrasound is currently employed as an important tool to measure NVC responses in larger cerebral vessels in response to cognitive stimulation in humans, however, TCD does not provide direct information about the diameter of measured cerebral vessels and it is not clear whether same changes are applicable to cerebral microcirculation. Since human retina shares similar embryologic origins with central nervous system, studying NVC responses in the retinal vessels using Dynamic Vessel Analysis (DVA) may provide another important tool to study changes in cerebral microcirculation with aging. In this study, our goal was to investigate age‐related changes of NVC responses in macro‐ and microcirculation and their association with cognitive decline.MethodsFor our study, we enrolled 23 healthy adult volunteers of 26–80 years of age (Y: n=10, &lt;40 y.o.; and A: n=12, &gt;65 y.o.). NVC responses in cerebral macrocirculation were measured using TCD in the middle cerebral artery (MCA) during cognitive stimulation with N‐back task. CBF velocity was evaluated as a percent change of the flow during 2‐back test relative to 0‐back test. DVA was performed on the right eye of each subject using a mydriatic retinal camera and change of diameter relative to baseline in the pair of retinal artery and vein was measured during and after three consecutive 20s flicker/80s recovery intervals. NVC measurements were adjusted to mean arterial pressure.ResultsIn agreement with current knowledge, we observed age‐dependent decline in cognitive performance during N‐back test (98.8±0.4% correct answers in Y vs 91.1±2.1% in A, p&lt;0.002), and our data showed that these changes were accompanied by a decrease in CBFv in large cerebral vessels such as MCA (0.84±0.11‰/mmHg in Y vs 0.41±0.13‰/mmHg in A, p= 0.02). We have also observed that aging impaired NVC responses in retinal vessels evidenced by near‐significant decrease in maximal arterial dilation (0.37±0.06‰/mmHg in Y vs 0.18±0.06‰/mmHg in A, p=0.055) and pronounced arterial constriction (0.43±0.07‰/mmHg in Y vs 0.11±0.03‰/mmHg in A, p=0.0005).SummaryOur results indicate that cognitive performance in healthy aged individuals is associated with impairment of NVC responses in cerebral macro‐ and microcirculation. DVA may be a useful tool for detailed assessment of vascular function and for early detection of individuals at risk for VCID.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P417: Association of Breast Arterial Calcification Presence and Severity with Cognitive Function: The MINERVA Study

Mammographic Breast arterial calcification (BAC) may be a novel subclinical cardiovascular disease (CVD) risk marker. Since subclinical and clinical CVD are associated with cognitive impairment, we set out to investigate whether there is a relation between BAC presence/severity and cognitive function (CF). We used data from the M ult I eth N ic study of br E ast a R terial calcium gradation and cardio VA scular disease (MINERVA), a multiethnic cohort of women aged 60-79 at baseline (10/2012 and 2/2015) who were free of symptomatic CVD, all recruited at Kaiser Permanente of Northern California. The sample available for analyses with complete data on BAC, cognitive function and covariates was 3,919 (mean ± SD age=67 ± 4, 52% white, 18% Asian, 15% African-American and 12% Latina). A BAC continuous mass score (mg) was obtained using a validated densitometry method. BAC presence was BAC score &gt; 0 mg, and severe BAC was BAC score &gt; 20 mg. CF was dichotomized as Montreal Cognitive Assessment (MoCA) score &lt; 23 (first quartile) vs ≥ 23 (quartiles 2, 3 and 4). The unadjusted (Model 1) odds ratios (OR, 95% CI; p-value) of CF &lt; 23 vs. ≥ 23 associated with BAC &gt; 0 vs. BAC=0 was 1.15 (0.98-1.35; 0.08). However, adjustment for age, race and education (Model 2) abolished this association. Further adjustment for factors independently predicting CF (Model 3, with further inclusion of diabetes, HDL-C, CES depression score, breast feeding, multiple sclerosis and osteoarthitis) did not change the association. The unadjusted (Model 1) odds ratios (OR, 95% CI; p-value) of CF &lt; 23 vs. ≥ 23 associated with BAC &gt; 20 vs. BAC≤ 20 was 1.44 (1.02-2.01; 0.04). However, adjustment for age, race and education (Model 2) abolished this association and further adjustment for factors independently predicting CF did not alter the association. In conclusion, we found a statistically significant association between severe BAC and CF, but it was explained by covariation (confounding) by age, race and education, arguing that BAC may not play a role in cognitive impairment.

Cognitive Impairment and Memory Loss in Diabetes: A Myth or Reality

Diabetes itself might not be a risk factor but mismanagement and poor control of disease may lead to the problem. High blood glucose levels, elevated blood pressure, obesity and high cholesterol collectively lead to complications including decline in cognitive ability. The present study was designed to explore the factors effecting cognitive impairment and memory loss among diabetes patients in twin cities of Pakistan. A descriptive cross-sectional study design was used. A pre-validated data collection tool i.e. Mini Mental State Examination (MMSE) questionnaire, which is a practical method for grading the cognitive state of patients was distributed to a sample of 386 diabetes patients. After data collection the data was cleaned, coded and statistically analyzed using SPSS version 21. Out of 386 respondents 97.75% (n=377) had normal cognition level, 2.3% (n=9) had mild decline in cognition level while none of the respondents had moderate or severe cognitive impairment. Significant association for cognitive impairment and demographic variables such as gender (p = 0.006) was observed. However, no significant association for cognitive impairment was observed for age, qualification, duration and type of disease, class of medication, income level, control of disease and medication adherence. The present study concluded that majority of the diabetes patients did not show cognitive impairment and memory loss. However, mild cognitive decline was observed among males, elderly and more common in type II diabetes patients. Better qualification and income can improve knowledge, adherence and disease appraisal resulting in better approach towards management of disease. This in turn can positively affect cognition and memory loss. Thus, it can be assumed that diabetes might not directly play major role in cognitive impairment and memory loss but its poor management may affect psychomotor functions of the patients. <strong>Key words:</strong> Cognitive impairment, Memory loss, Diabetes, Pakistan.