Diagnosis Of Cognitive Decline Research Articles

A Genome-Wide Interaction Study of Erythrocyte ω-3 Polyunsaturated Fatty Acid Species and Memory in the Framingham Heart Study Offspring Cohort

BackgroundCognitive decline, and more specifically Alzheimer’s disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids. ObjectivesWe aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual’s genetically conferred risk of cognitive decline. MethodsThe Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness). ResultsOur analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits. ConclusionsIn this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

Predictive ability of the IQCODE items for detection of cognitive decline and dementia in aging adults with Down syndrome

AbstractBackgroundThere is evidence of a genetic association between Down Syndrome (DS) and early progression of Alzheimer’s disease (AD). Few brief instruments have been validated for the screening of dementia in this population. Previously, we showed that the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) may be useful for cognitive screening in adults with DS1. Nonetheless, the adaptation of certain items to account for the presence of intellectual deficiency may increase diagnostic accuracy. The aim of the present study is to evaluate the predictive ability of IQCODE items for adults with DS.MethodUnivariate and multivariate logistic regressions were used to assess the effects of the 26 IQCODE items on the diagnosis of cognitive decline (prodromal dementia or dementia versus stable cognition) according to the Cambridge Examination for Mental Disorders of Older People with DS and Others with Intellectual Disabilities, CAMDEX‐DS. The study comprised 92 participants with DS aged ≥35 years. The accuracy of the final multivariate model was evaluated using receiver operator characteristics (ROC) curve.ResultAssociations were found between all IQCODE items and diagnosis, except for two items (handling money for shopping and financial matters). Multivariate logistic regression using the CAMDEX‐DS diagnosis as dependent and the items of IQCODE as predictors, showed that four items remained in the model (remembering: members of family and friends, day and month, things they learned when they were younger, and adjusting to change in routine). Participants who presented more difficult with these items were, respectively, 84.1, 86.1, 10.1 and 23.6 times more likely to have a diagnosis of prodromal dementia or dementia. Using the estimated probability of these 4 items, we found an area under the ROC curve of 0.961.ConclusionThe IQCODE items showed good ability to discriminate subjects with cognitive decline as indicated by the CAMDEX‐DS. The use of 4 of the IQCODE items proved to suffice to discriminate between diagnostic groups. We will next perform an adaptation and validation study to warrant the “IQCODE‐DS” as a reliable, brief test for the cognitive screening in this population.

Net Carbohydrate Consumption is Associated with Cortical Thickness in Cognitively Impaired Older Adults with Confirmed Amyloid Burden

AbstractBackgroundA low carbohydrate diet has been suggested as a treatment for Alzheimer’s disease (AD)1,2. One of the features of AD is widespread cortical thinning3; however, no study has demonstrated that carbohydrate intake is linked to cortical thickness in patients with confirmed AD‐related neuropathology. The aim of this study is to test the hypothesis that higher carbohydrate intake is associated with thinner cortex.MethodCortical thickness was estimated from T1‐weighted MR images using FreeSurfer with an alpha of p<0.05 (vertex‐wise) and p<0.01 (cluster‐wise correction for multiple comparisons). We calculated net carbohydrate intake using a Food Frequency Questionnaire (FFQ) as input to the validated FFQ EPIC Tool for Analysis4 in 22 participants aged 57‐84 (mean = 70.1 years, SD = 6.2) with a diagnosis of mild cognitive impairment (MCI) or mild AD and confirmed amyloid burden.ResultsParticipants, on average, ate moderate to low levels of net carbohydrates (mean = 124 g, SD = 66). No participant exceeded the USDA guidelines for net average daily carbohydrate intake5. Most ate less than CDC guidelines for managing diabetes6 (N = 19). Participants were drawn from the Pacific Brain Health Center, a clinical practice centered around addressing lifestyle and located in Santa Monica, California. We found that higher net carbohydrate intake was significantly associated with thinner cortex, accounting for age, within the left middle frontal gyrus (size = 2900 mm2). Uncorrected results (cluster size>100 mm2) showed that throughout the cortex, we saw a widespread pattern of cortical thinning, including regions within the middle temporal, fusiform, lingual, supramarginal, cingulate, superior parietal, postcentral, paracentral, orbitofrontal, inferior parietal, superior frontal gyri and insula. Only one region, the postcentral gyrus, showed a positive correlation, strongly suggesting the validity of these findings.ConclusionsHigher carbohydrate intake was significantly associated with thinner cortex in this cross‐section of older adults with cognitive impairment and confirmed amyloid burden. Prior research in older adults eating a Mediterranean diet did not detect this association7. Our sample was unique in that they ate fewer carbohydrates and had a diagnosis of cognitive decline with confirmed amyloid burden. Future directions of this research will assess how longitudinal trajectories of cortical thinning are impacted by changes in net carbohydrate consumption.

What We Should Not Forget about Down Syndrome

Down syndrome is the foremost common genetic cause of intellectual disability. The additional copy of chromosome 21 confers potential changes in virtually all organ systems, including the brain, neck structures, and spine. Neuroradiologists should be aware of the multitude of imaging findings in patients with Down syndrome to correctly identify and diagnose life-altering conditions associated with this syndrome. In particular, the high prevalence of age-related cognitive decline and dementia stands out more clearly in recent decades due to the notable increase in these individuals' survival. Although the early and timely diagnosis of cognitive decline in patients with varying degrees of intellectual disability has not been an easy task from the clinical point of view, anatomic and functional brain studies have shown an essential role because they allow the early recognition of abnormalities that precede the cognitive decline. Furthermore, the similarities and differences in neuropathologic, genetic, and imaging aspects in patients with Down syndrome have allowed extrapolation for a better understanding of the mechanisms linked to Alzheimer disease development.Learning Objective: To review and systematize the distinctive characteristics and abnormalities of the head and neck, vertebral column, and CNS present in Down syndrome

Diagnosis of cognitive decline and dementia in rural areas - A scoping review.

Due to the demographic change, the global prevalence of dementia will continually rise. Barriers to diagnosis and care are still high. But timely diagnosis is associated with valuable benefits and can promote timely and optimal management. Receiving an early diagnosis is especially in rural areas a problem due to the limited access to assessments. Therefore, the aim of our scoping review is to investigate different interventions targeted at rural living elderly to screen and diagnose cognitive decline and dementia. A scoping review was conducted in line with the framework of Arksey and O'Malley. The following databases were systematically searched: PubMed, PsycINFO, Cochrane Library, and ScienceDirect. The interventions were categorized in four main categories (interventions for general practitioners/institutions; online/mobile offers; telehealth applications; telephone-based screenings). Thirty studies were included. The four categories show different scopes of application. Telehealth applications show that it is feasible and valid to diagnose dementia via videoconference. Assessments described in three other categories show that remotely used tools are appropriate to screen for mild cognitive impairment or cognitive decline, but are not valid to establish a dementia diagnosis. Telehealth applications can appropriately be used to diagnose dementia. However, most of the studies included only small sample sizes and did not test the applications explicitly in rural or remote populations. Therefore, studies taking these limitations into account are needed. On top, only two RCTs are included in this review indicating that more high quality studies in this field are needed.

PP.03.17] HYPERTENSION AND COGNITIVE FUNCTION IN THE ELDERLY

Objective: Hypertension is very common in older patients and is considered to be a risk factor for cognitive decline; the 2013 ESH/ESC Guidelines for the management of arterial hypertension suggest the use of cognitive evaluation tests in the clinical assessment of elderly hypertensive patients. Nonetheless, there is still controversy over which screening test is more appropriate and cognitive impairment is usually under-diagnosed in these patients. Our study evaluates the application of a first-line screening to assess cognitive function in old hypertensive patients without a previous diagnosis of cognitive impairment. Design and method: in this observational study we enrolled 80 consecutive hypertensive patients referred to our Centre for Hypertension in the Elderly and aged 65 years or older. All patients underwent a first-line cognitive evaluation with the Mini-Cog test, including three-item repetition and recall and clock drawing. If the Mini-Cog was suggestive for cognitive impairment, the patient was further evaluated with the Mini Mental State Examination (MMSE); in case of a MMSE score inferior to 28, a Neuropsychological Evaluation (NPE) was performed. Results: the mean age of our population was 75.7 ± 5.5 (range 66–90); the 27.5% was octogenarian. The mean number of drugs of patients’ daily therapy was 6.5 ± 2.8, including 2.8 ± 1.2 anti-hypertensive drugs. For what concerns blood pressure (BP) control, all patients had both clinic and out-of-office BP values in the target range. Mean systolic and diastolic BP values were similar in patients with normal and abnormal Mini-Cog Test results. A Mini-Cog Test suggestive for cognitive impairment was observed in the 20% of our study population (16/80); 5 of these patients had a MMSE score inferior to 28. After the NPE, a diagnosis of cognitive decline was confirmed in 2 patients (2.5% of the population). The 39.1% of patients with a normal Mini-Cog Test performed an abnormal Clock Drawing Test (CDT), therefore the 51.3% of our study population had a deficit in clock drawing. Conclusions: According to our results, the Mini-Cog cannot be suggested as a screening test for the evaluation of cognitive function in old hypertensive patients.

A review article in Cognitive deficits in Parkinson’s Disease

Parkinson’s disease (PD) is a common, progressive, disabling, neurodegenerative disorder, that apart from well known motor symptoms, reveals a wide spectrum of non-motor features, that are now widely accepted as part of the clinical aspect, and cognitive decline is a very important part of these non motor presentations. The diagnosis of cognitive decline in PD can be extremely challenging, remaining largely based on clinical and cognitive assessments. Expert work groups have issued diagnostic criteria and methods for PD dementia and cognitive impairement. This manuscript has gathered relevant data in order to obtain an updated review regarding cognitive deficit in PD, from mild stages to dementia. This article has summarized clinical features, diagnostic methods, and therapeutic issues of cognitive decline in PD.

Factors Associated with Brain Atrophy Estimated with Automatic Voxel- Based Morphometry of Structural Magnetic Resonance Images in Elderly Diabetic Patients: Impact of Albuminuria on Hippocampal Atrophy

Background: We investigated what factors were associated with brain atrophy in elderly patients with type 2 diabetes. Methods: We evaluated hippocampal and whole brain atrophy with automatic voxel-based morphometry of structural magnetic resonance image (MRI), voxel-based specific analysis regional analysis for Alzheimer’s disease (VSRAD), in 70 diabetic subjects and 35 non-diabetic subjects. Cognitive function tests – MMSE, word recall (immediate and delayed), Digit Symbol Substitution test (DSST), and Stroop Color Word (Stroop) test were performed. Cerebral small vessel disease (SVD) was diagnosed as silent brain infarct and white matter lesions (WMLs) according to MRI. Results: Significantly stronger hippocampal and whole brain atrophy were observed in diabetic patients than non-diabetic subjects. The levels of glycosylated hemoglobin A1c were significantly correlated with indices of hippocampal and whole brain atrophy. In diabetic subjects, hippocampal atrophy was independently associated with age, albuminuria, serum intercellular adhesion molecules -1 levels and lower diastolic blood pressure, while whole brain atrophy was associated with age and subcortical WMLs grade. Regarding an association between albuminuria and brain atrophy, significant hippocampal and whole brain atrophy were found in patients with albuminuria after adjusting for confounders. Hippocampal atrophy was independently associated with word recall and Stroop test after adjustment, while whole brain atrophy was also associated with word recall, DSST, and Stroop test, although the association weakened after adding degree of SVD to the variables. Conclusions: Albuminuria was an independent risk factor for brain atrophy, especially hippocampal atrophy, which was associated with cognitive impairment, suggesting that the management of albuminuria may prevent progression of brain atrophy resulting in cognitive decline. In addition, the usefulness of VSRAD to support diagnosis of cognitive decline associated with brain atrophy was shown in daily clinical setting.

Clinical workout for the early detection of cognitive decline and dementia.

Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases (PDs) and prion disorders, all of which stem from toxic protein aggregation. All of these diseases are correlated with cognitive decline. Cognitive Decline is a dynamic state from normal cognition of aging to dementia. According to the original criteria for Alzheimer's Disease (AD) (1984), a clinical diagnosis was possible only when someone was already demented. The prevalence rates of Cognitive Decline (mild cognitive impairment plus dementia) are very high now and will be higher in future because of the increasing survival time of people. Many neurological and psychiatric diseases are correlated with cognitive decline. Diagnosis of cognitive decline is mostly clinical (clinical criteria), but there are multiple biomarkers that could help us mostly in research programs such as short or long, paper and pencil or computerized neuropsychological batteries for cognition, activities of daily living and behavior, electroencephalograph, event-related potentials, and imaging-structural magnetic resonance imaging (MRI) and functional (fMRI, Pittsburgh bound positron emission tomography, FDG-PET, single photon emission computerized tomography and imaging of tau pathology)-cerebrospinal fluid proteins (Abeta, tau and phospho-tau in AD and α-synuclein (αSyn) for PD). Blood biomarkers need more studies to confirm their usefulness. Genetic markers are also studied but until now are not used in clinical praxis. Finally, in everyday clinical praxis and in research workout for early detection of cognitive decline, the combination of biomarkers is useful.

Cognitive alterations in chronic kidney disease: an update.

Impairment of cognitive functions occurs frequently in chronic kidney disease (CKD). The conditions most associated with this decline are depression, delirium, mild cognitive impairment and dementia. The mechanisms involved have not been established yet, but some factors, as neuronal damage by uremic toxins, cerebrovascular ischemic lesions, oxidative stress, chronic inflammation, anemia, hyperhomocysteinemia, the endothelial dysfunction may play a critical role. The neuropsychological performance improves with the initiation of dialysis, although some cognitive dysfunctions remain even after treatment, especially in the areas of attention, cognitive flexibility, memory and learning. Kidney transplantation may improve and even reverse some cognitive deficits detected in the dialysis period, despite some compromise in verbal memory and executive functions remain after transplantation. The diagnosis of cognitive decline in patients with CKD may have an important impact on the management and prognosis. This paper presents an update on the decline of cognitive function in patients with CKD.

Abstract 2640: Montreal Cognitive Assessment as a Short and Valuable Cognitive Evaluation in Acute Stroke

Background: Stroke patients are at high risk of developing dementia, but no agreement exists on what instrument should be used in the acute stroke phase to detect patients at higher risk of cognitive decline. Our aims were to investigate: 1) the feasibility and applicability of the Montreal Cognitive Assessment (MoCA) test in the acute phase of stroke; 2) the predictive value of MoCA on the diagnosis of cognitive impairment. Methods: Consecutive stroke patients (ischemic or hemorrhagic) admitted to our Stroke Unit were evaluated with MoCA between 5-9 days after stroke. Pre-morbid functional and cognitive status were assessed by a structured interview to caregivers. Neuroimaging information was collected regarding index and pre-existing lesions (number and site of lesions, leukoaraiosis, atrophy). Clinical and neuropsychological follow-up was scheduled after 6 months. Results: From December 2009 to December 2010, out of 208 patients with stroke, 138 (66%) were enrolled [mean age 69.1+/-15.0; males 62%; mean NIHSS score 5.7+/-7.7]. Non-enrolment was mostly due to unfitting of the time window inclusion criteria. MoCA was applicable to 114/138 (83%) of enrolled patients and the mean score was 17.9+/-7.2. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR(95% CI)=1.4(1.2-1.7) for each point] and left sided lesions [OR(95% CI)=13.3(1.8-97.9)]. After 6 months, 73 patients (53%) have been re-assessed: 40 had cognitive impairment (6 dementia, 34 MCI), while the remaining 33 did not show any cognitive impairment. Using logistic regression model, considering clinical variables such as age, gender, years of schooling, NIHSS, and pre-morbid cognitive status, MoCA was the only predictor of cognitive decline [OR(95% CI)=1.4(1.2-1.6) for each test point]. When adding neuroimaging features to the model, the independent effect of MoCA was only slightly attenuated [OR(95% CI)=1.4(1.1-1.7)]. The other independent predictor of cognitive decline turned out to be leukoaraiosis severity [OR(95%CI)=0.4(0.2-0.9) for each point of the van Swieten scale]. Conclusions: Our preliminary results indicate that the MoCA is feasible and applicable in the acute phase of stroke. Moreover, MoCA seems to have a predictive effect on the diagnosis of cognitive decline at 6-month follow-up, making it a good candidate for cognitive screening in stroke setting.

Cognitive Impairment and Dementia in Parkinson’s Disease: Clinical Features, Diagnosis, and Management

Parkinson’s disease (PD) is a common, disabling, neurodegenerative disorder. In addition to classical motor symptoms, non-motor features are now widely accepted as part of the clinical picture, and cognitive decline is a very important aspect of the disease, as it brings an additional significant burden for the patient and caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive impairment (MCI) and dementia, can be extremely challenging, remaining largely based on clinical and cognitive assessments. Diagnostic criteria and methods for PD dementia and MCI have been recently issued by expert work groups. This manuscript has synthesized relevant data in order to obtain a pragmatic and updated review regarding cognitive decline in PD, from milder stages to dementia. This text will summarize clinical features, diagnostic methodology, and therapeutic issues of clinical decline in PD. Relevant clinical genetic issues, including recent advances, will also be approached.

The relationship between body mass index and incidental mild cognitive impairment, Alzheimer's disease and vascular dementia in elderly.

To examine the association between body mass index (BMI) and cognitive decline (CD) due to Mild Cognitive Impairment (MCI), Alzheimer's Disease (AD), and Vascular Dementia (VaD). The subjects aged ≥ 65 years were recruited prospectively from the Geriatrics Clinic of Gulhane Medical School, between 2004 and 2008 years. 1302 patients were included in the study. Cognitive status, clinical diagnosis of CD (MCI, AD, and VaD) and clinical and environmental risk factors were evaluated by comprehensive geriatric assesment. Finally, the subjects were categorized into two groups according to having CD or not. 905 (69.5%) subjects were not having CD whereas 397 (30.5%) patients with CD. Of the patients with CD, 140 (10.4%) had MCI, 227 (16.9%) AD, and 30 (2.2%) VaD. After adjustment for confounding with a model for multiple regression analysis, age (OR=1.054; CI:1.027-1.083; p < 0.001) and family history of dementia (OR=1.662; CI:1.038-2.660; p=0.034) were found to be independent risk factors for CD. Also, overweight (OR=0.594; CI:0.370-0.952; p=0.03) and obese (OR=0.396; CI:0.242-0.649; p < 0.001), and high education level (OR=0.640; CI:0.451-0.908; p=0.012) were found to be independent protective factors for CD. We found the risk of CD decreases in overweight and obese elderly. The results indicate that the primary prevention should not only consider risk factors, but must also take anthropometric data into consideration in order to identify persons at high risk for CD.

Demenz und Delirium

Dementia and delirium are nosologic entities with overlapping presenting symptoms. The diagnostic criteria of dementia and of mild cognitive impairment-conceptualized as prodromal state of dementia-are discussed here and the importance of very early diagnosis of cognitive decline and the integration of information from informants in the diagnostic process is highlighted. Prominent features of vascular dementia and of dementia with Lewy bodies which are important for differential diagnosis and therapy are described.

Ineffectiveness of an Italian NART-equivalent for the Estimation of Verbal Learning Ability in Normal Elderly

Comparison between current and premorbid memory ability may be of help when trying to make a timely diagnosis of cognitive decline in questionable dementia. In the present study, we evaluated the possibility of estimating episodic verbal memory scores at the Rey Auditory Verbal Learning Test (RAVLT) from an irregular words reading task held to resist to deterioration, that is the Italian analogue of the NART, the TIB (Test d’Intelligenza Breve - brief intelligence test). A regression analysis was performed in a large sample of healthy elderly, using RAVLT scores as dependent variable and TIB score, MMSE score, age and education as predictors. We failed to find a relationship between the two tests that was strong enough for a reliable estimation of memory ability.