Later Development Of Dementia Research Articles

Behavioural Deficits and Regional Cerebral Perfusion Map in Cognitively Normal and Pre‐Dementia Stages

AbstractBackgroundOur previous work has shown increased presence of early behavioural impairment in Asian than Western cohorts(Soo et al.,2021). Such impairments include mild behavioural changes, sleep disruptions and higher depression, anxiety and stress, in turn representing an at‐risk state which may predict later development of dementia(Müller‐Spahn,2003;Soo et al.,2021). Additionally, growing evidence illustrates that cerebrovascular changes are a key component in the pathological sequelae and may be detectable years before clinical presentation of dementia (de la Torre,2018). However, the influence of cerebral perfusion on behaviour, especially in pre‐dementia stages remains to be elucidated. Thus, we examined the association between regional grey matter perfusion and behaviour in cognitively normal(CN) and subjects with mild cognitive impairment(MCI) or subjective cognitive decline(SCD). We hypothesized that grey matter perfusion deficits would be related to behaviour impairment even in early stages of SCD/MCI.MethodWe studied 35 CN and 248 pre‐dementia (MCI/SCD) from a community‐based research cohort from the Dementia Research Centre (Singapore) with neuroimaging, neuropsychological and behavioural assessments(Table 1). We investigated the association between regional grey matter perfusion across 31 regions of interest spanning frontal, parietal, temporal and occipital lobes using 2D pulsed Arterial Spin Labelling and performance on the mild behaviour impairment‐checklist(MBI‐C), Pittsburgh Sleep Quality Index(PSQI) and Depression, Anxiety and Stress Scale(DASS). These associations were examined in CN and MCI/SCD groups separately and respective Pearson’s correlation matrices were derived.ResultOverall, greater behavioural impairment on the MBI‐C, DASS and PSQI was associated with hypoperfusion across multiple grey matter regions. This association was stronger in CN than in the pre‐dementia group. Specifically, among CN, hypoperfusion in the frontal, parietal and occipital lobes related most strongly to greater behavioural impairment, especially MBI‐C and DASS depression(Fig.1). In the MCI+SCD group, only hypoperfusion in the frontal and temporo‐occipital regions related to worse behavioural impairment across the MBI, PSQI and DASS(Fig.2).ConclusionIn this study, we illustrate differential associations between cerebral hypoperfusion and behavioural impairment in CN and MCI/SCD groups, with CN individuals showing more widespread and stronger associations between behavioural impairment and hypoperfusion across the brain. In SCD/MCI, hypoperfusion in frontal and temporo‐occipital regions were associated with behavioural impairment.

Prefrontal hemodynamic features of older adults with preserved visuospatial working memory function

Memory decline has been observed in the aging population and is a risk factor for the later development of dementia. Understanding how memory is preserved in older adults has been an important topic. The present study examines the hemodynamic features of older adults whose memory is comparable with that of young adults. In the present study, 45 younger and 45 older adults performed the visual memory task with various difficulty levels (i.e., the items to be remembered), and their cerebral hemodynamics at each level were measured by functional near-infrared spectroscopy (fNIRS). The results showed that older adults exhibited higher activation than younger adults under more difficult but not easier levels. In addition, older adults whose performance is comparable with that of young adults (i.e., being able to remember six items) showed more right-lateralized activation. However, those unable to do so showed more left-lateralized activation. The results suggested that high-performing older adults possess successful compensatory mechanisms by recruiting cognitive resources in a specialized brain region.

Bipolar disorder progression to dementia with frontal features. A scoping review protocol

Background: A subset of patients with bipolar disorder (BD) develop a midlife cognitive/behavioral decline that overlaps with the clinical features of behavioral variant Frontotemporal Dementia (bvFTD). Several case reports and case series have described different clinical features and outcomes of a frontal cognitive/behavioral decline in patients with history of BD. Given that this presentation is scarcely reported, a first step to better characterize this specific condition is to perform an evidence synthesis report. Objective: This scoping review protocol aims to describe and characterize the different patterns of frontal cognitive/behavioral decline in patients with history of BD. Information sources: Studies will be retrieved from MEDLINE (PubMed), PsychINFO, EMBASE and Google Scholar, no other sources will be considered. Inclusion criteria: Studies describing patients with an established diagnosis of BD preceding a later development of dementia with frontal cognitive/behavioral decline. Exclusion criteria: Studies written in languages different than Spanish or English or French that could not be appropriately translated, or whose full text files could not be retrieved, and studies describing manic or BD symptoms, but not an antecedent history consistent with bipolar disorder, as a clear prodrome of bvFTD diagnosis. Data will be extracted by two researchers and verified by agreement. This protocol complies with the PRISMA-P, PRISMA ScR and JBI manual for evidence synthesis scoping review guidelines.

Late life vascular risk factors and their association with dementia and Alzheimer’s disease

Background : Epidemiological studies have demonstrated associations between higher levels of vascular risk factors in midlife and later development of dementia, particularly Alzheimer's disease (AD). However, in elderly subjects with dementia, some studies have shown that these associations may decrease or even reverse. Therefore , our study aimed to find the association between late life cardiovascular risk factors and neurodegenerative dementia in general and AD in particular. Methods :It is a retrospective case control study using electronic medical records that included elderly patients that were reviewed in Ahmadi hospital geriatric clinic , Kuwait , from the period of 1/7/2019 to 1/2/2020. Two hundred and three (203) elderly patients with neurodegenerative dementia (study group) were recruited for this retrospective study and compared to two hundred and one (201) controls with normal cognition for the presence of vascular risk factors.Results :The study included 404 subjects .Age ranged from 60 to 107 years (mean age 78.79, ± 8.13 SD). AD was found to be the most prevalent type of dementia in the study group , as 49.3 % (100/203) of the demented patients were diagnosed with AD. No significant statistical association was found between vascular risk factors and dementia (P>0.05) , except for obesity which showed negative association (P<0.001). Regarding AD , no statistical significance was found between AD and diabetes, hyperlipidemia, smoking nor atrial fibrillation. On the other hand, we found obesity and hypertension more prevalent in the normal cognition group (negative association with P value <0.001,0.05 respectively). Conclusion : The results of our study support an emerging concept that, while elevated levels of vascular risk factors in midlife increase the risk of development of dementia and AD later in life, once dementia begins , these associations may be diminished or reversed in the elderly

Adolescents’ Health Literacy of Dementia Modifiable Risk Factors in Predominantly Rural Savinjska Region, Slovenia

Objectives: Without information on health literacy of dementia variable risk factors, it is difficult to set a strategy for an education in this field. The purpose of the study was to determine whether adolescents in predominantly rural regions are aware of the dementia variable risk factors and if dementia is discussed in secondary school. Methods: In a total cohort of 1,128 adolescents (aged 14–19) from secondary schools in Slovenia, four-hundred and sixty-four were educated in predominantly rural Savinjska region. They completed a series of questions that assessed their modifiable dementia risk factors knowledge and where they obtained information on dementia. Descriptive analysis and chi-square test were performed, comparing differences between Savinjska region and all Slovenian regions. Results: Respondents from predominantly rural area (n = 464) did not differ in their knowledge of dementia and the risk factors for it (p>0.05). Out of 14 dementia knowledge questions and of six modifiable dementia risk factors questions, respondents answered more than two thirds correctly. In contrast is finding that 84.7 % of total respondents and 82.5 % of respondents from Savinjska region wrongly believe that memory impairment with age is normal. However, interesting finding resulted, namely students from the predominantly rural region talked less about dementia in school classes than others (p<0.05). Conclusions: To reduce the risk of dementia gaps in the adolescent's health literacy must be taken into account. Considering that adolescents are already forming an opinion on modifiable risk factors for the later development of dementia, more effort is needed to embed dementia understanding in the light of its prevention in the secondary school curriculum.

A protocol to assess the risk of dementia among patients with coronary artery diseases using CAIDE score

Introduction: The impact of coronary artery disease (CAD) on the later development of dementia is not well studied globally. Therefore, this study aims to determine the long-term risk of dementia using a mobile application-based tool in addition to elucidating the contributing factors among CAD patients. Protocol: This cross-sectional study collected data from 285 stable CAD patients admitted to the “Ibrahim Cardiac Hospital and Research Institute” for coronary revascularization from August 2019 to July 2020. The patients were recruited using a convenient sampling technique due to economic and logistical issues. Data were collected through a face-to-face interview using a pretested semi-structured questionnaire. Physical parameters (blood pressure and anthropometry) were measured while maintaining the adequate privacy of the patients. The biochemical parameters analyzed by the hospital lab were also collected. The next phase of this study involves the use of a mobile application that uses the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score, to determine the risk factors associated with dementia. In addition, a descriptive statistical and inferential analysis will also be performed to determine the key contributing risk factors linked to the development of dementia. Ethics and dissemination: The study has been reviewed and approved by the Ethical Review Committee of Bangladesh University of Health Sciences. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, online news portal, the internet, and various community/stakeholder engagement activities. Conclusion: As a baseline study of the country, this study will fill a key knowledge gap in the pathway to the development of better interventions for dementia in Bangladesh. Outcomes from this study will also help with raising awareness on the association of mental health-related issues with cardiovascular diseases so that an improved cardiac rehabilitation program can be implemented in Bangladesh.

A protocol to assess the risk of dementia among patients with coronary artery diseases using CAIDE score

Introduction: The impact of coronary artery disease (CAD) on the later development of dementia is not well studied globally. Therefore, this study aims to determine the long-term risk of dementia using a mobile application-based tool in addition to elucidating the contributing factors among CAD patients. Protocol: This cross-sectional study collected data from 285 stable CAD patients admitted to the “Ibrahim Cardiac Hospital and Research Institute” for coronary revascularization from August 2019 to July 2020. The patients were recruited using a convenient sampling technique due to economic and logistical issues. Data were collected through a face-to-face interview using a pretested semi-structured questionnaire. Physical parameters (blood pressure and anthropometry) were measured while maintaining the adequate privacy of the patients. The biochemical parameters analyzed by the hospital lab were also collected. The next phase of this study involves the use of a mobile application-based tool, “The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)” risk score, to determine the risk factors associated with dementia. In addition, a descriptive statistical and inferential analysis will also be performed to determine the key contributing risk factors linked to the development of dementia. Ethics and dissemination: The study has been reviewed and approved by the Ethical Review Committee of Bangladesh University of Health Sciences. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, online news portal, the internet, and various community/stakeholder engagement activities. Conclusion: As a baseline study of the country, this study will fill a key knowledge gap in the pathway to the development of better interventions for dementia in Bangladesh. Outcomes from this study will also help with raising awareness on the association of mental health-related issues with cardiovascular diseases so that an improved cardiac rehabilitation program can be implemented in Bangladesh.

Aβ42 mediated activation of the NLRP3 inflammasome predicts cognitive and gait performance in midlife type 2 diabetes mellitus (T2DM)

AbstractBackgroundMidlife Type 2 Diabetes Mellitus (T2DM) is a potent risk factor for later development of dementia. However, putative mechanisms mediating this risk are poorly understood. The NLRP3 inflammasome receptor, which drives strong pro‐inflammatory responses, has been implicated in both T2DM and Alzheimer’s disease (AD) pathogenesis, and can be activated by Amyloid β1‐42 (Aβ42).MethodPeripheral Blood Mononuclear Cells (PBMCs) were isolated from participants with T2DM (N = 39; 52.04 ± 8.01 years) and matched controls (N = 21; 52.16 ± 7.82 years) without any evidence of cognitive impairment. PBMCs were incubated for 18 hours under the following conditions: (i) Lipopolysaccharide (LPS), (ii) Aβ42, (iii) LPS & Aβ42 and (iv) LPS & Nigericin (potent NLRP3 activator). Cytokine production was measured using ELISA and gene expression using qPCR. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Gait speed was measured under normal and dual‐task conditions (reciting alternate letters of the alphabet). Wilcoxon rank‐sum tests were used for univariate analysis and Poisson and linear regression models used for multivariate analyses, adjusting for important covariates.ResultsTreatment of PBMCs under all four conditions resulted in a significant production of the pro‐inflammatory cytokines IL‐1β and IL‐6, which did not differ between T2DM and healthy controls. Greater IL‐1β production (an NLRP3‐dependent cytokine) under both Aβ‐42 (ii) and LPS & Nigericin (iv) conditions was associated with greater likelihood of error on the MoCA (aIRR 1.01, p = 0.010; aIRR 1.01, p = 0.004). Further, greater IL‐1β production under both LPS & Aβ42 (iii) and LPS & Nigericin (iv) conditions was associated with a greater slowing effect (cost) on the dual‐task (adjusted: β = 0.31, 0.04‐0.58, p = 0.023; 0.029, 0.05 – 0.54, p = 0.019). Effects were seen in the cohort overall, regardless of T2DM status, but were stronger in those with T2DM.ConclusionsGreater activation of the NLRP3 inflamamsome by Aβ42 was associated with poorer cognitive and gait performance in midlife T2DM. Further work will follow this cohort longitudinally and assess the ability of innate immune NLRP3 activity to predict later cognitive trajectories in those with midlife T2DM.

What do we know about the risks of developing dementia after traumatic brain injury?

Traumatic brain injury (TBI) is a risk factor for the later development of dementia, but although the evidence dates back to the early 20th century, the nature of any association and its mechanistic pathways remain unclear. There has been greater focus on this subject over recent years, in part because of increasing reports around sports related TBIs, especially in the USA. Differences in research methods and clinical sampling remain the primary reason for the variable findings, although there is clearly increased prevalence of neurodegenerative disorders in general. Duration of follow up, definition of both TBI and dementia, and differences in the extent to which other dementia risk factors are controlled, as well as concerns about medical record accuracy are all issues yet to be resolved in TBI research, as is an absence pathological evidence. In addition, TBI has been reported to initiate a cascade of pathological processes related to several neurodegenerative disorders, and as such, it is likely that the risks vary between individuals. Given the evidence that dementia risk may increase with injury severity and frequency, a detailed account of age and type of injury, as well as lifetime TBI exposure is essential to document in future studies, and further longitudinal research with biomarker assessments are needed.

A protocol to assess the risk of dementia among patients with coronary artery diseases using CAIDE score

Introduction: The impact of coronary artery disease (CAD) on the later development of dementia is not well studied globally. Therefore, this study aims to determine the long-term risk of dementia using a mobile application-based tool in addition to elucidating the contributing factors among CAD patients. Protocol: This ongoing cross-sectional study is collecting data from 285 stable CAD patients admitted to the “Ibrahim Cardiac Hospital and Research Institute” for coronary revascularization from August 2019 to July 2020. The patients were recruited using a convenient sampling technique due to economic and logistical issues. Data were collected through a face-to-face interview using a pretested semi-structured questionnaire. Physical parameters (blood pressure and anthropometry) were measured while maintaining the adequate privacy of the patients. The biochemical parameters analyzed by the hospital lab were also collected. The next phase of this study involves the use of a mobile application-based tool, “The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)” risk score, to determine the risk factors associated with dementia. In addition, a descriptive statistical and inferential analysis will also be performed to determine the key contributing risk factors linked to the development of dementia. Ethics and dissemination: The study has been reviewed and approved by the Ethical Review Committee of Bangladesh University of Health Sciences. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, online news portal, the internet, and various community/stakeholder engagement activities. Conclusion: As a baseline study of the country, this study will fill a key knowledge gap in the pathway to the development of better interventions for dementia in Bangladesh. Outcomes from this study will also help with raising awareness on the association of mental health-related issues with cardiovascular diseases so that an improved cardiac rehabilitation program can be implemented in Bangladesh.

A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort

BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1 year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61 years (interquartile range, IQR 43–72). The patients were followed for up to 11 years (median 3.9 years, IQR 1.7–6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p < 0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91–1.11, p = 0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

Are symptoms of insomnia in primary care associated with subsequent onset of dementia? A matched retrospective case-control study

Objective: There is evidence from neuroimaging studies of an association between insomnia and early dementia biomarkers, but observational studies have so far failed to show a clear association between insomnia and the later development of dementia. We investigated the association between dementia diagnosis and recording of insomnia symptoms 5–10 years earlier in primary care.Method: A case-control study using data from the Clinical Practice Research Datalink. 15,209 cases with dementia (either Alzheimer’s, vascular, mixed or non-specific subtypes) at least 65 years old at time of diagnosis, were matched with the same number of controls on year of birth and gender. We ascertained the presence of insomnia symptoms during a five-year period starting 10 years before the index date. Odds ratios for developing dementia were estimated using logistic regression after controlling for hypnotic exposure and physical and mental health comorbidities.Results: The adjusted odds ratio for dementia in those with previous insomnia was 1.34 (95% CI = 1.20–1.50).Conclusion: There is an association between dementia and previous insomnia. It may be possible to incorporate insomnia into predictive tools for dementia.

Non-pharmacological interventions for cognition in patients with Type 2 diabetes mellitus: a systematic review.

Midlife Type II diabetes mellitus (T2DM) is an important yet often unrecognized risk factor for the later development of dementia. We conducted a systematic review to assess the efficacy of non-pharmacological interventions (namely diet, exercise and cognitive training) for T2DM on cognition. A search strategy was constructed and applied to four databases: EMBASE, Medline, CINAHL and Web of Science. Peer-reviewed journal articles in English were considered assessing the effect of exercise, dietary or cognitive training/stimulation-based interventions (or any combination of these) in patients with T2DM on cognition. Results were dual-screened and extracted by two independent reviewers. Of 4820 results, 3782 remained after de-duplication. Forty full-texts were screened and two studies were included in the final review. The first assessed the impact of a 10-year intensive lifestyle intervention on T2DM-related complications (Look-AHEAD study) and the second was a post hoc analysis of T2DM patients from a trial of a physical activity intervention in older non-demented adult with functional limitations (LIFE study). Whilst the Look-AHEAD study found no impact on diagnosis of mild cognitive impairment or dementia, the LIFE study demonstrated beneficial effects on global cognitive function and delayed memory specifically in older adults with T2DM. There is insufficient evidence to fully assess the effect of non-pharmacological interventions on cognition in T2DM. Well-constructed trials must be designed to specifically assess the effect of non-pharmacological and multi-domain interventions for cognition in patients with T2DM in midlife. All trials examining interventions in T2DM should consider cognition as at least a secondary outcome.

How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder.

We describe the progression of cognitive decline and identify the predictive values of cognitive tests in three groups of REM sleep behavior disorder (RBD) patients classified at their last follow-up as having Parkinson's disease (PD), dementia with Lewy bodies (DLB), or still-idiopathic. Patients (n = 109) underwent polysomnographic, neurological, and neuropsychological assessments. We used linear mixed-model analyses to compare the progression of cognitive test performance between the three groups over a 3-year prodromal period, and performed linear regressions for a 6-year prodromal period. We compared the proportions of patients with clinically impaired performance (z scores < -1.5). DLB patients were pair-matched according to age, sex, and education to healthy controls (2:1 ratio), and receiver operating characteristic curves were performed to identify the psychometric properties of cognitive tests to predict dementia. At follow-up, 38 patients (35%) developed a neurodegenerative disorder: 20 had PD and 18 DLB. Cognitive performance changes over time were strongly associated with later development of dementia. Clear deficits in attention and executive functions were observed 6 years before diagnosis. Verbal episodic learning and memory deficits started later, deviating from normal approximately 5 to 6 years and becoming clinically impaired at 1 to 2 years before diagnosis. Visuospatial abilities progressed variably, with inconsistent prodromal latencies. The Trail Making Test (part B), Verbal Fluency (semantic), and Rey Auditory-Verbal Learning Test (total, immediate, and delayed recalls) were the best predictors for dementia (area under the curve = 0.90-0.97). Prodromal DLB is detectible up to 6 years before onset. For clinical utility, the Trail Making Test (part B) best detects early prodromal dementia stages, whereas Verbal Fluency (semantic) and verbal episodic learning tests are best for monitoring changes over time. Ann Neurol 2018;83:1016-1026.

Demenz und Altersdepression

In old age, depression is often associated with cognitive impairment, ­dementia is associated with depressive symptoms, depressive symptoms can precede a dementia syndrome, and depression and dementia can ­occur ­together. In addition, depressive disorders increase the risk for the later development of dementia. The current evidence for the benefit of clinical findings, and neuropsychological, neurochemical and imaging ­biomarkers for the differentiation of dementia and depression, as well as for the prognosis of depression with regard to the risk of dementia is ­presented. In addition, current pharmacotherapy and psychotherapy of ­depression in demented patients is summarised. There is an urgent need for research to elucidate clinical and biological features in older people with depressive disorders who are at an increased risk of developing ­dementia.

Cluster analysis of cognitive performance in a sample of patients with Parkinson's disease.

BackgroundCognitive impairment is a common feature of Parkinson's disease (PD). The diagnoses of mild cognitive impairment (MCI) in patients with PD implies an increased risk for later development of dementia, however, it is unclear whether a specific type of cognitive loss confers increased risk for faster cognitive decline.ObjectiveDetermine whether it was possible to identify distinct cognitive phenotypes in a sample of patients with PD.MethodsA cross-sectional evaluation of 100 patients with PD recruited from a movement disorders clinic was conducted. The patients were evaluated using the simplified motor score of the UPDRS, the Hoehn and Yahr, Schwab and England, Geriatric Depression Scale, Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating Scale, Mini-Mental State Examination, clock drawing test, digit span, word list battery of CERAD, Frontal Assessment Battery and verbal fluency test. We classified the patients as having normal cognition (PDNC), MCI (PDMCI) or dementia (PDD). Data were analyzed using the chi-square test, non-parametric statistics and cluster analysis.ResultsThere were 40 patients with PDD, 39 with PDMCI and 21 with PDNC. Patients with PDD were older, had longer disease duration, lower education and lower MMSE scores. Cluster analysis showed 3 general distinct cognitive profiles that represented a continuum from mild to severe impairment of cognition, without distinguishing specific cognitive profiles.ConclusionCognitive impairment in PD occurs progressively and heterogeneously in most patients. It is unclear whether the definition of the initial phenotype of cognitive loss can be used to establish the cognitive prognosis of patients.

Pumping the Brakes: Neurotrophic Factors for the Prevention of Cognitive Impairment and Dementia after Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of disability and death worldwide, affecting as many as 54,000,000-60,000,000 people annually. TBI is associated with significant impairments in brain function, impacting cognitive, emotional, behavioral, and physical functioning. Although much previous research has focused on the impairment immediately following injury, TBI may have much longer-lasting consequences, including neuropsychiatric disorders and cognitive impairment. TBI, even mild brain injury, has also been recognized as a significant risk factor for the later development of dementia and Alzheimer's disease. Although the link between TBI and dementia is currently unknown, several proposed mechanisms have been put forward, including alterations in glucose metabolism, excitotoxicity, calcium influx, mitochondrial dysfunction, oxidative stress, and neuroinflammation. A treatment for the devastating long-term consequences of TBI is desperately needed. Unfortunately, however, no such treatment is currently available, making this a major area of unmet medical need. Increasing the level of neurotrophic factor expression in key brain areas may be one potential therapeutic strategy. Of the neurotrophic factors, granulocyte-colony stimulating factor (G-CSF) may be particularly effective for preventing the emergence of long-term complications of TBI, including dementia, because of its ability to reduce apoptosis, stimulate neurogenesis, and increase neuroplasticity.

Cerebrospinal Fluid Fatty Acid-Binding Protein 3 is Related to Dementia Development in a Population-Based Sample of Older Adult Women Followed for 8 Years.

Increased fatty acid-binding protein 3 (FABP-3) levels have been reported in neurodegenerative diseases, including Alzheimer's disease (AD). Cerebrospinal fluid (CSF) FABP-3 has therefore been proposed as a putative marker for dementia. Population-based studies examining whether CSF FABP-3 predicts later development of dementia are lacking. The aim of this study was to examine CSF levels of FABP-3 in relation to later development of dementia in elderly women and in relation to Aβ42, T-tau, P-tau181, and CSF: serum albumin ratio. 86 non-demented women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-93. CSF-FABP-3, Aβ42, T-tau, P-tau181, and the CSF: serum albumin ratio were measured at baseline. Participants were examined with a neuropsychiatric exam at baseline and at follow-up in 2000. Dementia was diagnosed in accordance with DSM-III-R criteria. Between 1992 and 2000, 8 women developed dementia (4 AD, 3 vascular dementia, 1 mixed vascular dementia and AD). Higher levels of CSF-FABP-3 at baseline were related to development of dementia (OR 1.36 CI [1.05-1.76] p = 0.022) and the subtype AD (OR 1.38 CI [1.06-1.82), p = 0.019) during follow-up. FABP-3 correlated with CSF T-tau (r = 0.88, p < 0.001), P-tau181 (r = 0.619, p < 0.001), and CSF:serum albumin ratio (r = 0.233, p = 0.031), but not with Aβ42 (r = -0.08, p = 0.444)CONCLUSION:CSF FABP-3 may be an early marker for later development of dementia, probably related to neuronal degeneration, but independent of Aβ metabolism.

Insulin Resistance Linked to Decreased Brain Metabolism

Insulin resistance was linked to decreased brain glucose metabolism and predicted worse memory function among late–middle-aged adults at risk for Alzheimer's disease, researchers reported online in JAMA Neurology.Based on the findings, “midlife may be a critical period for initiating treatments aimed at preventing or delaying the onset of Alzheimer's disease,” said Auriel A. Willette, PhD, of Iowa State University, Ames, and his associates. Targeting insulin signaling might affect central glucose metabolism and should be studied in presymptomatic Alzheimer's disease, the researchers added.The investigators performed cognitive testing, blood assays, and fludeoxyglucose F18 (FDG)–labeled positron emission tomography (PET) for 150 cognitively normal, late–middle-aged adults who averaged almost 61 years old. In all, 72% of participants were women, 69% had a parent with Alzheimer's disease, about 41% had an APOEε4 allele, and almost 5% had type 2 diabetes mellitus, the investigators reported (JAMA Neurol 2015 July 27 [doi:10.1001/jamaneurol.2015.0613]).Based on the homeostatic model assessment, increased peripheral insulin resistance was significantly associated with decreased glucose metabolism, both globally and in large areas of the frontal, lateral parietal, and medial and lateral temporal lobes, Dr. Willette and his associates found.Insulin resistance and lower glucose uptake were especially robustly associated in the left medial temporal lobe, and lower glucose metabolism in this lobe was associated with worse immediate and delayed memory performance factors. “This finding provides a potential link between insulin resistance and cognitive decline,” they wrote.The findings also support results from previous studies of older adults that have linked insulin resistance, hyperglycemia, and diabetes mellitus to hypometabolism on FDG-PET. “Insulin resistance and hyperglycemia are related conditions, and hyperglycemia, even in the prediabetic range, is associated with a significantly increased risk for later development of dementia,” they noted.The investigators reported no relevant conflicts of interest.Amy Karonis a Frontline Medical News freelance writer based in Albuquerque, NM. Insulin resistance was linked to decreased brain glucose metabolism and predicted worse memory function among late–middle-aged adults at risk for Alzheimer's disease, researchers reported online in JAMA Neurology. Based on the findings, “midlife may be a critical period for initiating treatments aimed at preventing or delaying the onset of Alzheimer's disease,” said Auriel A. Willette, PhD, of Iowa State University, Ames, and his associates. Targeting insulin signaling might affect central glucose metabolism and should be studied in presymptomatic Alzheimer's disease, the researchers added. The investigators performed cognitive testing, blood assays, and fludeoxyglucose F18 (FDG)–labeled positron emission tomography (PET) for 150 cognitively normal, late–middle-aged adults who averaged almost 61 years old. In all, 72% of participants were women, 69% had a parent with Alzheimer's disease, about 41% had an APOEε4 allele, and almost 5% had type 2 diabetes mellitus, the investigators reported (JAMA Neurol 2015 July 27 [doi:10.1001/jamaneurol.2015.0613]).Based on the homeostatic model assessment, increased peripheral insulin resistance was significantly associated with decreased glucose metabolism, both globally and in large areas of the frontal, lateral parietal, and medial and lateral temporal lobes, Dr. Willette and his associates found. Insulin resistance and lower glucose uptake were especially robustly associated in the left medial temporal lobe, and lower glucose metabolism in this lobe was associated with worse immediate and delayed memory performance factors. “This finding provides a potential link between insulin resistance and cognitive decline,” they wrote. The findings also support results from previous studies of older adults that have linked insulin resistance, hyperglycemia, and diabetes mellitus to hypometabolism on FDG-PET. “Insulin resistance and hyperglycemia are related conditions, and hyperglycemia, even in the prediabetic range, is associated with a significantly increased risk for later development of dementia,” they noted. The investigators reported no relevant conflicts of interest. Amy Karonis a Frontline Medical News freelance writer based in Albuquerque, NM.

Abstract P157: Tractography of White Matter Connections Predicts for Vascular Cognitive Impairment in Hypertensive Patients

Vascular cognitive impairment (VCI) results by several vascular risk factors and, particularly, hypertension (HTN). The identification of early changes associated with later development of dementia is demanding. Great part of research has primarily focused on brain changes occuring in grey matter. However, more recent data highlighted that HTN may determine cognitive decline, even before manifest neurodegeneration. Diffusion tensor imaging (DTI) on magnetic resonance, opened the possibility to predict white matter connections that correlate with specific cognitive functions. In this study, we used DTI and cognitive assessment (CA), in order to identify a regional pattern of fractional anisotropy (FA) changes that could predict for VCI in hypertensive patients (HT). We have examined 15 HT (moderate to severe, with antihypertensive medications) vs 15 normotensive (NT), subjecting them to DTI and CA. HT had significant higher SBP (138±4 vs 118±3 in NT) and DBP (87±2 vs 75±2 in NT) (p&lt;0.001), displayed a significant LV hypertrophic remodeling (LVM/BSA 112±5 vs 83±3 for NT) (p&lt;0.0001), with a significant moderate increase in albuminuria (15.7±2.6 mg/24h vs 8.8±1.6 for NT) (p&lt;0.03). When subjected to CA, HT had significantly worsen performance on both MoCA (22.66±0.97 vs 26.21±0.57 NT) and Stroop Test (34.50±3.87 vs 17.75±2.57 NT) (p&lt;0.01). Conversely, tests regarding Verbal Fluency and Instrumental Activities of Daily Living revealed normal performance of HT, thus indicating a selective impairment of memory. Brain imaging showed that, while none of the patients had abnormal signal intensity on T1/T2-weighted MRI, DTI indices FA were significantly reduced in HT as vs NT. In particular, HT had lower FA in projection fibers related to impairment for non-verbal materials (Anterior Thalamic Radiation: 0.358±0.012 vs 0.330±0.006, p&lt;0.05), association fibers involved in executive functioning and emotional regulation (Superior Longitudinal Fasciculus: 0.388±0.013 vs 0.356±0.007, p&lt;0.05), limbic system fibers involved in attention tasks (cingulate gyrus: 0.364±0.009 vs 0.328±0.010, p&lt;0.01). Our data highlight a novel paradigm of combined DTI/CA of HT patients, capable to identify, with great sensitivity, predictive signs of HTN-induced VCI.