The indirect effect of positive aspects of caregiving on the relationship between cognitive decline and dementia caregiver burden

Background

Research has linked increased cognitive decline in a dementia care recipient to worsening caregiver burden, but the presence of positive aspects of caregiving is associated with better outcomes. As cognitive decline worsens, a lack of positive caregiving experiences could lead to burden for the caregiver. This study investigated relationships among dementia caregiver burden, cognitive decline, and positive aspects of caregiving in dementia, predicting an indirect effect of positive aspects of caregiving.

Methods

Data from 724 patients of an outpatient memory clinic in Ohio were examined and dyads included based on clinically supported patient diagnoses on the dementia spectrum. Caregivers completed the Zarit Burden Interview (ZBI) and Positive Aspects of Caregiving (PAC) measures. The Montreal Cognitive Assessment and Mini-Mental State Examination were used to estimate cognitive decline, standardized to create a single variable. Multiple potential covariates were considered for inclusion in the model. A cross-sectional mediation analysis using the Hayes PROCESS macro explored the presence of an indirect effect of PAC on the relationship between cognitive decline and ZBI using 5000 bootstrap samples.

Results

Only the potential covariate caregiver age was correlated with any of the primary variables; this variable was controlled in analyses. Significant relationships emerged between cognitive decline and ZBI (r = −0.12, P < 0.001), between PAC and ZBI (r = −0.23, P < 0.001), and between cognitive decline and PAC (r = −0.07, P < 0.05). An indirect effect of positive aspects of caregiving on the relationship between cognitive decline and ZBI was statistically significant (B = 0.0092, 95% bias-corrected confidence interval: 0.0008, 0.0185), accounting for 14.4% of the variance in the model.

Conclusions

A lack of positive aspects of caregiving could be partially responsible for development of dementia caregiver burden as cognitive decline worsens. Longitudinal examination of these relationships is needed to understand causality fully. Findings may help healthcare providers tailor treatment to alleviate caregiver burden.     

Platelet MAO-B activity and vitamin B12 in old age dementias

Platelet MAO-B activity, serum vitamin B₁₂ levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B₁₂ levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B₁₂ levels (Group I: <200 pg/mL; Group II: ≥200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B₁₂ and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.     

Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth

Vitamin B₁₂ and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B₁₂ and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B₁₂ and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B₁₂ and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n = 8 each): control, vitamin B₁₂ deficient, vitamin B₁₂ deficient + omega-3 fatty acid, vitamin B₁₂ supplemented, vitamin B₁₂ supplemented + omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B₁₂ deficiency showed lower (p < 0.05) pup brain mRNA and protein levels (p < 0.01) of VEGF, higher (p < 0.01) HIF-1 alpha protein levels, lower (p < 0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B₁₂ deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B₁₂ supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B₁₂ supplemented group showed higher (p < 0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B₁₂ and omega-3 fatty acids both influence the levels and expression of neurotrophins and angiogenic factors in the offspring brain suggesting a possible benefit of combined maternal supplementation of these vital nutrients.     

The relationship between impairment of voluntary movements and cognitive impairment in Huntington’s disease

The relationship between motor symptoms and cognitive impairment in Huntington’s disease (HD) is still discussed. We analysed 45 HD patients in various stages using Unified Huntington’s Disease Rating Scale motor subscale (voluntary and involuntary components were evaluated separately), verbal memory and executive functions tests. Partial correlations controlling for HD duration and age were used to estimate the relationships among factor scores for motor and cognitive impairment. Voluntary components of motor performance were found to be significantly correlated with verbal short-term memory disturbances (r = −0.361, P = 0.03), with tests of executive functions more dependent on motor performance (r = 0.640, P < 0.01) and also with tests of executive functions less dependent on motor performance (r = 0.461, P < 0.01). Involuntary components did not correlate significantly with any part of cognitive performance.     

The combination of vitamin D<Subscript>3</Subscript> and dehydroascorbic acid administration attenuates brain damage in focal ischemia

The aim of this study is to determine the protective effects of vitamin D₃ and dehydroascorbic acid (DHA), a blood-brain barrier transportable form of vitamin C, against ischemia/reperfusion (I/R) injury on a middle cerebral artery occlusion/reperfusion model of brain since reactive oxygen species play an important role in the pathophysiology of I/R injury in brain. In order to examine antioxidant status and lipid peroxidation, we assayed malondialdehyde (MDA) levels as a marker of lipid peroxidation, and reduced glutathione (GSH) and superoxide dismutase (SOD) enzyme activities as free radical scavenging enzymes in cortex and corpus striatum (CS). Wistar albino rats were divided into five equal groups of each consisting of seven rats: control, I/R, I/R + DHA, I/R + vitamin D₃, and I/R + vitamin D₃ + dehydroascorbic acid groups. MDA levels were found to be increased in the I/R group, I/R + DHA, and I/R + vitamin D₃ groups compared with the control group in both cortex and corpus striatum. However, MDA level were found to be significantly decreased in only I/R + vitamin D₃ + DHA group compared with the I/R group in cortex (P < 0.0001). MDA levels were not significantly different in I/R + DHA, and I/R + vitamin D₃ groups compared with the I/R group. GSH and SOD enzyme activities were significantly decreased in I/R, I/R + DHA, and I/R + vitamin D₃ groups compared with the control group in both cortex and corpus striatum (CS) (P < 0.0001). Whereas, both GSH and SOD activity were increased in I/R + vitamin D₃ + DHA group compared with the I/R group in both cortex and CS (P < 0.001 in cortex, P < 0.001 in CS for SOD P < 0.002 in cortex P < 0.03 in CS for GSH). Our results demonstrate that the combination of vitamin D₃ and DHA treatment prevent free radical production and dietary supplementation of vitamin D₃ and DHA which may be useful in the ischemic cerebral vascular diseases.     

Dementia and subnormal levels of vitamin B12: Effects of replacement therapy on dementia

Routine determination of serum vitamin B₁₂ levels is generally recommended as part of the screening of demented patients, based on the notion that vitamin B₁₂ deficiency is one of the causes of reversible dementia. We studied the effects of vitamin B₁₂ replacement therapy in a prospective longitudinal study at a memory clinic, with special emphasis on assessment of severity of dementia: not only cognitive deterioration, but also disability in the activities of daily life, behavioural problems, and the burden experienced by the caregiver were examined using instruments of proven validity. In a series of 170 consecutive patients with dementia, subnormal serum vitamin B₁₂ levels were found in 26 cases (15%); all but one fulfilled diagnostic criteria for possible Alzheimer's disease. Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months. When the size and pattern of individual change scores, and the mean change scores on all instruments were taken into account, functioning after replacement therapy was not improved. When change scores of treated patients were compared with those of patients with Alzheimer's disease (n = 69), vitamin B₁₂ replacement did not result in slowing of the progression of dementia. Contrary to widely accepted beliefs, subnormal serum vitamin B₁₂ levels are not a (quantitatively) important cause of reversible dementia.     

Role of vitamin B12, folate, and thyroid stimulating hormone in dementia: A hospital-based study in north Indian population

Background:

Vitamin B₁₂ and folate represent modifiable risk factors for dementia. They may increase the risk of Alzheimer′s dementia (AD) and vascular dementia (VaD) as their deficiency can increase the homocysteine level due to slowed methylation reaction. Homocysteine has a neurotoxic effect that could lead to neurologic disturbances. Hence, it is important to explore the status of serum B₁₂ and folate in AD and VaD to evolve the treatment strategies for the same.

Objectives:

A retrospective study was conducted to assess the levels of vitamin B₁₂, folate, and thyroid stimulating hormone (TSH) in serum and the relationship of these factors, including age and sex to cognitive decline in VaD, AD, and dementia due to other causes (DOC).

Materials and Methods:

Serum vitamin B₁₂, folate, TSH, and total cholesterol were studied in 32 AD patients (mean age: 65 years), 12 VaD patients (mean age: 61 years), 83 DOC (mean age: 65 years), and 127 control subjects (mean age: 49 years). Results: In AD, VaD, and DOC, the levels of vitamin B₁₂ and folate were significantly lower (P < 0.002; 0.026; 0.002 for vitamin B₁₂ and P < 0.000 in all the 3 groups for folate) as compared with the controls. Similarly, TSH levels were significantly lower in AD and DOC (P < 0.008; 0.038) as compared with the controls.

Conclusion:

Vitamin B₁₂ and folate were significantly low in both AD and VaD patients. Hence, B vitamin supplementation should be considered as possible targets for the therapeutic intervention in dementia.     

Utility of measuring vitamin B<Subscript>12</Subscript> and its active fraction,holotranscobalamin, in neurological vitamin B<Subscript>12</Subscript> deficiency syndromes

Vitamin B₁₂ (VitB₁₂, cobalamin) deficiency has been associated with various neuropsychiatric conditions, such as peripheral neuropathy, subacute combined degeneration, affective disorders, and cognitive impairment. Current assays analyze vitamin B₁₂, of which only a small percentage is metabolically active. Measurement of its active fraction, holotranscobalamin, might be of greater relevance, but data in populations with neuropsychiatric populations are lacking. In this study, in order to validate VitB₁₂ and holotranscobalamin (holoTC) serum levels for the detection of VitB₁₂ deficiency in neuropsychiatric conditions, we compared the validity of VitB₁₂ and holoTC in a patient cohort with neuropsychiatric conditions suspicious for VitB₁₂ deficiency. The cohort included all patients admitted to the Department of Neurology at our university between 2005 and 2009 with at least two parameters of the VitB₁₂ metabolism available (n = 1,279). We used elevated methylmalonic acid as the external validation criterion for VitB₁₂ deficiency and restricted our analyses to subjects with normal renal function. Among all normal renal function patients, 13.2% had VitB₁₂ deficiency. In receiver operating characteristic curve (ROC) analysis, correlation of VitB₁₂ and holoTC with vitamin B₁₂ deficiency was generally weak, and the areas under the curve (AUC) were not significantly different for holoTC compared to vitamin B₁₂ in all subjects (AUC: 0.66 [95%CI: 0.51–0.82]; p = 0.04 vs. 0.72 [0.65–0.78], p < 0.0001) and in subcohorts of patients with classical VitB₁₂ deficiency syndromes. The positive predictive values for holoTC and vitamin B₁₂ were low (14.7 vs. 21.0%) and both were associated with more false-positive than true-positive test results. holoTC does not show superior diagnostic accuracy compared to VitB₁₂ for the detection of VitB₁₂ deficiency in subjects with neuropsychiatric conditions. Neither test can be recommended to diagnose VitB₁₂ deficiency in subjects with neuropsychiatric disorders.     

To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer’s disease

Background  Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD. Methods  We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov—). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI_95% 0.66–0.87], z = −3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI_95% [1.24–1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI_95% 0.83–1.09], z = −0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI_95% 0.63–1.70, z = 0.16, P = 0.86). Conclusion  The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.     

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China

BackgroundThe impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinson's disease (PD) in the Chinese population are largely unknown.ObjectivesTo study the impact of NMS on the HRQoL in Chinese PD patients.MethodsA total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinson's disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD.ResultsThe mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (r_s = 0.71, P < 0.01), sleep/fatigue domain (r_s = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (r_s = 0.55, P < 0.01), attention/memory (r_s = 0.42, P < 0.01), gastrointestinal (r_s = 0.44, P < 0.01) and Miscellany domains (r_s = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (r_s = 0.71, P < 0.01), emotional well-being (r_s = 0.62, P < 0.01), cognitions (r_s = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (r_s = 0.45, P < 0.01), activities of daily living (r_s = 0.43, P < 0.01), stigma (r_s = 0.42, P < 0.01), communication (r_s = 0.47, P < 0.01), bodily discomfort (r_s = 0.46, P < 0.01) and the total score of NMSS. Female, H–Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients.ConclusionsNMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.     

Lack of modulatory effect of short-term repeated electroconvulsive therapy on platelet vesicular monoamine transporter 2 (VMAT2) in depressed patients

We investigated the effect of electroconvulsive therapy (ECT) on platelet vesicular monoamine-transmitter-transporter 2 (pVMAT2) using high-affinity [³H]dihydrotetrabenazine binding to platelet VMAT2 in 11 women and 7 men, aged 53.7 ± 15.8. The Hamilton Depression Rating Scale (HAM-D) and the binding characteristic of pVMAT2 were assessed before and after six ECTs, administered over 21 days. A significant reduction (4.5 ± 0.46; 20.8%) was obtained in HAM-D scores (p < 0.01) following the ECTs. The pVMAT2 density (B _max) and affinity values (K _d) remained unaltered. Six ECTs are not sufficient for modulation in pVMAT2 expression. Long-term studies are needed to clarify the relationship between full remission and possible alterations in platelet/brain VMAT2 characteristics.     

Use of the frontal assessment battery in evaluating executive dysfunction in patients with Huntington’s disease

The frontal assessment battery (FAB) is a bedside cognitive scale designed to measure executive functions. Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive dysfunction. The aim of this study was to check the validity of the FAB for the evaluation of cognitive impairment in patients with HD. Forty-one patients diagnosed with HD and 53 healthy controls matched by education, sex and age were evaluated with a validated Brazilian version of the UHDRS, the VFT, the SDMT, the SIT, the MMSE, and the FAB. The diagnosis of HD was made by DNA analysis. FAB scores were lower in patients than in the controls (p < 0.001) and had significant correlations with the VFT (r = 0.79; p < 0.05), the SDMT (r = 0.80; p < 0.05), the SIT (r = 0.72; p < 0.05), the MMSE (r = 0.83; p < 0.05), the FCS (r = 0.79; p < 0.05) and the motor section of the UHDRS (r = −0.80; p < 0.05). The FAB differentiated between HD patients in the initial and later stages of the disease. The one-year longitudinal evaluation revealed a global trend toward a worsening in the second score of the FAB. The results demonstrate that the FAB presents good internal consistency and also convergent and discriminative validity; therefore it is a useful scale to assess executive functions and to evaluate cognitive impairment in patients with HD.     

Increased Cerebrospinal Fluid F<Subscript>2</Subscript>-Isoprostanes are Associated with Aging and Latent Alzheimer’s Disease as Identified by Biomarkers

Alzheimer’s disease (AD) is a common age-related chronic illness with latent, prodrome, and fully symptomatic dementia stages. Increased free radical injury to regions of brain is one feature of prodrome and dementia stages of AD; however, it also is associated with advancing age. This raises the possibility that age-related free radical injury to brain might be caused in part or in full by latent AD. We quantified free radical injury in the central nervous system with cerebrospinal fluid (CSF) F₂-isoprostanes (IsoPs) in 421 clinically normal individuals and observed a significant increase over the adult human lifespan (P < 0.001). Using CSF amyloid (A) β₄₂ and tau, we defined normality using results from 28 clinically normal individuals <50 years old, and then stratified 74 clinically normal subjects ≥60 years into those with CSF that had normal CSF Aβ₄₂ and tau (n = 37); abnormal CSF Aβ₄₂ and tau, the biomarker signature of AD (n = 24); decreased Aβ₄₂ only (n = 4); or increased tau only (n = 9). Increased CSF F₂-IsoPs were present in clinically normal subjects with the biomarker signature of AD (P < 0.05) and those subjects with increased CSF tau (P < 0.001). Finally, we analyzed the relationship between age and CSF F₂-IsoPs for those clinically normal adults with normal CSF (n = 37) and those with abnormal CSF Aβ₄₂ and/or tau (n = 37); only those with normal CSF demonstrated a significant increase with age (P < 0.01). These results show that CSF F₂-IsoPs increased across the human lifespan and that this age-related increase in free radical injury to brain persisted after culling those with laboratory evidence of latent AD.     

Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone

Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59,P = 0.0084) between serum vitamin B₁₂ and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of Viamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B₁₂ and folate were below the reference medians. We hypothesize that low or reduced vitamin B₁₂/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low Viamin B₁₂/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B₁₂ and folate metabolism in patients with MS.     

Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring

Altered maternal micronutrients (folic acid, vitamin B₁₂) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B₁₂ and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B₁₂) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B₁₂. Both the vitamin B₁₂ deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B₁₂ deficient diet) increases (p < 0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p < 0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p < 0.05) the levels of brain DHA in both the vitamin B₁₂ deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.     

Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency

Background: Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B₁₂ deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. Observation: A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B₁₂ deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B₁₂ supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. Conclusion: Leukoencephalopathy and dementia should raise the suspicion of a vitamin B₁₂ deficiency because vitamin B₁₂ supplementation may result in at least partial clinical improvement.     

Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives

Cognitive dysfunction is increasingly recognized as a significant long-term complication following subarachnoid hemorrhage (SAH), affecting up to 60% of survivors. We proposed to determine the incidence and explore potential mechanisms of cognitive dysfunction in a rat model. The effects of intracisternal blood, saline and sham injections were compared. At five weeks, Morris water maze escape latency (P = 0.001) and swimming distance (P = 0.001) were significantly different between groups, with increased latencies and distances recorded in the blood group in spite of increased swimming speed. The number of morphologically intact cortical (r = − 0.75, P = 0.0001) and hippocampal CA1 (r = − 0.80, P < 0.0001) neurons correlated with escape latency. In spite of only slight early reductions in proximal cerebral arterial diameters, pronounced and prolonged reductions in regional cerebral blood flow were observed in SAH rats, suggesting microvascular dysfunction. In concordance, cerebral microangiographic perfusion remained incomplete even after 2 weeks. 8-hydroxydeoxyguanosine immunohistochemistry also revealed microvascular as well as neuronal oxidative DNA damage. These results provide new insights into the pathogenesis of cognitive dysfunction in SAH. They reveal a surprisingly prolonged time course of diffuse cerebrovascular insufficiency, most likely due to reversible microvascular dysfunction. Similar to findings in experimental models of vascular dementia, the data indicate a potentially important role for prolonged cerebrovascular insufficiency, probably due to microvascular dysfunction, and selective cortical and subcortical neuronal loss in cognitive failure following SAH.     

Higher vitamin B12 level at Parkinson's disease diagnosis is associated with lower risk of future dementia

IntroductionTo determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.MethodsWe utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.ResultsPD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44–0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60–0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05).ConclusionHigher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.     

Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment

Objectives

To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI).

Methods

Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aβ_1–42), total tau (t‐tau), and phosphorylated tau (p‐tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non‐SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group.

Results

As compared to the non‐SSD group, the SSD group displayed lower CSF Aβ_1–42 levels (β = ?24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t‐tau (P = 0.497) or p‐tau levels (P = 0.392). Lower CSF Aβ_1–42 levels were associated with poorer performance on learning (β = 0.041, S.E. = 0.018, P = 0.021) and memory (β = ?0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t‐tau levels were associated with poorer performance on measures of global cognition (β = 0.022, S.E = 0.008, P = 0.007) and language (β = ?0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05).

Conclusions

MCI participants with SSD displayed diminished CSF Aβ_1–42 levels but did not differ from non‐SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.     

Dementia‐related restlessness: relationship to characteristics of persons with dementia and family caregivers

Objective

Dementia‐related restlessness is commonly endorsed by caregivers but not well understood. This study examines differences in characteristics (demographics, cognitive status, physical function, pain, and mood) of persons with dementia whose caregivers endorse restlessness versus those who do not. We also examine the relationship of restlessness to caregiver well‐being including burden, upset with behaviors, mastery, and depressive symptomatology.

Methods

We combined baseline data from three caregiver intervention studies of community‐dwelling persons with dementia who exhibited neuropsychiatric symptoms (n = 569) as measured by the Agitated Behaviors in Dementia Scale. We conducted bivariate correlations and independent t‐tests by using the Agitated Behaviors in Dementia Scale restlessness item.

Results

Nearly 65% (n = 367) of dementia caregivers reported restlessness. There were no significant differences between those with and without (n = 202) reported restlessness concerning functional status (physical or cognitive). However, persons with restlessness had significantly higher pain scores (p < 0.01), were more likely to be on behavioral medications (p < 0.001), and had more neuropsychiatric symptoms as compared with persons without restlessness (M = 11.11, nonrestless; M = 6.61, restless) (p < 0.001). Caregivers of persons with dementia‐related restlessness reported greater burden (p < 0.001), behavioral upset (p < 0.001), depression (p < 0.001), and lower mastery providing care (p < 0.01) compared with caregivers of persons without dementia‐related restlessness.

Conclusions

Restlessness is a common neuropsychiatric symptom that appears to be associated with poorer functioning in persons with dementia and greater distress in their caregivers. Further research is needed to understand the unique contributions of restlessness to care burden and quality of life of persons with dementia, as well as ways to address this distressing symptom. Copyright © 2017 John Wiley & Sons, Ltd.