[Cognitive Function and Calcium. Structures and functions of Ca2+-permeable channels].
Kaneko Shuji
Clinical calcium
Calcium is essential for living organisms where the increase in intracellular Ca2+ concentration functions as a second messenger for many cellular processes including synaptic transmission and neural plasticity. The cytosolic concentration of Ca2+ is finely controlled by many Ca2+-permeable ion channels and transporters. The comprehensive view of their expression, function, and regulation will advance our understanding of neural and cognitive functions of Ca2+, which leads to the future drug discovery.
CliCa1502181187
Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo.
Olmedillas Del Moral Maria,Asavapanumas Nithi,Uzcátegui Néstor L,Garaschuk Olga
International journal of molecular sciences
Brain aging is characterized by a chronic, low-grade inflammatory state, promoting deficits in cognition and the development of age-related neurodegenerative diseases. Malfunction of microglia, the brain-resident immune cells, was suggested to play a critical role in neuroinflammation, but the mechanisms underlying this malfunctional phenotype remain unclear. Specifically, the age-related changes in microglial Ca signaling, known to be linked to its executive functions, are not well understood. Here, using in vivo two-photon imaging, we characterize intracellular Ca signaling and process extension of cortical microglia in young adult (2⁻4-month-old), middle-aged (9⁻11-month-old), and old (18⁻21-month-old) mice. Our data revealed a complex and nonlinear dependency of the properties of intracellular Ca signals on an animal's age. While the fraction of cells displaying spontaneous Ca transients progressively increased with age, the frequencies and durations of the spontaneous Ca transients followed a bell-shaped relationship, with the most frequent and largest Ca transients seen in middle-aged mice. Moreover, in old mice microglial processes extending toward an ATP source moved faster but in a more disorganized manner, compared to young adult mice. Altogether, these findings identify two distinct phenotypes of aging microglia: a reactive phenotype, abundantly present in middle-aged animals, and a dysfunctional/senescent phenotype ubiquitous in old mice.
10.3390/ijms20030589
The aging mouse brain: cognition, connectivity and calcium.
Radulescu Carola I,Cerar Veronika,Haslehurst Peter,Kopanitsa Maksym,Barnes Samuel J
Cell calcium
Aging is a complex process that differentially impacts multiple cognitive, sensory, neuronal and molecular processes. Technological innovations now allow for parallel investigation of neuronal circuit function, structure and molecular composition in the brain of awake behaving adult mice. Thus, mice have become a critical tool to better understand how aging impacts the brain. However, a more granular systems-based approach, which considers the impact of age on key features relating to neural processing, is required. Here, we review evidence probing the impact of age on the mouse brain. We focus on a range of processes relating to neuronal function, including cognitive abilities, sensory systems, synaptic plasticity and calcium regulation. Across many systems, we find evidence for prominent age-related dysregulation even before 12 months of age, suggesting that emerging age-related alterations can manifest by late adulthood. However, we also find reports suggesting that some processes are remarkably resilient to aging. The evidence suggests that aging does not drive a parallel, linear dysregulation of all systems, but instead impacts some processes earlier, and more severely, than others. We propose that capturing the more fine-scale emerging features of age-related vulnerability and resilience may provide better opportunities for the rejuvenation of the aged brain.
10.1016/j.ceca.2021.102358
[Cognitive Function and Calcium. Intake of calcium and dementia].
Otsuka Mieko
Clinical calcium
Calcium are related to several function in nervous system. Dysfunction of calcium metabolism has been suggested as a pathogenetic participation of the degenerative process. On the other hand, Alzheimer's disease (AD) has been considered a primary neurodegenerative disorder caused by amyloid deposition, although recent epidemiological studies have suggested the partial involvement of cardiovascular risk factors in AD development. Higher self-reported dietary intakes of calcium reduced the risk of all-cause dementia and vascular dementia but not of AD in the general Japanese population, the Hisayama study. A diet rich in calcium and so on may be recommended to lessen the future risk of dementia.
CliCa1502195200
Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.
Datta Dibyadeep,Leslie Shannon N,Wang Min,Morozov Yury M,Yang Shengtao,Mentone SueAnn,Zeiss Caroline,Duque Alvaro,Rakic Pasko,Horvath Tamas L,van Dyck Christopher H,Nairn Angus C,Arnsten Amy F T
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:The etiology of sporadic Alzheimer's disease (AD) requires non-genetically modified animal models. METHODS:The relationship of tau phosphorylation to calcium-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortical neurons using biochemistry and immuno-electron microscopy. The influence of calcium leak from ryanodine receptors (RyRs) on neuronal firing and cognitive performance was examined in aged macaques. RESULTS:Aged monkeys naturally develop hyperphosphorylated tau, including AD biomarkers (AT8 (pS202/pT205) and pT217) and early tau pathology markers (pS214 and pS356) that correlated with evidence of increased calcium leak (pS2808-RyR2). Calcium also regulated early tau phosphorylation in vitro. Age-related reductions in the calcium-binding protein, calbindin, and in phosphodiesterase PDE4D were seen within dlPFC pyramidal cell dendrites. Blocking RyRs with S107 improved neuronal firing and cognitive performance in aged macaques. DISCUSSION:Dysregulated calcium signaling confers risk for tau pathology and provides a potential therapeutic target.
10.1002/alz.12325
Calcium signaling in cognition and aging-dependent cognitive decline.
Oliveira Ana M M,Bading Hilmar
BioFactors (Oxford, England)
Calcium-dependent signals are key triggers of the molecular mechanisms underlying learning and memory and dysregulation of calcium homeostasis in the aging brain has been proposed to underlie aging-dependent cognitive decline. Mechanisms triggered by calcium in neurons include activity-dependent activation of transcription responsible for the synthesis of molecules underlying the long-term changes of neuronal function. Effectors of calcium signaling with a primordial role in transcription regulation are calcium signal-regulated transcription factors. In this review, we summarize the current knowledge of the contribution of key calcium signal-regulated transcription factors, namely CREB, NFAT, and DREAM, to memory formation. We further describe evidence for dysregulation of the activity of these factors during aging.
10.1002/biof.148
The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS): study protocol for a randomised controlled, experimental medicine study.
Atkinson Lauren Z,Colbourne Lucy,Smith Alexander,Harmer Catherine H,Nobre Anna C,Rendell Jennifer,Jones Helen,Hinds Christopher,Mould Arne,Tunbridge Elizabeth M,Cipriani Andrea,Geddes John R,Saunders Kate E A,Harrison Paul J
Trials
BACKGROUND:The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour. METHODS:The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737. DISCUSSION:The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected. TRIAL REGISTRATION:ISRCTN, ISRCTN33631053 . Retrospectively registered on 8 June 2018 (applied 17 May 2018).
10.1186/s13063-019-3175-0
Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life.
The Cochrane database of systematic reviews
BACKGROUND:Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life. OBJECTIVES:To evaluate the effects of vitamin and mineral supplementation on cognitive function in cognitively healthy people aged 40 years or more. SEARCH METHODS:We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov and the WHO Portal/ICTRP from inception to 26th January 2018. SELECTION CRITERIA:We included randomised controlled trials that evaluated the cognitive effects on people aged 40 years or more of any vitamin or mineral supplements taken by mouth for at least three months. DATA COLLECTION AND ANALYSIS:Study selection, data extraction, and quality assessments were done in duplicate. Vitamins were considered broadly in the categories of B vitamins, antioxidant vitamins, and combinations of both. Minerals were considered separately, where possible. If interventions and outcomes were considered sufficiently similar, then data were pooled. In order to separate short-term cognitive effects from possible longer-term effects on the trajectory of cognitive decline, data were pooled for various treatment durations from 3 months to 12 months and up to 10 years or more. MAIN RESULTS:In total, we included 28 studies with more than 83,000 participants. There were some general limitations of the evidence. Most participants were enrolled in studies which were not designed primarily to assess cognition. These studies often had no baseline cognitive assessment and used only brief cognitive assessments at follow-up. Very few studies assessed the incidence of dementia. Most study reports did not mention adverse events or made only very general statements about them. Only 10 studies had a mean follow-up > 5 years. Only two studies had participants whose mean age was < 60 years at baseline. The risk of bias in the included studies was generally low, other than a risk of attrition bias for longer-term outcomes. We considered the certainty of the evidence behind almost all results to be moderate or low.We included 14 studies with 27,882 participants which compared folic acid, vitamin B12, vitamin B6, or a combination of these to placebo. The majority of participants were aged over 60 years and had a history of cardio- or cerebrovascular disease. We found that giving B vitamin supplements to cognitively healthy adults, mainly in their 60s and 70s, probably has little or no effect on global cognitive function at any time point up to 5 years (SMD values from -0.03 to 0.06) and may also have no effect at 5-10 years (SMD -0.01). There were very sparse data on adverse effects or on incidence of cognitive impairment or dementia.We included 8 studies with 47,840 participants in which the active intervention was one or more of the antioxidant vitamins: ß-carotene, vitamin C or vitamin E. Results were mixed. For overall cognitive function, there was low-certainty evidence of benefit associated with ß-carotene after a mean of 18 years of treatment (MD 0.18 TICS points, 95% CI 0.01 to 0.35) and of vitamin C after 5 years to 10 years (MD 0.46 TICS points, 95% CI 0.14 to 0.78), but not at earlier time points. From two studies which reported on dementia incidence, there was low-certainty evidence of no effect of an antioxidant vitamin combination or of vitamin E, either alone or combined with selenium. One of the included studies had been designed to look for effects on the incidence of prostate cancer; it found a statistically significant increase in prostate cancer diagnoses among men taking vitamin E.One trial with 4143 participants compared vitamin D3 (400 IU/day) and calcium supplements to placebo. We found low- to moderate-certainty evidence of no effect of vitamin D3 and calcium supplements at any time-point up to 10 years on overall cognitive function (MD after a mean of 7.8 years -0.1 MMSE points, 95% CI -0.81 to 0.61) or the incidence of dementia (HR 0.94, 95% CI 0.72 to 1.24). A pilot study with 60 participants used a higher dose of vitamin D3 (4000 IU on alternate days) and found preliminary evidence that this dose probably has no effect on cognitive function over six months.We included data from one trial of zinc and copper supplementation with 1072 participants. There was moderate-certainty evidence of little or no effect on overall cognitive function (MD 0.6 MMSE points, 95% CI -0.19 to 1.39) or on the incidence of cognitive impairment after 5 years to 10 years. A second smaller trial provided no usable data, but reported no cognitive effects of six months of supplementation with zinc gluconate.From one study with 3711 participants, there was low-certainty evidence of no effect of approximately five years of selenium supplementation on the incidence of dementia (HR 0.83, 95% CI 0.61 to 1.13).Finally, we included three trials of complex supplements (combinations of B vitamins, antioxidant vitamins, and minerals) with 6306 participants. From the one trial which assessed overall cognitive function, there was low-certainty evidence of little or no effect on the TICS (MD after a mean of 8.5 years 0.12, 95% CI -0.14 to 0.38). AUTHORS' CONCLUSIONS:We did not find evidence that any vitamin or mineral supplementation strategy for cognitively healthy adults in mid or late life has a meaningful effect on cognitive decline or dementia, although the evidence does not permit definitive conclusions. There were very few data on supplementation starting in midlife (< 60 years); studies designed to assess cognitive outcomes tended to be too short to assess maintenance of cognitive function; longer studies often had other primary outcomes and used cognitive measures which may have lacked sensitivity. The only positive signals of effect came from studies of long-term supplementation with antioxidant vitamins. These may be the most promising for further research.
10.1002/14651858.CD011906.pub2
[Cognitive Function and Calcium. Cerebral calcium oscillation: functional implication toward cognitive functions].
Osanai Makoto
Clinical calcium
Calcium is universal and versatile signal transduction molecule. Intracellular calcium is precisely regulated by various cellular mechanisms, making it possible to contribute to normal neuronal functions. Recently, the relationship between calcium and neuronal functions including cognitive functions has been investigated. This paper reviews normal and abnormal functions of calcium in a perspective of raveling the pathophysiology of neuropsychiatric disorders, such as Alzheimer's disease and Parkinson's disease. And, I introduce the slow calcium oscillation in striatum, which lasted more than 100 s, and discuss the pathophysiological function of the slow calcium oscillation in the neuropsychiatric disorder, especially in Parkinson's disease.
CliCa1502217225
Calcium chloride mimics the effects of acamprosate on cognitive deficits in chronic alcohol-exposed mice.
Psychopharmacology
RATIONALE:Acamprosate (calcium-bis N-acetylhomotaurinate) is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Acamprosate can improve executive functions that are impaired by chronic intermittent ethanol (CIE) exposure. Recent work has suggested that acamprosate's effects on relapse prevention are due to its calcium component, which raises the question whether its pro-cognitive effects are similarly mediated by calcium. OBJECTIVES:This study examined the effects of acamprosate on alcohol-induced behavioral deficits and compared them with the effects of the sodium salt version of N-acetylhomotaurinate or calcium chloride, respectively. METHODS:We exposed mice to alcohol via three cycles of CIE and measured changes in alcohol consumption in a limited-access paradigm. We then compared the effects of acamprosate and calcium chloride (applied subchronically for 3 days during withdrawal) in a battery of cognitive tasks that have been shown to be affected by chronic alcohol exposure. RESULTS:CIE-treated animals showed deficits in attentional set-shifting and deficits in novel object recognition. Alcohol-treated animals showed no impairments in social novelty detection and interaction, or delayed spontaneous alternation. Both acamprosate and calcium chloride ameliorated alcohol-induced cognitive deficits to comparable extents. In contrast, the sodium salt version of N-acetylhomotaurinate did not reverse the cognitive deficits. CONCLUSIONS:These results add evidence to the notion that acamprosate produces its anti-relapse effects through its calcium moiety. Our results also suggest that improved regulation of drug intake by acamprosate after withdrawal might at least in part be related to improved cognitive function.
10.1007/s00213-018-4900-1
Dairy, soy, and calcium consumption and risk of cognitive impairment: the Singapore Chinese Health Study.
Talaei Mohammad,Feng Lei,Yuan Jian-Min,Pan An,Koh Woon-Puay
European journal of nutrition
PURPOSE:It is unclear if midlife consumption of dairy and soy food intake, and their components of calcium and isoflavones (in soy), is related to cognitive impairment in elderly. METHODS:We used baseline data on lifestyle and habitual diet of 16,948 participants collected during their recruitment into the Singapore Chinese Health Study from 1993 to 1998, and data on their cognitive function, measured using a 30-item Singapore modified Mini-Mental State Examination, during follow-up interviews from 2014 to 2016. We used multivariable logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for developing cognitive impairment. RESULTS:Higher dairy intake was associated with a lower risk of cognitive impairment in a dose-dependent manner (P for trend = 0.009). Compared to the lowest quartile of dairy intake, ORs (95% CIs) were 0.93 (0.81-1.07) for the second, 0.88 (0.76-1.01) for the third, and 0.82 (0.72-0.94) for the fourth quartiles of intake. Similar results were found for dairy calcium intake (P for trend = 0.008). However, there was no statistically significant association for intake of soy (OR comparing extreme quartiles 0.99, 95% CI 0.87-1.14, P for trend = 0.92), isoflavones (OR 1.01, 95% CI 0.88-1.15, P for trend = 0.90) or non-dairy calcium (OR 1.06, 95% CI 0.86-1.30, P for trend = 0.81) with risk of cognitive impairment. CONCLUSIONS:Dairy intake at midlife could have a protective association against cognitive impairment that may not be attributed to its calcium content alone, while soy or isoflavone intake was not associated with the cognition of elderly in our study.
10.1007/s00394-019-02010-8
Effects of Bisphosphonates and Calcium plus Vitamin-D Supplements on Cognitive Function in Postmenopausal Osteoporosis§.
Safer Umut,Safer Vildan Binay,Demir Sibel Ozbudak,Yanikoglu Inci
Endocrine, metabolic & immune disorders drug targets
BACKGROUND:Postmenopausal osteoporosis has been linked to accelerated cognitive decline; however, little is known about the effects of medical treatment on cognitive functions. MATERIAL AND METHODS:In this prospective study, we evaluated the effects of bisphosphonate treatment and calcium plus vitamin D supplementation on cognitive functions in 45 women with postmenopausal osteoporosis who were started on medical treatment. The medications included alendronate, zoledronic acid, risedronate, or ibandronic acid along with a low or high dose of calcium plus vitamin D supplements. The cognitive function was assessed by the mini-mental state examination (MMSE) test. All subjects underwent bone mineral density (BMD) measurement via dual-energy X-ray absorptiometry at baseline and at study completion. RESULTS:The mean T-score improved significantly at 1 year, except for neck of the femur area. The mean MMSE score did not change significantly at 12 months (26.40 ± 2.07 vs. 26.48 ± 2.07; p = 0.513), with no difference among bisphosphonates combined with calcium plus vitamin D. Higher dose (1200 mg/800 U/day) of calcium plus vitamin D supplementation tended to have a greater improvement as compared with lower dose (600 mg/400 U/day) (Δ MMSE: 0.11 ± 0.72 vs. -0.14 ± 0.69). CONCLUSIONS:Cognitive functions in the women remained unaltered, whereas bone BMD T-scores were significantly improved at the 12(th) month after the administration of bisphosphonates and calcium plus vitamin D supplements. Higher doses of calcium plus vitamin D supplements were likely to have better cognitive effects as compared with lower doses.
10.2174/1871530316666160330105952
Low intakes of carotene, vitamin B , pantothenate and calcium predict cognitive decline among elderly patients with diabetes mellitus: The Japanese Elderly Diabetes Intervention Trial.
Araki Atsushi,Yoshimura Yukio,Sakurai Takashi,Umegaki Hiroyuki,Kamada Chiemi,Iimuro Satoshi,Ohashi Yasuo,Ito Hideki,
Geriatrics & gerontology international
AIM:The present study aimed to examine whether nutrient intakes predicted cognitive decline among elderly patients with diabetes mellitus. METHODS:This study evaluated data from a 6-year prospective follow up of 237 elderly patients (aged ≥65 years) with diabetes mellitus, and the associations of baseline nutrient intakes with cognitive decline. Cognitive decline was defined as a ≥2-point decrease in the Mini-Mental State Examination (MMSE) score. Intakes of food and nutrients were assessed using a validated food frequency questionnaire, and were compared between patients with cognitive decline and intact cognition. Analysis of covariance and logistic regression analysis were used to compare the changes in the MMSE score during the follow up among intake tertile groups for each nutrient. RESULTS:Compared with men with intact cognition, the men with cognitive decline had lower baseline intakes of calcium, vitamin A, vitamin B , pantothenate, soluble fiber, green vegetables and milk. However, no significant associations between cognitive decline and nutrient intakes were observed among women. After adjusting for age, body mass index, glycated hemoglobin levels, history of severe hypoglycemia, previous stroke and baseline MMSE score, we found that cognitive decline was significantly associated with low intakes of carotene, vitamin B , pantothenate, calcium and green vegetables. Multiple logistic regression analysis showed that intakes of nutrients and green vegetables predicted cognitive decline after adjusting for age, body mass index, glycated hemoglobin levels, baseline MMSE score, and incident stroke during the follow up. CONCLUSIONS:These findings suggest that sufficient intakes of carotene, vitamin B , pantothenate, calcium and vegetables could help prevent cognitive decline among elderly men with diabetes mellitus. Geriatr Gerontol Int 2017; 17: 1168-1175.
10.1111/ggi.12843
Changes in presynaptic calcium signalling accompany age-related deficits in hippocampal LTP and cognitive impairment.
Pereda Daniel,Al-Osta Ibrahim,Okorocha Albert E,Easton Alexander,Hartell Nicholas A
Aging cell
The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long-term potentiation requires stronger stimulation for induction in aged rats and mice and long-term depression becomes more prevalent. An age-dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age-dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T-maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired-pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age-dependent change in the properties or numbers of presynaptic calcium channels.
10.1111/acel.13008
Effects of Vitamin D and Calcium Fortified Yogurts on Gait, Cognitive Performances, and Serum 25-Hydroxyvitamin D Concentrations in Older Community-Dwelling Females: Results from the GAit, MEmory, Dietary and Vitamin D (GAME-D2) Randomized Controlled Trial.
Beauchet Olivier,Launay Cyrille P,Galery Kevin,Vilcocq Christine,Dontot-Payen Flore,Rousseau Brigitte,Benoit Valérie,Allali Gilles
Nutrients
BACKGROUND:Vitamin D fortified food may improve serum vitamin D level, suggesting that the prevention of adverse consequences of hypovitaminosis D is possible with food fortification. The aim of this randomized controlled trial (RCT) was to examine the effects of vitamin D and calcium fortified yogurt on spatiotemporal gait parameters, cognitive performance, handgrip strength, and serum 25OHD levels in healthy older females. METHODS:Forty older community-dwelling females were recruited in a single-blind, randomized, controlled, superiority clinical trial in two parallel groups (20 participants in the intervention group and 20 in the control group) with intent-to-treat. The intervention group took fortified yogurts daily (i.e., 400 UI of vitamin D and 800 mg calcium) for 3 months. The non-fortified yogurts contained similar proteins, carbohydrates and lipids, as well as a lower dose of calcium (300 mg) and no vitamin D supplementation. Spatiotemporal gait parameters (mean value and coefficient of variation) were assessed using a computerized walkway. Handgrip strength was measured with hydraulic dynamometers. Cognitive performances, including global cognitive functioning assessed with the Mini Mental Status Examination (MMSE) were recorded. All the outcomes were assessed at baseline and at the end of follow-up. The primary outcome was the coefficient of variation of stride time. RESULTS:The intervention group maintained its global cognitive performance and serum 25OHD concentrations, whereas these outcomes decreased (i.e., worst performance) in the control group. The changes in the MMSE score ( = 0.022) and serum 25OHD concentrations were different ( ≤ 0.001) with better values reported in the intervention group compared to the control group. There was no significant change in gait parameters ( ≥ 0.518) and handgrip strength ( ≥ 0.600). CONCLUSIONS:Fortified yogurts with vitamin D (i.e., 200 IU) and calcium (i.e., 400 mg) twice a day maintained global cognitive performance and vitamin D status in older females, but not gait performances, signifying that they mainly prevent hypovitaminosis D-related extra-skeletal disorders.
10.3390/nu11122880
Lower Serum Calcium as a Potentially Associated Factor for Conversion of Mild Cognitive Impairment to Early Alzheimer's Disease in the Japanese Alzheimer's Disease Neuroimaging Initiative.
Sato Kenichiro,Mano Tatsuo,Ihara Ryoko,Suzuki Kazushi,Tomita Naoki,Arai Hiroyuki,Ishii Kenji,Senda Michio,Ito Kengo,Ikeuchi Takeshi,Kuwano Ryozo,Matsuda Hiroshi,Iwatsubo Takeshi,Toda Tatsushi,Iwata Atsushi,
Journal of Alzheimer's disease : JAD
BACKGROUND:Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer's disease (AD) remains uncertain. OBJECTIVE:To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study cohort. METHODS:In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from the North American (NA)-ADNI. RESULTS:Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. CONCLUSION:Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information.
10.3233/JAD-181115
Serum calcium levels and neuropsychological performance in depression and matched healthy controls: Reversal of correlation a marker of the aging cognitive clock?
Grützner Thea Marianne,Listunova Lena,Fabian Gregor Amadeus,Kramer Benedikt Alexander,Flach Daniel,Weisbrod Matthias,Roesch-Ely Daniela,Sharma Anuradha
Psychoneuroendocrinology
BACKGROUND:Major depressive disorder (MDD) is associated with cognitive impairment, that might be related to disturbed calcium homeostasis. Calcium-related processes have also been implicated in age related cognitive decline. Since serum calcium and brain interstitial fluids maintain long-term equilibrium under normal physiological states, serum calcium levels could affect neuronal and hence cognitive function. High serum calcium has been associated with cognitive decline in geriatric populations, whereas evidence for MDD and healthy populations is less consistent. METHODS:Differences in neuropsychological (NPS) performance and their relationship with serum calcium (total, ionized, total to ionized ratio) in (partially) remitted MDD patients (n = 59) and healthy controls (HC) (n = 59) individually matched for age, gender and education (age-range 19-60 years) were examined. Modulation of study parameters and their interaction by the factor age was investigated, with subgroups young and old divided at median = 37 years. Participants provided blood samples and completed an extensive NPS test battery. RESULTS:MDD showed significantly poorer NPS performance compared to HC. Serum calcium associated positively with NPS performance in HC and negatively in MDD for entire age-range samples. While younger MDD and HC showed positive NPS-calcium correlations, older MDD and HC exhibited negative NPS-calcium correlations ('correlation reversal'). Age had a significant effect on cognition and ionized calcium and interacted with illness-status, with an exaggerated influence on cognition in MDD compared to HC. CONCLUSIONS:The results place calcium 'correlation reversal' to early middle-age time window, which may be accelerated for MDD and highlight the central role of calcium pathways in normal and pathological cognitive aging.
10.1016/j.psyneuen.2018.03.012