Cognitive ageing and dementia

إِنَّمَا مَثَلُ ٱلۡحَيَوٰةِ ٱلدُّنۡيَا كَمَآءٍ أَنزَلۡنَٰهُ مِنَ ٱلسَّمَآءِ فَٱخۡتَلَطَ بِهِۦ نَبَاتُ ٱلۡأَرۡضِ مِمَّا يَأۡكُلُ ٱلنَّاسُ وَٱلۡأَنۡعَٰمُ حَتَّىٰٓ إِذَآ أَخَذَتِ ٱلۡأَرۡضُ زُخۡرُفَهَا وَٱزَّيَّنَتۡ وَظَنَّ أَهۡلُهَآ أَنَّهُمۡ قَٰدِرُونَ عَلَيۡهَآ أَتَىٰهَآ أَمۡرُنَا لَيۡلًا أَوۡ نَهَارࣰ ا فَجَعَلۡنَٰهَا حَصِيدࣰ ا كَأَن لَّمۡ تَغۡنَ بِٱلۡأَمۡسِۚ كَذَٰلِكَ نُفَصِّلُ ٱلۡأٓيَٰتِ لِقَوۡمࣲ يَتَفَكَّرُونَ

The life of this world is like this: rain that We send down from the sky is absorbed by the plants of the earth, from which humans and animals eat. But when the earth has taken on its finest appearance, and adorns itself, and its people think they have power over it, then the fate We commanded comes to it, by night or by day, and We reduce it to stubble, as if it had not flourished just the day before. This is the way We explain the revelations for those who reflect

أَوۡ يَكُونَ لَكَ بَيۡتࣱ مِّن زُخۡرُفٍ أَوۡ تَرۡقَىٰ فِي ٱلسَّمَآءِ وَلَن نُّؤۡمِنَ لِرُقِيِّكَ حَتَّىٰ تُنَزِّلَ عَلَيۡنَا كِتَٰبࣰ ا نَّقۡرَؤُهُۥۗ قُلۡ سُبۡحَانَ رَبِّي هَلۡ كُنتُ إِلَّا بَشَرࣰ ا رَّسُولࣰ ا

or have a house made of gold; or ascend into the sky- even then, we will not believe in your ascension until you send a real book down for us to read.’ Say, ‘Glory be to my Lord! Am I anything but a mortal, a messenger?’

وَزُخۡرُفࣰ اۚ وَإِن كُلُّ ذَٰلِكَ لَمَّا مَتَٰعُ ٱلۡحَيَوٰةِ ٱلدُّنۡيَاۚ وَٱلۡأٓخِرَةُ عِندَ رَبِّكَ لِلۡمُتَّقِينَ

and golden ornaments. All of these are mere enjoyments of this life; your Lord reserves the next life for those who take heed of Him

وَكَذَٰلِكَ جَعَلۡنَا لِكُلِّ نَبِيٍّ عَدُوࣰّ ا شَيَٰطِينَ ٱلۡإِنسِ وَٱلۡجِنِّ يُوحِي بَعۡضُهُمۡ إِلَىٰ بَعۡضࣲ زُخۡرُفَ ٱلۡقَوۡلِ غُرُورࣰ اۚ وَلَوۡ شَآءَ رَبُّكَ مَا فَعَلُوهُۖ فَذَرۡهُمۡ وَمَا يَفۡتَرُونَ

In the same way We assigned to each prophet an enemy, evil humans and evil jinn. They suggest alluring words to one another in order to deceive- if it had been your Lord’s will, [Prophet], they would not have done this: leave them to their inventions

Thus have We made for every prophet an enemy, satans of jinn and men. When someone's rank is higher, his trial will be more complete. When someone is nearer to the Real and his heart more limpid, his soul will be more captured by the hand of the enemy. Yes, without the grief of tribulation, the story of love cannot be told. Without the venom of trial, the honey of friendship cannot be found. Look at what Adam the Chosen, that sapling honored by the Real and nurtured by hallowing, saw from his enemy Iblis. God says, “Then Satan made them slip therefrom and brought them out from what they were in” [2:36]. And that other elder of the prophets and father of the world's folk, Noah-look at what he saw from his own people. For nine hundred and some years he invited them, and every day they beat him so much that he became unconscious, and they advised his own children to be his enemies. That par

The likeness the description of the life of this world is only as water rain which We send down from the heaven then the plants of the earth mingle with it they mingle because of it attaching themselves one to another whereof mankind eat plants such as wheat and barley and so on and cattle eat of pasture until when the earth has taken on its ornaments its splendour of plants and has adorned itself with flowers izzayyanat ‘adorned itself’ is originally tazayyanat but the tā’ has been substituted with the zāy and assimilated with it and its inhabitants think that they are masters of it fully capable of harvesting its fruits Our command Our decree or Our chastisement comes upon it by night or day and We make it that is its crops as reaped corn like that which has been reaped with sickles as though ka-an is softened in other words read it as ka-annahā the previous day it had not flourished a

or until you come to have a house adorned with gold or ascend into the heaven upon a ladder and even then we will not believe your ascension if you were to ascend into it until you bring down for us therefrom a book in which is confirmed your truthfulness that we may read’. Say to them ‘Glory be to my Lord — this is a statement of amazement — Am I anything but a human a messenger from God?’ in other words I am like all other messengers for they never brought any signs except by God’s leave.

And so We have appointed to every Prophet an enemy just as We have appointed these your enemies and this ‘adūwwan ‘an enemy’ is substituted by the following shayātīn ‘devils’ devils the rebels of mankind and jinn who inspire whisper fine speech to each other the falsehood that is disguised as such fine speech in delusion that is in order to delude them; yet had your Lord willed they would never have done it that mutual inspiration. So leave them let the disbelievers be with what they fabricate of disbelief and otherwise of what has been adorned for them — this was revealed before the command to fight them.

Verily, the parable of the life of the world is as the water which We send down from the sky; so by it arises the intermingled produce of the earth of which men and cattle eat: until when the earth is clad in its adornments and is beautified, and its people think that they have all the powers of disposal over it, Our command reaches it by night or by day and We make it like a clean-mown harvest, as if it had not flourished yesterday! Thus do We explain the Ayat in detail for the people who reflect (24)Allah calls to the Abode of Peace (Paradise) and guides whom He wills to the straight path (25) The Parable of this Life Allah the Almighty has set an example of the similitude of the life of this world, its glitter and the swiftness of its passage, likening it to the plant and vegetation that Allah brings out from the earth. This plant grows from the water that comes down from the sky. T

And they say: "We shall not believe in you, until you cause a spring to gush forth from the earth for us; (90)"Or you have a garden of date palms and grapes, and cause rivers to gush forth in their midst abundantly; (91)"Or you cause the heaven to fall upon us in pieces, as you have pretended, or you bring Allah and the angels before (us) face to face; (92)"Or you have a house of Zukhruf, or you ascend up into the sky, and even then we will put no faith in your ascension until you bring down for us a Book that we would read." Say: "Glorified be my Lord! Am I anything but a man, sent as a Messenger? (93) The Demand of Quraysh for a specific Sign, and the Rejection of that Ibn Jarir recorded from Muhammad bin Ishaq, "An old man from among the people of Egypt who came to us forty-odd years ago told me, from 'Ikrimah, from Ibn 'Abbas, that 'Utbah and Shaybah – the two sons of Rabi'ah, Abu

حَدَّثَنَا عَبْدُ اللَّهِ بْنُ يُوسُفَ، أَخْبَرَنَا مَالِكٌ، عَنْ يَحْيَى بْنِ سَعِيدٍ، عَنْ عَبْدِ الرَّحْمَنِ الأَعْرَجِ، عَنْ عَبْدِ اللَّهِ ابْنِ بُحَيْنَةَ ـ رضى الله عنه ـ أَنَّهُ قَالَ إِنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَامَ مِنِ اثْنَتَيْنِ مِنَ الظُّهْرِ لَمْ يَجْلِسْ بَيْنَهُمَا، فَلَمَّا قَضَى صَلاَتَهُ سَجَدَ سَجْدَتَيْنِ ثُمَّ سَلَّمَ بَعْدَ ذَلِكَ‏.‏

Narrated `Abdullah bin Buhaina:Allah's Messenger (ﷺ) got up after the second rak`a of the Zuhr prayer without sitting in between (the second and the third rak`at). When he finished the prayer he performed two prostrations (of Sahu) and then finished the prayer with Taslim

حَدَّثَنَا أَبُو الْوَلِيدِ، حَدَّثَنَا شُعْبَةُ، عَنِ الْحَكَمِ، عَنْ إِبْرَاهِيمَ، عَنْ عَلْقَمَةَ، عَنْ عَبْدِ اللَّهِ ـ رضى الله عنه ـ أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم صَلَّى الظُّهْرَ خَمْسًا فَقِيلَ لَهُ أَزِيدَ فِي الصَّلاَةِ فَقَالَ ‏ "‏ وَمَا ذَاكَ ‏"‏‏.‏ قَالَ صَلَّيْتَ خَمْسًا‏.‏ فَسَجَدَ سَجْدَتَيْنِ بَعْدَ مَا سَلَّمَ‏.‏

Narrated' `Abdullah:Once Allah's Messenger (ﷺ) offered five rak`at in the Zuhr prayer, and somebody asked him whether there was some increase in the prayer. Allah's Messenger (ﷺ) said, "What is that?" He said, "You have offered five rak`at." So Allah's Messenger (ﷺ) performed two prostrations of Sahu after Taslim

أَخْبَرَنَا عَمْرُو بْنُ عَلِيٍّ، قَالَ حَدَّثَنَا يَحْيَى بْنُ سَعِيدٍ، قَالَ حَدَّثَنَا حَمَّادُ بْنُ زَيْدٍ، قَالَ حَدَّثَنَا غَيْلاَنُ بْنُ جَرِيرٍ، عَنْ مُطَرِّفِ بْنِ عَبْدِ اللَّهِ، قَالَ صَلَّى عَلِيُّ بْنُ أَبِي طَالِبٍ فَكَانَ يُكَبِّرُ فِي كُلِّ خَفْضٍ وَرَفْعٍ يُتِمُّ التَّكْبِيرَ ‏.‏ فَقَالَ عِمْرَانُ بْنُ حُصَيْنٍ لَقَدْ ذَكَّرَنِي هَذَا صَلاَةَ رَسُولِ اللَّهِ صلى الله عليه وسلم ‏.‏

It was narrated that Mutarrif bin 'Abdullah said:"Ali bin Abi Talib prayed, and he said the takbir every time he went down and came up, in all movements of the prayer. 'Imran bin Husain said: 'This reminds me of the prayer of the Messenger of Allah (ﷺ)

أَخْبَرَنَا يَعْقُوبُ بْنُ إِبْرَاهِيمَ الدَّوْرَقِيُّ، وَمُحَمَّدُ بْنُ بَشَّارٍ، - وَاللَّفْظُ لَهُ - قَالاَ حَدَّثَنَا يَحْيَى بْنُ سَعِيدٍ، قَالَ حَدَّثَنَا عَبْدُ الْحَمِيدِ بْنُ جَعْفَرٍ، قَالَ حَدَّثَنِي مُحَمَّدُ بْنُ عَمْرِو بْنِ عَطَاءٍ، عَنْ أَبِي حُمَيْدٍ السَّاعِدِيِّ، قَالَ سَمِعْتُهُ يُحَدِّثُ، قَالَ كَانَ النَّبِيُّ صلى الله عليه وسلم إِذَا قَامَ مِنَ السَّجْدَتَيْنِ كَبَّرَ وَرَفَعَ يَدَيْهِ حَتَّى يُحَاذِيَ بِهِمَا مَنْكِبَيْهِ كَمَا صَنَعَ حِينَ افْتَتَحَ الصَّلاَةَ ‏.‏

It was narrated from Abu Humaid As-Sa'idi that:When the Prophet (ﷺ) stood up following two prostrations, he would say the takbir and raise his hands until they were level with his shoulders, as he had done at the beginning of the prayer

وبيان درجاته وبيان أقسام المخاوف وبيان فضيلة الخوف وبيان الأفضل من الخرف والرجاء وبيان دواء الخوف وبيان معنى سوء الخاتمة وبيان أحوال الخائفين من الأنبياء صلوات الله عليهم والصالحين رحمة الله عليهم ونسأل الله حسن التوفيق بيان حقيقة الخوف

فلا أحسن من هذه النصيحة وهذا الإرشاد والتعليم الذي لو أخذ به الناس لم يضع في الأكثر حق أحد ولم يتمكن المبطل من الجحود والنسيان

قالوا وكيف يظن بالشرع أنه يخفف عن هذا المتعمد المفرط العاصي لله ورسوله بترك الوجوب ويوجبه على المعذور بالنوم أو النسيان

| فصل قال : والذكر : هو التلخص من الغفلة والنسيان والفرق بين الغفلة

وصرح هؤلاء : أن التوكل والدعاء عبودية محضة لا فائدة لهما إلا ذلك ولو ترك العبد التوكل والدعاء ما فاته شيء مما قدر له ومن غلاتهم من يجعل الدعاء بعدم المؤاخذة على الخطإ والنسيان عديم الفائدة إذ هو مضمون الحصول

وأنشدني المنتصر بن بلال الأنصاري % الرفق ممن سيلقى اليمن صاحبه % والخرف منه يكون العنف والزلل % % والحزم أن يتأنى المرء فرصته % والكف عنها إذا ما أمكنت فشل % % والبر لله خير الأمر عاقبة % والله للبر عون ماله مثل % % خير البريه قولا خيرهم عملا % لا يصلح القول حتى يصلح العمل % $

The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer's disease: a meta-analysis.: Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely reco

Sleep disorders increase the risk of dementia, Alzheimer's disease, and cognitive decline: a meta-analysis.: Sleep disorders, particularly insomnia and obstructive sleep apnea, are increasingly implicated as significant contributors to cognitive decline, dementia, and neurodegenerative diseases such as Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID). However, the extent and specificity of these associations remain uncertain. This meta-analysis evaluates the impact of common sleep disorders on the risk of developing dementia and cognitive decline. A comprehensive search of

Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis.: Objective: Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition. Method: The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analy

Dietary Intake, Mediterranean and Nordic Diet Adherence in Alzheimer's Disease and Dementia: A Systematic Review.: Background/objectives: Dementia is not a single disease but an umbrella term that encompasses a range of symptoms, such as memory loss and cognitive impairments, which are severe enough to disrupt daily life. One of the most common forms of dementia is Alzheimer's Disease (AD), a complex neurodegenerative condition influenced by both genetic and environmental factors. Recent research has highlighted diet as a potential modifiable risk factor for AD. Decades of research have explored the role of

Technology-enhanced multi-domain at home continuum of care program with respect to usual care for people with cognitive impairment: the Ability-TelerehABILITation study protocol for a randomized controlled trial.: Background: According to the World Alzheimer Report (Prince, The Global Impact of Dementia: an Analysis of Prevalence, Incidence, Cost and Trends, 2015), 46.8 million people worldwide are nowadays living with dementia. And this number is estimated to approximate 131.5 million by 2050, with an increasing burden on society and families. The lack of medical treatments able to stop or slow down the course of the disease has moved the focus of interest toward the nonpharmacological approach and psych

Physical exercise attenuates cognitive decline and reduces behavioural problems in people with mild cognitive impairment and dementia: a systematic review.: Questions: What is the effect of physical exercise on cognitive decline and behavioural problems in people with mild cognitive impairment (MCI) or dementia? What is the effect of physical exercise on particular domains of cognitive function? How do training protocols and patients' characteristics influence the outcomes? Design: Systematic review and meta-analysis of randomised trials. Participants: People with MCI or dementia as their primary diagnosis. Intervention: Physical exercise. Outcome m

Tea polyphenols protect learning and memory in sleep-deprived mice by promoting AMPA receptor internalization.

Chronic sleep loss caused lots of health problems, also including cognition impairment. Tea is one of the most popular drinks when people stay up late. Nevertheless, the effects of tea on sleep deprivation-induced cognition impairment are still unclear. In the present study, we found 24-h sleep deprivation (S-DEP) increased membrane α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor level through a tumor necrosis factor α (TNFα)-dependent pathway in hippocampi. Blocking elevated TNFα level can protect S-DEP mice from impaired learning ability according to behavioral test. Tea polyphenols, major active compounds in green tea, suppressed TNFα production through downregulating TNFα converting enzyme (TACE) level. Meanwhile, tea polyphenols treatment could ameliorate recognition impairment and anxiety-like behaviors in S-DEP mice. The aforementioned results demonstrate cogni…

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Distinct Polygenic Score Profiles in Schizophrenia Subgroups With Different Trajectories of Cognitive Development.

Objective: Different cognitive development histories in schizophrenia may reflect variation across dimensions of genetic influence. The authors derived and characterized cognitive development trajectory subgroups within a schizophrenia sample and profiled the subgroups across polygenic scores (PGSs) for schizophrenia, cognition, educational attainment, and attention deficit hyperactivity disorder (ADHD). Methods: Demographic, clinical, and genetic data were collected at the National Institute of Mental Health from 540 schizophrenia patients, 247 unaffected siblings, and 844 control subjects. Cognitive trajectory subgroups were derived through cluster analysis using estimates of premorbid and current IQ. PGSs were generated using standard methods. Associations were tested using general linear models and logistic regression. Results: Cluster analyses identified three cognitive trajectory s…

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Long-term effects of stimulant treatment on ADHD symptoms, social-emotional functioning, and cognition.

Background: Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social-emotional functioning or cognition, measured after medication wash-out. Methods: ADHD symptoms, social-emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n =…

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Heart rate variability biofeedback: implications for cognitive and psychiatric effects in older adults.

Objectives: Two decades of heart rate variability (HRV) biofeedback research have focused on adolescent and adult populations with a variety of symptoms and conditions at the exclusion of older adults. This study explores HRV biofeedback as a novel treatment to decrease psychiatric symptoms and improve cognitive functioning in older adults. Methods: Participants enrolled in a three-week intervention that included six 30-min biofeedback sessions. Neuropsychological and psychiatric measures were administered before and after the intervention. Results: Decreases in depression (Cohen's d = 1.02, p < .001), state anxiety (Cohen's d = 0.82, p = .003), and trait anxiety (Cohen's d = 0.84, p = .002) were observed. An increase in attentional skills as measured by the Trail Making Test - Part A was seen (Cohen's d = 1.00, p = .001). Differences in executive skills as measured by the Trial Making T…

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Baicalin mitigates cognitive impairment and protects neurons from microglia-mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF-κB signaling pathway.

Aims: Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti-inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia-induced neuroinflammation and to explore the mechanisms underlying its anti-inflammation effects. Methods: To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin-1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation-mediated neuron apoptosis in vivo and in vitro using Western…

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B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study.

Objectives: Mental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B12, vitamin B6, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders. Design: The Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study. Setting and participants: Community-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012. Measures: Depression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (H…

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Ceasing exercise induces depression-like, anxiety-like, and impaired cognitive-like behaviours and altered hippocampal gene expression.

Background: Regular exercise can reduce depression-, anxiety-, and impaired cognitive-like behaviours, and upregulate hippocampal genes associated with neuroplasticity. However, the effects of ceasing exercise on depression-, anxiety-, and cognitive-like behaviours, and hippocampal gene expression remain unknown. Methods: 12-week-old C57BL/6 mice (n = 12-16/group) were randomised to six months of exercise (exercise (EXC)), four months of exercise then two months of no exercise (exercise-cessation (EC)), or no-exercise control (CONT) until aged nine months. Depression-, anxiety-, and cognitive-like behaviours were tested with the forced swim test, open field and elevated zero maze, Y-maze, and Barnes maze. The expression of 75 hippocampal genes were investigated by high-throughput quantitative polymerase chain reaction (qPCR). Results: Exercise cessation increased depression- and anxiety-…

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Pediatric Perceived Cognitive Functioning: Psychometric Properties and Normative Data of the Dutch Item Bank and Short Form.

Objective: With increasing numbers of children growing up with conditions that are associated with acquired brain injury, efficient neuropsychological screening for cognitive deficits is pivotal. Brief self-report measures concerning daily complaints can play an important role in such screening. We translated and adapted the pediatric perceived cognitive functioning (PedsPCF) self- and parent-report item bank to Dutch. This study presents (1) psychometric properties, (2) a new short form, and (3) normative data for the short form. Methods: A general population sample of children and parents was recruited. Dimensionality of the PedsPCF was assessed using confirmatory factor analyses and exploratory bifactor analyses. Item response theory (IRT) modeling was used to evaluate model fit of the PedsPCF, to identify differential item functioning (DIF), and to select items for the short form. To…

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Executive function and other cognitive deficits are distal risk factors of generalized anxiety disorder 9 years later.

Objective: The cognitive model (Hirsch & Mathews, 2012) and attentional control theory (Eysenck & Derakshan, 2011) postulate that compromised executive function (EF) and other cognitive constructs are negatively linked to increased excessive and uncontrollable worry, the core symptom of generalized anxiety disorder (GAD). However, the prospective link between neuropsychological constructs and GAD are not well understood. Methods: A nationally representative sample of 2605 community-dwelling adults whose average age was 55.20 (s.d. = 11.41, range 33-84; 56.31% females) participated at baseline and 9-year follow-up. Baseline neuropsychological function and symptoms were measured using the Brief Test of Adult Cognition by Telephone and Composite International Diagnostic Interview - Short Form. Multivariate Poisson and negative binomial regression analyses were conducted with 11 baseline cov…

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The protective effect of 20(S)-protopanaxadiol (PPD) against chronic sleep deprivation (CSD)-induced memory impairments in mice.

Sleep deprivation (SD) is associated with oxidative stress that causes learning and memory impairment. 20(S)-Protopanaxadiol (PPD), one of the protopanaxadiol-type saponins, has antioxidant and neuroprotective effect. This study was designed to research the protective effect of PPD against cognitive deficits induced by chronic sleep deprivation (CSD) in mice. The CSD model was induced by subjecting the mice to our self-made Sleep Interruption Apparatus (SIA) continuously for 14 days. The memory enhancing effects of PPD were evaluated by behavioral tests and the related mechanism was further explored by observing the oxidative stress changes in the cortex and hippocampus of mice. The results revealed that PPD (20 and 40 μmol/kg, i.p.) administration significantly improved the cognitive performance of CSD model mice in object location recognition experiment, novel object recognition task a…

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Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments.

Chronic sleep loss/fragmentation prevalent in the current 24/7 society is associated with irreversible consequences on health and overall wellbeing. Various studies have well documented the ill effects of acute sleep loss on cognitive functions of individuals; however, the underlying mechanism behind the chronic sleep loss is yet to be explored. The present study was aimed to investigate whether chronic sleep deprivation (CSD) triggers anxiety-like behaviour and memory decline in male Wistar rats. Rats were sleep deprived by placing them over slowly rotating drum (2 rpm) for 18 h (between 4 pm and 10 am) followed by 6 h of recovery sleep for 21 consecutive days. Post CSD regimen, rats were subjected to behavioural tests such as elevated plus maze (EPM), Novel Object Recognition (NOR) and Rotarod performance test and then sacrificed to remove brain for further molecular studies. The study…

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Difficulty concentrating in generalized anxiety disorder: An evaluation of incremental utility and relationship to worry.

Difficulty concentrating is one of the most common diagnostic criteria across DSM-5 categories, especially within the emotional (mood- and anxiety-related) disorders. A substantial literature has characterized cognitive functioning in emotional disorders using objective (behavioral) computerized cognitive tasks. However, diagnoses are typically formed on the basis of subjective (self-reported; clinician-rated) assessments of symptoms, and little is known about difficulty concentrating as a symptom. These questions are particularly important for generalized anxiety disorder (GAD), which has long been the subject of nosological debates, and for which several theoretical models that suggest a central role for cognitive impairments (including difficulty concentrating) in the maintenance of psychopathology have been proposed. The present study evaluated the incremental utility of difficulty c…

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Smartphones as assistive technology following traumatic brain injury: a preliminary study of what helps and what hinders.

Purpose: Smartphones have great potential as a convenient, multifunction tool to support cognition and independence following traumatic brain injury (TBI). However, there has been limited investigation of their helpful and less helpful aspects for people with TBI. We aimed to investigate patterns of smartphone use amongst individuals with TBI, identify potential barriers to use, and examine the relationships between smartphone use and daily functioning. Method: Twenty-nine participants with TBI and 33 non-injured participants completed the Smartphone Survey, and measures of subjective and objective cognitive functioning, mood, and community integration. Results: Smartphone use was equally common in both groups, and patterns of app use were similar. More participants with TBI than the comparison group listed using their smartphone as a memory aid as its main benefit. Difficulty in learnin…

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Imbalance between TNFα and progranulin contributes to memory impairment and anxiety in sleep-deprived mice.

Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice. S-DEP increased the levels of TNFα but decreased PGRN levels in the hippocampus. The intracerebroventricular (ICV) injection of PGRN or intraperitoneal injection of TNFα synthesis blocker thalidomide (25 mg/kg), prevented the memory impairment and anxiety behaviors induced by S-DEP. PGRN treatment also restor…

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Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).

Aim: Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). Method: A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to dete…

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Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder.

The present study examined the impacts of major depressive disorder (MDD) on visual and prefrontal cortical activity as well as their connectivity during visual working memory updating and related them to the core clinical features of the disorder. Impairment in working memory updating is typically associated with the retention of irrelevant negative information which can lead to persistent depressive mood and abnormal affect. However, performance deficits have been observed in MDD on tasks involving little or no demand on emotion processing, suggesting dysfunctions may also occur at the more basic level of information processing. Yet, it is unclear how various regions in the visual working memory circuit contribute to behavioral changes in MDD. We acquired functional magnetic resonance imaging data from 18 unmedicated participants with MDD and 21 age-matched healthy controls (CTL) while…

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Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced Mouse Memory Impairment Model.

Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory-improving effects in normal mice and scopolamine-induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14-day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homo…

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Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.

Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasi…

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Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment.

Sleep disorders negatively affect cognition and health. Recent evidence has indicated that chromatin remodeling via histone acetylation regulates cognitive function. This study aimed to investigate the possible roles of histone acetylation in sleep deprivation (SD)-induced cognitive impairment. Results of the Morris water maze test showed that 3 days of SD can cause spatial memory impairment in Wistar rats. SD can also decrease histone acetylation levels, increase histone deacetylase 2 (HDAC2) expression, and decrease histone acetyltransferase (CBP) expression. Furthermore, SD can reduce H3 and H4 acetylation levels in the promoters of the brain-derived neurotrophic factor (Bdnf) gene and thus significantly downregulate BDNF expression and impair the activity of key BDNF signaling pathways (pCaMKII, pErk2, and pCREB). However, treatment with the HDAC inhibitor trichostatin A attenuated a…

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Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

Background: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. Methods: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH. Results: Increased hepcidin-25 was found in serum and primarily in astrocytes after ICH. The brain iron efflux, oxidative brain injury, and cognition impairment were improved in Hepc-/- ICH mice but aggravated by the human hepcidin-25 peptide in C57BL/6 ICH mice. Data obtained in in vitro studies showed that increased hepcidin…

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Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin…

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Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

Background: Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results: Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory defi…

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Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat.

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free (GF) mice highlight the extreme impact on brain health that results from life without commensal microbes. However, the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male SpragueDawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, decreased visceral sensitivity and a greate…

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DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition.

Background: Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored. Methods: We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations, including 50 generation 1 individuals hospitalized during the first year of life for moderate to severe protein-energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study. Attention deficits and cognitive performance were evaluated with the Connors Adult Attention Rating Scale and Wechsler Abbreviated Scale of Intelligence. Expression of nutrition-sensitive genes was explored by quantitative reverse transcriptase polymerase chain reaction in rat pr…

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Patient outcomes up to 15 years after stroke: survival, disability, quality of life, cognition and mental health.

Background: The global epidemiological shift of disease burden towards long-term conditions means understanding long-term outcomes of cardiovascular disease is increasingly important. More people are surviving stroke to experience its long-term consequences, but outcomes in people living more >10 years after stroke have not been described in detail. Methods: Data were collected for the population-based South London Stroke Register, with participants followed up annually until death. Outcomes were survival, disability, activity, cognitive impairment, quality of life, depression and anxiety. Findings: Of 2625 people having first-ever stroke, 262 (21%) survived to 15 years. By 15 years, 61% (95% CI 55% to 67%) of the survivors were male, with a median age of stroke onset of 58 years (IQR 48-66). 87% of the 15-year survivors were living at home and 33.8% (26.2% to 42.4%) had mild disability,…

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