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

Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession.

Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathologic accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated tau in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the β-nicotinamide adenine dinucleotide precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling, and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration, and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. β-Nicotinamide adenine dinucleotide biosynthesis, autophagy, a…

matched on Alzheimer Disease (mesh), cognitive decline (text)

Activity dependent degeneration explains hub vulnerability in Alzheimer's disease.

Brain connectivity studies have revealed that highly connected 'hub' regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming …

matched on Alzheimer Disease (mesh), mild cognitive impairment (text)

Resting state fMRI in Alzheimer's disease: beyond the default mode network.

Using resting state (RS) functional magnetic resonance imaging (fMRI), the connectivity patterns of the default mode (DMN), frontoparietal, executive, and salience networks were explored in 13 Alzheimer's disease (AD) patients, 12 amnestic mild cognitive impairment (aMCI) patients, and 13 healthy controls. Compared with controls and aMCI, AD was associated with opposing connectivity effects in the DMN (decreased) and frontal networks (enhanced). The only RS abnormality found in aMCI patients compared with controls was a precuneus connectivity reduction in the DMN. RS fMRI group differences were only partly related to gray matter atrophy. In AD patients, the mean executive network connectivity was positively associated with frontal-executive and language neuropsychological scores. These results suggest that AD is associated with an alteration of large-scale functional brain networks, whic…

matched on Alzheimer Disease (mesh), mild cognitive impairment (text)

Nutritional predictors of cognitive impairment severity in demented elderly patients: the key role of BMI.

Introduction: The body mass index (BMI) is commonly used to assess nutritional status and the Mini Mental State Examination (MMSE) is a validated tool for assessing cognitive status in elderly people. Nutritional and cognitive aspects are closely related in dementia. Objectives: To establish whether BMI predicts cognitive decline in demented patients and whether an "alarm" BMI cut-off exists for declining MMSE scores. Subjects and methods: 82 elderly demented patients underwent clinical, bio-chemical and functional assessment. Design: Transversal study. Results: The mean BMI was 26.08±4.48 kg/m² and the mean MMSE 18.68±5.38. Patients with BMI<25 kg/m² had significantly lower MMSE scores (16.5±5.53 vs 20.38±4.64; p 0.001), fat-free mass (FFM; 27.76±8.99 vs 37.38±10.58 kg; p<0.001), fat-free mass index (FFMI; 11.52±3.03 vs 14.67±2.89 kg/m²; p<0.001), and fat mass (FM; 24.90±6.89 vs 36.86±6…

matched on Dementia (mesh), cognitive decline (text)

Non-stationarity in the "resting brain's" modular architecture.

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functio…

matched on Alzheimer Disease (mesh), mild cognitive impairment (text)

Experiences of day care and collaboration among people with mild dementia.

Aims: The study was designed to assess how a day care programme once a week, for seven weeks, with group collaboration and social and cultural activities was experienced by clients. The aim was to provide some insight into how older adults with mild cognitive impairment perceive and experience day care. Background: As a consequence of social withdrawal, older adults with mild dementia may suffer a loss of meaningful social life and mental stimulus. Person-centred and collaborative day care may provide support to remaining abilities and facilitate for social activities. Little is known about client experiences and whether and how day care gives meaning to everyday life of persons with mild dementia. Design: A qualitative interview study in a narrative content analysis design. Methods: This study involved narrative interviews with nine Norwegian clients, aged 77-88 years of age, living at …

matched on Dementia (mesh), mild cognitive impairment (text)

Longitudinal changes in memory and executive functioning are associated with longitudinal change in instrumental activities of daily living in older adults.

Impaired everyday function is a diagnostic criterion for dementia, and a determinant of healthcare utilization and caregiver burden. Although many previous studies have demonstrated a cross-sectional relationship between cognition (particularly executive functions and memory) and everyday function in older adults, very little is known about longitudinal relationships between these domains. This study examined the association between longitudinal change in episodic memory (MEM) and executive functioning (EXEC) and change in everyday function. Participants were a cognitively heterogeneous group of 100 elderly persons including those with normal cognition, as well as those with mild cognitive impairment and dementia. They were followed for an average of 5 years. Random effects modeling showed that change in both MEM and EXEC were independently associated with rate of change in informant-rat…

matched on Dementia (mesh), mild cognitive impairment (text)

The relationship between caregiver burden, caregivers' perceived health and their sense of coherence in caring for elders with dementia.

Aim: The aim of this study is to examine associations between caregiver burden, perceived health and sense of coherence in family caregivers to persons with dementia living at home. Background: Most of the studies on family caregivers have focused on burden and morbidity. However, the caregiver's sense of coherence and perceived health have not been studied earlier in relation to caregiver burden. Design: A cross-sectional investigation design was used. Methods: Older persons, 2238 subjects, with any form of social services, were invited to an assessment of cognitive capacity. Those who had cognitive decline (255) were invited for a medical examination and 130 persons were diagnosed as having dementia. The family caregivers to persons with dementia answered a questionnaire including a caregiver burden scale, the Nottingham health profile scale, sense of coherence scale and the Euroqol in…

matched on Dementia (mesh), cognitive decline (text)

Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study.

Background: Dementia takes decades to develop, and effective prevention will likely require early intervention. Thus, it is critical to identify biomarkers of preclinical disease, allowing targeting of high-risk subjects for preventive efforts. Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker. Methodology/principal findings: Among 62 participants of the Nurses' Health Study, we conducted neurologic evaluations, including patient and caregiver interviews, physical exam, neurologic exam, and neuropsychologic testing. We also conducted magnetic resonance imaging (MRI) in a sample of 29 of these women. In these preliminary data, after adjustment for numerous health and lifestyle factors, we found that truncated telomeres in peripheral blood leukocytes segregate with preclini…

matched on Dementia (mesh), mild cognitive impairment (text)

Selective changes of resting-state networks in individuals at risk for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n = 16) and patients with amnestic mild cognitive impairment (aMCI) (n = 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity rela…

matched on Alzheimer Disease (mesh), mild cognitive impairment (text)

A case of unusual autobiographical remembering.

This report describes AJ, a woman whose remembering dominates her life. Her memory is "nonstop, uncontrollable, and automatic." AJ spends an excessive amount of time recalling her personal past with considerable accuracy and reliability. If given a date, she can tell you what she was doing and what day of the week it fell on. She differs from other cases of superior memory who use practiced mnemonics to remember vast amounts of personally irrelevant information. We propose the name hyperthymestic syndrome, from the Greek word thymesis meaning remembering, and that AJ is the first reported case.

matched on Memory Disorders (mesh)

Sex-differences in the association of social health and marital status with blood-based immune and neurodegeneration markers in a cohort of community-dwelling older adults.

Background: The immune system has been proposed to play a role in the link between social health and all-cause dementia risk. We explored cross-sectional and longitudinal associations between social health, immune system balance and plasma neurodegeneration markers in community-dwelling older adults, and explored whether the balance between innate and adaptive immunity mediates associations between social health and both cognition and total brain volume. Methods: Social health markers (social support, marital status, loneliness) were measured in the Rotterdam Study between 2002-2008. Immune system cell counts and balance were assessed repeatedly from 2002 to 2016 using white blood-cell-based indices and individual counts (granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)). Plasma neurodegeneration biomarkers (amyloid-β…

matched on Dementia (mesh), Amyloid beta-Peptides (mesh)

Acoustic stimulation during sleep improves cognition and ameliorates Alzheimer's disease pathology in APP/PS1 mice.

Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time [ZT] 0 to ZT 12 each day), the normal sleep and stress exposure…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Modulating heart rate oscillation affects plasma amyloid beta and tau levels in younger and older adults.

Slow paced breathing via heart rate variability (HRV) biofeedback stimulates vagus-nerve pathways that counter noradrenergic stress and arousal pathways that can influence production and clearance of Alzheimer's disease (AD)-related proteins. Thus, we examined whether HRV biofeedback intervention affects plasma Αβ40, Αβ42, total tau (tTau), and phosphorylated tau-181 (pTau-181) levels. We randomized healthy adults (N = 108) to use slow-paced breathing with HRV biofeedback to increase heart rate oscillations (Osc+) or to use personalized strategies with HRV biofeedback to decrease heart rate oscillations (Osc-). They practiced 20-40 min daily. Four weeks of practicing the Osc+ and Osc- conditions produced large effect size differences in change in plasma Aβ40 and Aβ42 levels. The Osc+ condition decreased plasma Αβ while the Osc- condition increased Αβ. Decreases in Αβ were associated with…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy.

Alzheimer's disease (AD) is the most prevalent cause of dementia1. Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therapeutic strategy2,3. Meningeal lymphatic drainage has an important role in the accumulation of Aβ in the brain4, but it is not known whether modulation of meningeal lymphatic function can influence the outcome of immunotherapy in AD. Here we show that ablation of meningeal lymphatic vessels in 5xFAD mice (a mouse model of amyloid deposition that expresses five mutations found in familial AD) worsened the outcome of mice treated with anti-Aβ passive immunotherapy by exacerbating the deposition of Aβ, microgliosis, neurovascular dysfunction, and behavioural deficits. By contrast, therapeutic delivery of vascular endothelial growth factor C improved clearance of Aβ by monoclonal antib…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Effect of Clostridium butyricum against Microglia-Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate.

Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM-gut-brain axis remains unclear. Here, the anti-neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM-gut-brain axis. Methods and results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid-β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ-induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive i…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Space-like 56Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer's-like transgenic mice.

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer's disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was red…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model.

Clearance of amyloid-beta (Aβ) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aβ clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aβ, suggesting that the peripheral approach of removing Aβ from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aβ burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aβ concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by aggregation of toxic forms of amyloid β peptide (Aβ). Treatment strategies have largely been focused on inhibiting the enzymes (β- and γ-secretases) that liberate Aβ from the amyloid precursor protein (APP). While evidence suggests that individuals who exercise regularly are at reduced risk for AD and studies of animal models demonstrate that running can ameliorate brain Aβ pathology and associated cognitive deficits, the underlying mechanisms are unknown. However, considerable evidence suggests that brain-derived neurotrophic factor (BDNF) mediates beneficial effects of exercise on neuroplasticity and cellular stress resistance. Here, we tested the hypothesis that BDNF promotes non-amyloidogenic APP processing. Using a transgenic mouse model of Alzheimer's disease and cultured human neural cells, we d…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity.

It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer's disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who subsequently convert to having abnormal CSF Aβ42. The earliest Aβ accumulation is further associated with hypoconnectivity within the DMN and between the DM…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Rescue of long-range circuit dysfunction in Alzheimer's disease models.

Alzheimer's disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non-rapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. There is increasing evidence that sleep is often impaired in AD, but it is unclear whether this impairment is directly related to amyloid-β (Aβ) pathology. Here we demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of AD amyloidosis. Most notably, our results reveal an Aβ-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding t…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the …

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans.

Age-associated dementia and Alzheimer's disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life: low-AGE (MG(-)), MG-supplemented low-AGE (MG(+)), and regular (Reg) chow. Older MG(+)-fed mice, similar to old Reg controls, developed MS, increased brain amyloid-β42, deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotin…

matched on Dementia (mesh), Amyloid beta-Peptides (mesh)

Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease.

Background and purpose: Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-related behaviour were investigated. Experimental approach: Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age-matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil. Key results: Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperp…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)

Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly.

Background: Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Methods: Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition. Results: Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed s…

matched on Alzheimer Disease (mesh), Amyloid beta-Peptides (mesh)