scholarly journals Effects of Supplementation with Folic Acid and Its Combinations with Other Nutrients on Cognitive Impairment and Alzheimer’s Disease: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2966
Author(s):  
Ana M. Puga ◽  
Mar Ruperto ◽  
Mª de Lourdes Samaniego-Vaesken ◽  
Ana Montero-Bravo ◽  
Teresa Partearroyo ◽  
...  

Cognitive impairment and Alzheimer’s Disease, among other cognitive dysfunctions, has been recognized as a major public health problem. Folic acid is a well-known essential nutrient whose deficiency has been linked to neurocognitive dysfunctions, owing to hyperhomocysteinemia, an independent risk factor for cardio- and cerebrovascular diseases, including cognitive impairment, Alzheimer’s Disease, and vascular dementia. However, to date, there is certain controversy about the efficacy of vitamin supplementation in patients with these pathologies. Therefore, we have reviewed the available dietary intervention studies based on folic acid, either alone or in combination with different vitamins or nutrients into the progression of Alzheimer’s Disease and Cognitive impairment, highlighting the cognition and biochemical markers employed for the evaluation of the disease progression. Undeniably, the compiled information supports the potential benefits of vitamin supplementation in these pathologies, especially relevant to the aging process and quality of life, although more research is urgently needed to confirm these positive findings.

Author(s):  
David Vaquero-Puyuelo ◽  
Concepción De-la-Cámara ◽  
Beatriz Olaya ◽  
Patricia Gracia-García ◽  
Antonio Lobo ◽  
...  

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.


2001 ◽  
Vol 86 (3) ◽  
pp. 313-321 ◽  
Author(s):  
M. González-Gross ◽  
Ascensión Marcos ◽  
Klaus Pietrzik

As the number of older people is growing rapidly worldwide and the fact that elderly people are also apparently living longer, dementia, the most common cause of cognitive impairment is getting to be a greater public health problem. Nutrition plays a role in the ageing process, but there is still a lack of knowledge about nutrition-related risk factors in cognitive impairment. Research in this area has been intensive during the last decade, and results indicate that subclinical deficiency in essential nutrients (antioxidants such as vitamins C, E and β-carotene, vitamin B12, vitamin B6, folate) and nutrition-related disorders, as hypercholesterolaemia, hypertriacylglycerolaemia, hypertension, and diabetes could be some of the nutrition-related risk factors, which can be present for a long time before cognitive impairment becomes evident. Large-scale clinical trials in high-risk populations are needed to determine whether lowering blood homocysteine levels reduces the risk of cognitive impairment and may delay the clinical onset of dementia and perhaps of Alzheimer's disease. A curative treatment of cognitive impairment, especially Alzheimer's disease, is currently impossible. Actual drug therapy, if started early enough, may slow down the progression of the disease. Longitudinal studies are required in order to establish the possible link of nutrient intake – nutritional status with cognitive impairment, and if it is possible, in fact, to inhibit or delay the onset of dementia.


2021 ◽  
Vol 20 (3) ◽  
pp. 2677
Author(s):  
O. V. Zimnitskaya ◽  
E. Yu. Mozheyko ◽  
M. M. Petrova

There is currently no approved list of vascular cognitive impairment biomarkers. The main problem for the practitioner in identifying cognitive impairment in patients is the differential diagnosis of Alzheimer's disease, vascular cognitive impairment, and other diseases, which are much less common. Vascular cognitive impairment includes post-stroke dementia, cognitive dysfunction in cardio-and cerebrovascular diseases. Without etiology identification, it is impossible to prescribe adequate treatment. Another challenge is identifying cognitive impairment before dementia develops. This literature review is devoted to the search and critical analysis of candidates for biomarkers of vascular cognitive impairment and the establishment of markers of moderate cognitive dysfunction. The papers were searched for in the Web of Science and PubMed databases. A list of cerebrospinal fluid, plasma, serum and genetic biomarkers was made, allowing for differential diagnosis between vascular impairment and Alzheimer's disease. The markers of moderate cognitive dysfunction, which make it possible to identify cognitive impairment at the pre-dementia stage, were also identified.


Author(s):  
A.P. Porsteinsson ◽  
E.D. Clark

Alzheimer’s disease (AD) remains one of our greatest unmet medical needs, without any approved disease-modifying therapies. The emotional and financial burden of AD is enormous and predicted to grow exponentially with increasing median population age, posing a major public health problem. The potential to prevent or improve cognitive decline due to AD has important implications. There are medications currently approved for symptomatic treatment of AD, but they have limited clinical benefits and do not change the ultimate trajectory of the disease. The need to find effective treatments for AD that can prevent, slow, arrest, or even reverse the disease is ever more urgent and interventions that delay the symptomatic onset of AD would have a major public health impact (1).


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 228
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Guoping Peng ◽  
Ping Liu ◽  
...  

Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ying Chua ◽  
Yuek Ling Chai ◽  
Wee Siong Chew ◽  
Joyce R. Chong ◽  
Hui Li Ang ◽  
...  

Abstract Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. Methods We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Results Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Conclusion Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.


2015 ◽  
Vol 10 (2) ◽  
pp. 195
Author(s):  
Ignacio J Previgliano ◽  
Bader Andres ◽  
Pawel J Ciesielczyk ◽  
◽  
◽  
...  

Cognitive impairment after critical illness (CIACI) is a frequent consequence of serious disease or injury that has been reported in as many as 66 % of patients, 3 months after an illness requiring intensive care unit hospitalisation. The condition has been recognised only within the past 15 years and its pathological mechanisms are, as yet, incompletely understood. The neurological changes and cellular and inflammatory processes of CIACI overlap with those of stroke, traumatic brain injury and neurodegenerative disorders. Patients also show brain atrophy, which worsens with the duration of intensive care unit stay. Risk factors associated with CIACI include depression, biomarkers of Alzheimer’s disease (e.g. apolipoprotein E), delirium, exposure to some drugs (e.g. fentanyl, morphine and propofol) and intubation. Current strategies to prevent or treat CIACI include treatments to reduce agitation and delirium and physical and mental rehabilitation including cognitive therapy. Many brain diseases and injuries affect the functioning of the neurovascular unit (NVU), which constitutes the key cellular building block of the blood–brain barrier (BBB). CIACI is believed to affect the integrity of the NVU and it is among the potential targets for therapy. Neurotrophic factors (NTFs), such as brain-derived neurotrophic factor (BDNF) are known to play an important role in neurogenesis, maintenance of NVU structure and neuronal repair after disease and injury. This led to the development of strategies including the NTF-preparation (Cerebrolysin®), which is effective as a post-stroke therapy and has potential in the treatment of Alzheimer’s disease and brain injury as well as CIACI. There are currently no proven treatments for CIACI; improved understanding of the condition and further evaluation of NTFs may lead to effective treatments, which are vital to tackle this increasingly serious public health problem.


2000 ◽  
Vol 2 (2) ◽  
pp. 91-100 ◽  

Alzheimer's disease is one of the most devastating brain disorders of elderly humans. It is an undertreated and under-recognized disease that is becoming a major public health problem. The last decade has witnessed a steadily increasing effort directed at discovering the etiology of the disease and developing pharmacological treatment. Recent developments include improved clinical diagnostic guidelines and improved treatment of both cognitive disturbance and behavioral problems. Symptomatic treatment mainly focusing on cholinergic therapy has been clinically evaluated by randomized, double-blind, placebo-controlled, parallel-group studies measuring performance-based tests of cognitive function, activities of daily living, and behavior. Cholinesterase inhibitors, including donepezil, tacrine, rivastigmine, and galantamine are the recommended treatment of cognitive disturbance in patients with Alzheimer's disease. The role of estrogen replacement, anti-inflammatory agents, and antioxidants is controversial and needs further study. Antidepressants, antipsychotics, mood stabilizers, anxiolytics, and hypnotics are used for the treatment of behavioral disturbance. Future directions in the research and treatment of patients with Alzheimer's disease include: applying functional brain imaging techniques in early diagnosis and evaluation of treatment efficacy; development of new classes of medications working on different neurotransmitter systems (cholinergic, glutamatergic, etc), both for the treatment of the cognitive deficit and the treatment of the behavioral disturbances; and developing preventive methods (amyloid p-peptide immunizations and inhibitors of β-secretase and γ-secretase).


1996 ◽  
Vol 8 (S1) ◽  
pp. 25-30 ◽  
Author(s):  
Jeffrey L. Cummings

Dementia is a major public health problem in the United States and the world, requiring the expenditure of enormous economic and human resources. Dementia is common in the elderly, and, as the size of the aged population increases, the number of dementia victims will rise. Many dementias are fatal, producing the gradual erosion of intellectual abilities and eventual death of the patient. Demands made on family members and caregivers of dementia patients are extraordinary and often result in their emotional and financial exhaustion. Although basic science efforts are devoted to finding a cure for Alzheimer's disease (AD) and other dementing illnesses, there is an urgent need for research that has immediate applicability to the 4 million current dementia patients.


2021 ◽  
Vol 22 (3) ◽  
pp. 1273
Author(s):  
Rola A. Bekdash

Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the etiology of Alzheimer’s disease. Cholinergic neurons are widely distributed in brain regions that play a role in cognitive functions and normal cholinergic signaling related to learning and memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) is the main noradrenergic nucleus that projects and supplies norepinephrine to different brain regions. Norepinephrine has been shown to be neuroprotective against neurodegeneration and plays a role in behavior and cognition. Cholinergic and adrenergic signaling are dysregulated in Alzheimer’s disease. The degeneration of cholinergic neurons in nucleus basalis of Meynert in the basal forebrain and the degeneration of LC-NE neurons were reported in Alzheimer’s disease. The aim of this review is to describe current literature on the role of the cholinergic system and the adrenergic system (LC-NE) in the pathology of Alzheimer’s disease and potential therapeutic implications.


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