检索问题
老年痴呆可以逆转吗
答案是：这取决于“痴呆”的真正原因是什么，以及发现得有多早。简单来说，很多被误认为是“老年痴呆”的情况是完全可以逆转的；即使是真正的阿尔茨海默病（Alzheimer's disease），如果处于早期阶段，通过精准的综合干预，也有逆转认知能力下降的科学证据。
如果你或你的家人正面临记忆力减退的困扰，请不要立刻觉得“天塌了”或者“没救了”。现在的科学研究已经不再把所有认知障碍都看作是一条通往黑暗的单行道。
为了让你更清楚地了解情况，我们需要把这个问题像剥洋葱一样剥开来看。
一、 许多“痴呆”其实是“假”的，完全可以治好
很多人一看到老人记性不好、反应变慢，就觉得是得了绝症。但实际上，有很多身体疾病会伪装成“痴呆”的样子。在医学上，这被称为“可逆性痴呆”（Reversible Dementias）。如果把背后的病根治好了，脑子自然就清醒了。
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甲状腺在“捣乱”
- 身体的油门坏了： 甲状腺就像身体的油门踏板，控制着新陈代谢的速度。如果甲状腺激素分泌太少（成人甲状腺功能减退症），身体这部车就会开得特别慢，脑子也会像“生锈”了一样转不动。
- 科学证据： 研究发现，甲状腺功能减退不仅让脑子变慢，还会真的改变大脑的结构，损伤海马体（Hippocampus，这是大脑里负责像U盘一样存储记忆的关键部位）和前额叶皮层（Prefrontal Cortex，负责做决策和思考的大脑指挥官）。好消息是，如果能及时补充甲状腺激素，这种认知损伤是可以修复的，但如果拖得太久，可能会造成永久性伤害 。
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睡眠问题导致的“大脑缺氧”
- 打呼噜的代价： 很多老人睡觉打呼噜震天响，甚至呼吸暂停，这叫阻塞性睡眠呼吸暂停（OSA）。这不仅仅是吵，更是在让大脑慢性缺氧。
- 科学证据： 缺氧会导致大脑里堆积垃圾蛋白，还会引发炎症。研究表明，这类患者如果接受正压呼吸机（CPAP）治疗，让大脑晚上喝饱氧气，他们的记忆力、注意力和执行能力都能得到改善 。失眠和睡眠不足本身也是大脑变傻的风险因素，但它们通常是可以调整的 。
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情绪在作祟（假性痴呆）
- 严重的抑郁症在老年人身上，表现得有时候跟痴呆一模一样：反应迟钝、不想说话、记不住事。但这其实是情绪生病了，而不是大脑坏死了。通过抗抑郁治疗，这种认知状态是可以恢复的 。
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药物副作用
- 老年人常吃很多药，有些药物（比如某些安眠药、抗过敏药）的副作用就是让人迷糊。调整药物清单后，这种迷糊往往就会消失 。
二、 抓住“黄金窗口期”：早期阶段是可以回头的
在完全变成“痴呆”之前，大脑通常会经历一个中间状态，叫轻度认知障碍（MCI）。这时候，老人可能只是觉得“脑子不好使了”，但还能照顾自己。还有一个概念叫认知衰弱（Cognitive Frailty），就是人又虚弱，脑子又慢。
这个阶段是逆转病情的最佳时机！
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力量训练比吃药还管用
- 你可能觉得老人该静养，但科学告诉你：要撸铁！
- 具体数据： 一项针对认知衰弱老人的研究发现，进行为期 4个月 的高速抗阻训练（也就是举哑铃、拉弹力带这种练肌肉的运动），老人们的记忆力、处理速度和执行功能都显著提高了！而且身体也变得更有劲儿了。这就是通过运动逆转了大脑的颓势 。
- 现状： 在中国老年人中，这种“身心双虚”的认知衰弱患病率高达 18.9%，但其中很大一部分（约20%）属于可逆性认知衰弱。只要动起来，就能把很多老人从悬崖边拉回来 。
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生活方式的全面突击
- 虽然目前没有一种神药能治好MCI，但改变生活方式（饮食、锻炼、脑力游戏）已经被证明是有效的 。一项名为COGITO的研究正在通过数字化手段，让老人在家里结合运动和认知训练（比如一边骑车一边做算术），目的就是为了逆转这种早期的衰退 。
三、 挑战“不可治愈”：阿尔茨海默病的新希望
这是大家最关心的部分。传统观念认为，一旦确诊阿尔茨海默病（AD），就是判了死刑，只能眼睁睁看着恶化。但最新的前沿研究正在打破这个魔咒。
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给大脑补36个“漏洞”
- 新观点： 阿尔茨海默病不是由单一原因引起的，它更像是一个屋顶漏雨的房子，可能有36个漏洞（比如炎症、营养缺乏、毒素、胰岛素抵抗等）。只堵住一个洞（只吃一种药）是没用的，必须把所有洞都堵上。
- 惊人的逆转案例： 美国加州大学洛杉矶分校的研究团队使用了一种叫 MEND 的个性化治疗方案。他们不是只给药，而是全面调整患者的代谢：
- 吃什么： 严格的饮食调整（低糖、抗炎）。
- 睡多久： 保证每晚8小时睡眠。
- 补什么： 根据血液检测补充维生素B12、维生素D、鱼油等。
- 做什么： 每天运动，减轻压力。
- 数据说话： 在一项针对10名早期阿尔茨海默病或轻度认知障碍患者的研究中，9名患者 的症状得到了逆转！其中6名本来已经无法工作或工作很吃力的人，后来都能重返工作岗位，而且这种改善持续了很久 。这证明了，通过系统性地优化身体代谢，早期的阿尔茨海默病是可以逆转的。
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未来的黑科技：送“能量工厂”进大脑
- 有些认知障碍是化疗药物引起的（俗称“化疗脑”）。科学家发现，这是因为脑细胞里的线粒体（Mitochondria，细胞里的微型发电厂，负责给细胞提供能量）坏了。
- 实验进展： 研究人员尝试从健康的干细胞里提取线粒体，然后通过鼻子滴入小鼠体内。结果发现，这些健康的“发电厂”真的进入了小鼠大脑，修好了受损的神经，逆转了认知缺陷 。虽然这还在动物实验阶段，但展示了未来无限的可能性。
四、 总结与建议
不要把“老糊涂”当成自然现象，也不要因为确诊了就放弃治疗。
- 第一步，去医院“排雷”： 如果发现记忆力下降，先去医院做全面检查，排除甲状腺问题、睡眠呼吸暂停、药物副作用、维生素缺乏等可逆原因。如果找到这些病因，治好它们，脑子可能就清楚了 。
- 早期干预是关键： 现在的研究发现，单一的药物可能不管用，但是“多管齐下”的方案（饮食+运动+睡眠+营养补充+减压）在早期阶段具有强大的逆转潜力 。
- 动起来： 尤其是力量训练（练肌肉），这对大脑的修复作用比我们想象的要大得多 。
所以，结论是充满希望的：很多看似痴呆的情况是可以逆转的，即使是真正的阿尔茨海默病，在早期通过极度自律和科学的综合管理，也有很大机会实现逆转，重回正常生活。
References
1Mild Cognitive Impairment.PubMed
Angela M Sanford
Clin Geriatr Med. 2017 Aug;33(3):325-337. doi: 10.1016/j.cger.2017.02.005. Epub 2017 May 17.
Mild cognitive impairment (MCI) occurs along a continuum from normal cognition to dementia. A roadblock to earlier diagnosis and potential treatment is the lack of consistency with screening for MCI. Universal screening would be ideal, but is limited. Once a diagnosis of MCI is made, it is important for the clinician to evaluate for reversible causes. At present time, there are no pharmacologic treatments proven to slow or cure progression of MCI to dementia; nonetheless, there is evidence that lifestyle modifications including diet, exercise, and cognitive stimulation may be effective.
2Mild Cognitive Impairment in Geriatrics.PubMed
Eric G Tangalos, Ronald C Petersen
Clin Geriatr Med. 2018 Nov;34(4):563-589. doi: 10.1016/j.cger.2018.06.005. Epub 2018 Aug 21.
Mild cognitive impairment remains a clinical diagnosis, aided by history, neurologic examination, screening mental status examination, and secondary testing. It can be difficult to distinguish from normal aging without understanding a patient's prior level of intellectual function and new complaint. Geriatricians encounter patients with mild cognitive impairment in all long-term care settings. Making the diagnosis allows patients and their families to understand limits and develop strategies to maximize function. Etiologies associated with mild cognitive impairment include degenerative and vascular processes, psychiatric causes, and comorbid medical conditions. Treatable medical conditions may also present as mild cognitive impairment and have reversible outcomes.
3Reversal of cognitive decline in Alzheimer's disease.PubMed
Dale E Bredesen, Edwin C Amos, Jonathan Canick, et al.
Aging (Albany NY). 2016 Jun;8(6):1250-8. doi: 10.18632/aging.100981.
Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.
4Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.PubMed
Yaping Lu, Xiang Chen, Xiuxiu Liu, et al.
Autophagy. 2023 Jun;19(6):1803-1820. doi: 10.1080/15548627.2022.2162244. Epub 2023 Jan 1.
Cognitive impairment caused by systemic chemotherapy is a critical question that perplexes the effective implementation of clinical treatment, but related molecular events are poorly understood. Herein, we show that bortezomib exposure leads to microglia activation and cognitive impairment, this occurs along with decreased nuclear translocation of TFEB (transcription factor EB), which is linked to macroautophagy/autophagy disorder, STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL23A (interleukin 23 subunit alpha) expression. Pharmacological enhancement of TFEB nuclear translocation by digoxin restores lysosomal function and reduces STAT3-dependent endothelial IL23A secretion. As a consequence, we found that brain endothelial-specific ablation of ameliorated both microglia activation and cognitive dysfunction. Thus, the endothelial TFEB-STAT3-IL23A axis in the brain represents a critical cellular event for initiating bortezomib-mediated aberrant microglial activation and synapse engulfment. Our results suggest the reversal of TFEB nuclear translocation may provide a novel therapeutic approach to prevent symptoms of cognitive dysfunction during clinical use of bortezomib. AAV: adeno-associated virus; BBB: blood-brain barrier; BTZ: bortezomib; DG: digoxin; DGs: dentate gyrus; DLG4/PSD95: discs large MAGUK scaffold protein 4; HBMECs: human brain microvascular endothelial cells; HP: hippocampus; IL23A: interleukin 23 subunit alpha; MBVECs: mouse brain vascular endothelial cells; mPFC: medial prefrontal cortex; NORT: novel object recognition test; OLT: object location test; PLX5622: 6-fluoro-N-([5-fluoro-2-methoxypyridin-3-yl]methyl)-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3- yl)methyl; PPP3/calcineurin: protein phosphatase 3; SBEs: STAT3 binding elements; shRNA: small hairpin RNA; SLC17A7/VGLUT1: solute carrier family 17 member 7; SLC32A1/VGAT: solute carrier family 32 member 1; STAT3: signal transducer and activator of transcription 3, TFEB: transcription factor EB; Ub: ubiquitin.
5Role of Cognitive Frailty in Older Adults With Cardiovascular Disease.PubMed
Naila Ijaz, Yasser Jamil, Charles H Brown, et al.
J Am Heart Assoc. 2024 Feb 20;13(4):e033594. doi: 10.1161/JAHA.123.033594. Epub 2024 Feb 14.
As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.
6Effects of Resistance Exercise Training on Cognitive Function and Physical Performance in Cognitive Frailty: A Randomized Controlled Trial.PubMed
D H Yoon, J-Y Lee, W Song
J Nutr Health Aging. 2018;22(8):944-951. doi: 10.1007/s12603-018-1090-9.
BACKGROUND: Cognitive frailty is defined as the presence of both physical frailty and cognitive impairment (clinical dementia rating score = 0.5), in the absence of dementia. It is characterized by concurrent physical frailty and potentially reversible cognitive impairment. In this study, we sought to elucidate the effects of high-speed resistance exercise training on cognitive function and physical performance in older adults with cognitive frailty. METHODS: We conducted a parallel-group, randomized controlled trial involving community-living older adults with cognitive frailty. The participants' mean age was 73.9 (± 4.3 SD) years, and 69.8% (n=30) were female. Two different 4-month interventions included high-speed resistance exercise training group (n=22) and a control group (balance and band stretching, n=23). Frailty score, cognitive function (memory, processing speed, cognitive flexibility, working memory, executive function), physical function (SPPB, TUG, gait speed), and muscle strength (grip strength, knee extension strength) were assessed at baseline, 8 weeks, and 16 weeks. RESULTS: Statistical analysis showed that exercise improved performance significantly in the tests for cognitive function (processing speed and executive function, both p < 0.05), physical function (SPPB, TUG, gait speed, both p < 0.05), and muscle strength (grip strength, knee extension strength, both p < 0.05). However, no significant changes in frailty score were observed between intervention and either control group (p < 0.05). CONCLUSION: In conclusion, our findings indicate that high-speed resistance exercise training approaches are effective in improving cognitive function and physical performance in older adults with cognitive frailty. This study shows that it is feasible to identify older adults with cognitive frailty in the community and primary care setting for effective intervention to reduce their level of frailty and cognitive impairment.
7Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer's Disease and MCI: A Review.PubMed
Rammohan V Rao, Kaavya G Subramaniam, Julie Gregory, et al.
Int J Mol Sci. 2023 Jan 14;24(2):1659. doi: 10.3390/ijms24021659.
Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in overall cognitive function. Usually manifesting in individuals over the age of 60, this is the most prevalent type of dementia and remains the fifth leading cause of death among Americans aged 65 and older. While the development of effective treatment and prevention for AD is a major healthcare goal, unfortunately, therapeutic approaches to date have yet to find a treatment plan that produces long-term cognitive improvement. Drugs that may be able to slow down the progression rate of AD are being introduced to the market; however, there has been no previous solution for preventing or reversing the disease-associated cognitive decline. Recent studies have identified several factors that contribute to the progression and severity of the disease: diet, lifestyle, stress, sleep, nutrient deficiencies, mental health, socialization, and toxins. Thus, increasing evidence supports dietary and other lifestyle changes as potentially effective ways to prevent, slow, or reverse AD progression. Studies also have demonstrated that a personalized, multi-therapeutic approach is needed to improve metabolic abnormalities and AD-associated cognitive decline. These studies suggest the effects of abnormalities, such as insulin resistance, chronic inflammation, hypovitaminosis D, hormonal deficiencies, and hyperhomocysteinemia, in the AD process. Therefore a personalized, multi-therapeutic program based on an individual's genetics and biochemistry may be preferable over a single-drug/mono-therapeutic approach. This article reviews these multi-therapeutic strategies that identify and attenuate all the risk factors specific to each affected individual. This article systematically reviews studies that have incorporated multiple strategies that target numerous factors simultaneously to reverse or treat cognitive decline. We included high-quality clinical trials and observational studies that focused on the cognitive effects of programs comprising lifestyle, physical, and mental activity, as well as nutritional aspects. Articles from PubMed Central, Scopus, and Google Scholar databases were collected, and abstracts were reviewed for relevance to the subject matter. Epidemiological, pathological, toxicological, genetic, and biochemical studies have all concluded that AD represents a complex network insufficiency. The research studies explored in this manuscript confirm the need for a multifactorial approach to target the various risk factors of AD. A single-drug approach may delay the progression of memory loss but, to date, has not prevented or reversed it. Diet, physical activity, sleep, stress, and environment all contribute to the progression of the disease, and, therefore, a multi-factorial optimization of network support and function offers a rational therapeutic strategy. Thus, a multi-therapeutic program that simultaneously targets multiple factors underlying the AD network may be more effective than a mono-therapeutic approach.
8Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice.PubMed
Jun Mukai, Enrico Cannavò, Gregg W Crabtree, et al.
Neuron. 2019 Nov 6;104(3):471-487.e12. doi: 10.1016/j.neuron.2019.09.014. Epub 2019 Oct 9.
SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.
9Reversible Dementias.PubMed
Milta O Little
Clin Geriatr Med. 2018 Nov;34(4):537-562. doi: 10.1016/j.cger.2018.07.001. Epub 2018 Aug 28.
As the worldwide prevalence of dementia increases, there is a greater and more urgent need for all health care providers to understand how to evaluate and manage cognitive impairment. Many people presenting with a dementing illness have one or more reversible underlying conditions that worsen prognosis and, if treated, can improve cognitive function. This article reviews the major potentially reversible dementias, including the basic workup and management of each condition.
10Reversal of cognitive decline: a novel therapeutic program.PubMed
Dale E Bredesen
Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690.
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.
11Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits.PubMed
Jenolyn F Alexander, Alexandre V Seua, Luis D Arroyo, et al.
Theranostics. 2021 Jan 1;11(7):3109-3130. doi: 10.7150/thno.53474. eCollection 2021.
Up to seventy-five percent of patients treated for cancer suffer from cognitive deficits which can persist for months to decades, severely impairing quality of life. Although the number of cancer survivors is increasing tremendously, no efficacious interventions exist. Cisplatin, most commonly employed for solid tumors, leads to cognitive impairment including deficits in memory and executive functioning. We recently proposed deficient neuronal mitochondrial function as its underlying mechanism. We hypothesized nasal administration of mitochondria isolated from human mesenchymal stem cells to mice, can reverse cisplatin-induced cognitive deficits. Puzzle box, novel object place recognition and Y-maze tests were used to assess the cognitive function of mice. Immunofluorescence and high-resolution confocal microscopy were employed to trace the nasally delivered mitochondria and evaluate their effect on synaptic loss. Black Gold II immunostaining was used to determine myelin integrity. Transmission electron microscopy helped determine mitochondrial and membrane integrity of brain synaptosomes. RNA-sequencing was performed to analyse the hippocampal transcriptome. Two nasal administrations of mitochondria isolated from human mesenchymal stem cells to mice, restored executive functioning, working and spatial memory. Confocal imaging revealed nasally delivered mitochondria rapidly arrived in the meninges where they were readily internalized by macrophages. The administered mitochondria also accessed the rostral migratory stream and various other brain regions including the hippocampus where they colocalized with GFAP cells. The restoration of cognitive function was associated with structural repair of myelin in the cingulate cortex and synaptic loss in the hippocampus. Nasal mitochondrial donation also reversed the underlying synaptosomal mitochondrial defects. Moreover, transcriptome analysis by RNA-sequencing showed reversal of cisplatin-induced changes in the expression of about seven hundred genes in the hippocampus. Pathway analysis identified Nrf2-mediated response as the top canonical pathway. Our results provide key evidence on the therapeutic potential of isolated mitochondria - restoring both brain structure and function, their capability to enter brain meninges and parenchyma upon nasal delivery and undergo rapid cellular internalization and alter the hippocampal transcriptome. Our data identify nasal administration of mitochondria as an effective strategy for reversing chemotherapy-induced cognitive deficits and restoring brain health, providing promise for the growing population of both adult and pediatric cancer survivors.
12Effect of home-based and remotely supervised combined exercise and cognitive intervention on older adults with mild cognitive impairment (COGITO): study protocol for a randomised controlled trial.PubMed
Chenlu Hong, TakChing Tai, Jianwei Zhou, et al.
BMJ Open. 2024 Aug 6;14(8):e081122. doi: 10.1136/bmjopen-2023-081122.
INTRODUCTION: Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and dementia and poses a serious threat to public health worldwide; however, it might be reversible, representing the best opportunity for secondary prevention against serious cognitive impairment. As a non-pharmacological intervention for those patients, interventions that combine physical exercise and cognitive training, whether delivered simultaneously or sequentially, may have superior effects on various cognitive domains, including global cognition, memory, executive function and attention. The supportive evidence remains incomplete. This study aims to assess the effectiveness of a combined exercise and cognitive intervention in Chinese older adults with mild cognitive impairment (COGITO), empowered by digital therapy and guided by the Health Action Process Model and the Theory of Planned Behaviour (HAPA-TPB theory) in a home-based setting. METHODS AND ANALYSIS: This study is a randomised controlled, assessor-blinded multi-centre study. Four parallel groups will include a total of 160 patients, receiving either a combined exercise and cognitive intervention, an isolated exercise intervention, an isolated cognitive intervention or only health education. These interventions will be conducted at least twice a week for 50 min each session, over 3 months. All interventions will be delivered at home and remotely monitored through RehabApp and Mini-programme, along with an arm-worn heart rate telemetry device. Specifically, supervisors will receive participants' real-time training diaries, heart rates or other online monitoring data and then provide weekly telephone calls and monthly home visits to encourage participants to complete their tasks and address any difficulties based on their training information. Eligible participants are community-dwelling patients with no regular exercise habit and diagnosed with MCI. The primary outcome is cognitive function assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and Community Screening Instrument for Dementia (CSI-D), with baseline and three follow-up assessments. Secondary outcomes include quality of life, physical fitness, sleep quality, intrinsic capacity, frailty, social support, adherence, cost-effectiveness and cost-benefit. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Peking University. Research findings will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073900.
13Obstructive Sleep Apnea: Cognitive Outcomes.PubMed
Arpan Patel, Derek J Chong
Clin Geriatr Med. 2021 Aug;37(3):457-467. doi: 10.1016/j.cger.2021.04.007.
There is a strong association between obstructive sleep apnea (OSA) and cognitive dysfunction. Executive function, attention, verbal/visual long-term memory, visuospatial/constructional ability, and information processing are more likely to be affected, whereas language, psychomotor function, and short-term memory are less likely to be affected. Increased accumulation of Aß-amyloid in the brain, episodic hypoxemia, oxidative stress, vascular inflammation, and systemic comorbidities may contribute to the pathogenesis. Patients with OSA should have cognitive screening or formal testing, and patients with cognitive decline should have testing for OSA. Treatment with continuous positive airway pressure may improve cognitive symptoms in the patient with OSA.
14[Sleep disorders].PubMed
Hirokuni Tagaya, Norio Murayama, Yuko Hakamata
Nihon Rinsho. 2014 Apr;72(4):739-43.
Some sleep disorders and sleep problems are reported as risk of dementia. It is reported that 50-80% of idiopathic REM sleep behavior had a later conversion to a synucleinopathy, thus this parasomnia is regarded as early marker of Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Obstructive sleep apnea syndrome causes reversible decline of cognitive functions in children and adults, and it increases the risk of dementia and mild cognitive impairment in elderly women. A decrease of amplitude of circadian activity rhythm and habitual long sleep duration (> or = 9 hours) are reported to increase the risk of dementia in elderly people. Some reports indicate that hypnotic use may be a risk factor of dementia. However, it is not cleared whether insomnia itself related with dementia or not, since no study evaluated the risk of insomnia without hypnotic treatment.
15[Rapidly progressive dementia].PubMed
N G Dudchenko, E E Vasenina
Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(9. Vyp. 2):78-84. doi: 10.17116/jnevro201911909278.
Accurate establishment of the etiology of rapidly progressive dementia is a difficult but very important task, since a number of diseases and conditions that can cause cognitive decline are potentially curable and can be completely reversible with proper diagnosis and timely treatment. While a delay in treatment can lead to severe residual deficiency or death. The article provides current data on the etiology, pathogenesis, clinical presentations, diagnosis and treatment of major diseases and pathological conditions that may cause rapidly progressive dementia.
16Approach to the forgetful patient.PubMed
Peng Soon Yoon, Chun How Ooi, Choon How How
Singapore Med J. 2018 Mar;59(3):121-125. doi: 10.11622/smedj.2018026.
Singapore has an ageing population with a projected 53,000 people aged ≥ 60 years living with dementia by 2020. Primary care doctors have the opportunity to initiate early work-up for reversible causes of cognitive dysfunction, allowing identification of comorbidities and discussion of medical therapy options. Early diagnosis confers the sick role on the patient, which allays frustration and explains events and behaviour that may have strained relationships with family and friends. The patient can be encouraged to plan for future health and personal care options with a Lasting Power of Attorney and/or Advance Care Planning. Objective cognitive tests (e.g. abbreviated mental test and Mini-Mental State Examination) and brain imaging are adjuncts that help in formulating the diagnosis. Referral to a hospital memory clinic activates a multidisciplinary team approach to dementia, including clinical consultation, dementia counselling, physiotherapy sessions on gait/fall prevention, occupational therapy sessions on cognitive stimulation and caregiver training.
17Neurological consequences of adult-onset hypothyroidism.PubMed
Izuki Amano, Ayane Ninomiya, Noriyuki Koibuchi
Endocr J. 2025 Nov 4;72(11):1175-1187. doi: 10.1507/endocrj.EJ25-0163. Epub 2025 Jun 4.
Adult-onset hypothyroidism has long been recognized as a reversible cause of cognitive impairment. However, recent studies have shown that it is associated with structural brain alterations besides functional alterations, particularly in the hippocampus and prefrontal cortex. Neurophysiological and molecular studies have demonstrated that hypothyroidism impairs synaptic plasticity, disrupts neurotransmitter signaling, and promotes neuroinflammation, leading to learning and memory impairments. The condition also affects adult neurogenesis, particularly in the hippocampal dentate gyrus. Moreover, hypothyroidism has been linked to psychiatric disorders, including depression and anxiety, through its influence on the plasticity of the amygdala. In addition, adult-onset hypothyroidism contributes to cerebellar ataxia and peripheral neuropathy, impacting motor coordination and sensory processing. Since we come to know that adult-onset hypothyroidism in part causes irreversible changes in brain structure, prompt treatment is crucial. Furthermore, in addition to thyroid field, recent studies suggest a potential of thyroid hormone treatment beyond the thyroid disorders, such as neurodegenerative and cognitive/psychiatric disorders. This review highlights the critical role of THs in maintaining neural function and explores their therapeutic potential in addressing neurological and psychiatric conditions.
18The Association of Thyroid Disease with Risk of Dementia and Cognitive Impairment: A Systematic Review.PubMed
Silvija Valdonė Alšauskė, Ida Liseckienė, Rasa Verkauskienė
Medicina (Kaunas). 2024 Nov 21;60(12):1917. doi: 10.3390/medicina60121917.
: Cognitive impairment is defined as a reduced ability to perform one or more cognitive functions, potentially leading to dementia if the condition worsens. With dementia being a rapidly growing public health issue affecting approximately 50 million people worldwide, understanding modifiable risk factors such as thyroid disease is crucial for prevention and early diagnosis. Thyroid hormones play a vital role in brain development and functioning, impacting processes such as neuron growth, myelination, and neurotransmitter synthesis. Recent decades have seen thyroid disorders emerging as potential independent risk factors for reversible cognitive impairment. : The review adheres to PRISMA guidelines, utilizing a structured PICO question to explore whether individuals with thyroid diseases have a higher risk of developing dementia and cognitive impairments compared to those without. The literature search was conducted in PubMed, Cochrane, and ScienceDirect databases, including studies published from 1 January 2019 to 31 December 2023. The literature review discusses nine selected articles. : The findings highlight a complex association between thyroid dysfunction and cognitive decline, with some studies indicating significant links, particularly with hypothyroidism, and others suggesting the relationship may depend on the specific type of thyroid dysfunction or cognitive domain affected. Six out of nine articles found a link between thyroid disease and cognitive impairment, while three articles refuted this link. : The review reveals a complex and ambiguous relationship between thyroid dysfunction and cognitive impairment. Further research is needed to elucidate the mechanisms underlying these associations and to determine whether thyroid dysfunction may be a modifiable risk factor for dementia.
19Treatable dementias.PubMed
M E Mahler, J L Cummings, D F Benson
West J Med. 1987 Jun;146(6):705-12.
Dementia is an acquired impairment of intellect produced by brain dysfunction. In the past, dementia was regarded as inevitably chronic, progressive and irreversible. More recently dementia has been viewed as a clinical syndrome that may be produced by both irreversible and reversible conditions. Recognition of the presence of a dementia syndrome should be followed by an evaluation for potentially treatable causes of the intellectual deterioration. Dementia treatment includes therapy for reversible or curable dementias and nonspecific interventions that may improve the condition of patients with progressive dementia syndromes.
20Prevalence and influencing factors of cognitive frailty among Chinese older adults: A systematic review and meta-analysis.PubMed
Xie Lin, Zhong Nian, Liu Yang, et al.
Int J Nurs Pract. 2024 Dec;30(6):e13306. doi: 10.1111/ijn.13306. Epub 2024 Oct 24.
AIMS: Cognitive frailty refers to the coexistence of physical frailty and cognitive impairment in older adults, without a concurrent diagnosis of Alzheimer's disease or other dementias. This review aims to evaluate the prevalence of CF subtypes and identify influencing factors among Chinese older adults. METHODS: The following databases were searched: PubMed/Medline, Embase, Cochrane Library, WOS, PsycINFO and CNKI et al (1 January 2001 to 20 October 2022). The risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-based Practice Center Methods Guide. Stata 17.0 software was used to pool the prevalence of cognitive frailty, and the pooled odds ratio and 95% CI of the influencing factors were calculated. RESULTS: The meta-analysis (56 studies and 80,320 participants) revealed the following prevalence rates: CF (18.9%), reversible CF (19.5%), potentially reversible CF (17.5%), CF in community-dwelling older adults (14.3%), CF in nursing homes (22.7%) and CF in older inpatients (25.2%). Influential factors identified included age, gender, education, nutrition, depression, exercise, sleep and comorbidity. CONCLUSIONS: The prevalence of CF among Chinese older adults is notably high, and it probably underestimates the prevalence of reversible cognitive frailty. It is crucial to encourage adherence to healthy behaviours, as it can effectively reduce and delay the onset of cognitive frailty.