Visual Event-Related Potentials under External Emotional Stimuli as Early Signs for Mild Cognitive Impairment.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder featured by progressive cognitive decline, which manifests in severe impairment of memory, attention, emotional processing and daily activities, leading to significant disability and social burden. Investigation on Mild Cognitive Impairment (MCI), the prodromal and transitional stage between normal aging and AD, serves as a key in diagnosing and slowing down the progression of AD. Numerous effects have been made up to date, however, the attentional mechanisms under different external emotion stimuli in MCI and AD are still unexplored in deep. OBJECTIVE: To further explore the attentional mechanisms under different external emotion stimuli in both MCI and AD patients. DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: In 51 healthy volunteers (Controls, 24 males and 27 females), 52 MCI (19 males and 33 females), and 47 AD (15 males and 32 females) patients, we administered the visual oddball event-related potentials (ERPs) under three types of external emotional stimuli: Neutral, Happiness and Sadness, in which the components N1, P2, N2 and P3 as well as the abnormal cortical activations corresponding to the significant ERP differences in the three groups were observed. RESULTS: Under all three external emotions, in AD patients, N2 and P3 latencies were significantly prolonged compared to both Controls and MCI. In addition, under Happiness, in MCI, P3 latencies were significantly delayed compared to Controls. Meanwhile, under both Happiness and Sadness, in AD patients, P3 amplitudes were significantly decreased compared to Controls and MCI, respectively. During N2 time window, under Neutral emotion, significant hypoactivation in the right superior temporal gyrus was found in AD patients compared to Controls, and under Happiness, the activation of the right inferior frontal gyrus was significantly attenuated in MCI compared to Controls. Under Sadness, in AD patients, the activation of the right superior frontal gyrus was significantly decreased compared to MCI. During P3 time window, under both Happiness and Sadness, when AD patients compared to MCI, the significantly attenuated activations were located in the right fusiform gyrus and the right middle occipital gyrus, respectively. CONCLUSION: Our results demonstrated visual attentional deficits under external emotional stimuli in both MCI and AD patients, highlighting the function of Happiness for early detecting MCI, in which the P3 latency and the hypoactivation of right inferior frontal gyrus during N2 time window can be early signs. The current study sheds further light of attentional mechanisms in MCI and AD patients, and indicates the value of emotional processing in the early detection of cognitive dysfunction.

Psychological outcomes of dementia risk estimation in MCI patients: Results from the PreDADQoL project.

INTRODUCTION: Understanding the impact of biomarker-based dementia risk estimation in people with mild cognitive impairment (MCI) and their care partners is critical for patient care. METHODS: MCI patients and study partners were counseled on Alzheimer's disease (AD) biomarker and dementia risk was disclosed. Data on mood, quality of life (QoL), and satisfaction with life (SwL) were obtained 1 week and 3 months after disclosure. RESULTS: Seventy-six dyads were enrolled, and two-thirds of the patients opted for biomarker testing. None of the participants experienced clinically relevant depression or anxiety after disclosure. All dyads reported moderate to high QoL and SwL throughout the study. Patients reported more subthreshold depressive symptoms 1 week and lower QoL and SwL 3 months after disclosure. In patients, depression (odds ratio [OR]: 0.76) and anxiety (OR: 0.81) were significant predictors for the decision against biomarker testing. DISCUSSION: No major psychological harm is to be expected in MCI patients and care partners after dementia risk disclosure. TRIAL REGISTRATION: This study is registered in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS): http://www.drks.de/DRKS00011155, DRKS registration number: DRKS00011155, date of registration: 18.08.2017. HIGHLIGHTS: Patients with mild cognitive impairment (MCI) and study partners were counseled on Alzheimer's disease (AD) biomarker-based dementia risk estimation. About two-thirds of patients opted for biomarker testing and received their dementia risk based on their AD biomarker status. Patients who decided in favor or against CSF biomarker testing differed in psychological features. We did not observe major psychological harm after the dementia risk disclosure. Coping strategies were associated with better subsequent mood and well-being in all participants.

Prevalence Estimation of Dementia/Alzheimer's Disease Using Health and Retirement Study Database in the United States.

BACKGROUND: Updated prevalence estimates along the continuum of Alzheimer's disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape. OBJECTIVES: This study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS). DESIGN: Retrospective study. SETTING: Data from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years. PARTICIPANTS: Dementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020). MEASUREMENTS: AD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample's representativeness of the target population and unbiased estimates for population parameters. RESULTS: Across the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23-27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD. CONCLUSION: The prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.

Progress in the Treatment of Alzheimer's Disease Is Needed - Position Statement of European Alzheimer's Disease Consortium (EADC) Investigators.

ß-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer's disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer's Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current ß-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases.

Continuous Associations between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer's Disease.

BACKGROUND: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer's disease (AD) dementia risk are critical for timely intervention. OBJECTIVES/DESIGN: This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD) - a remote, self-administered, multi-device compatible, web-based cognitive assessment - and AD-related imaging biomarkers. PARTICIPANTS/SETTING: 684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center participated (age=70.4±11.2, 49.7% female). Participants were predominantly cognitively unimpaired (CU; 94.0%). MEASUREMENTS: Participants completed (1) brain amyloid and tau PET scans and MRI scans for hippocampal volume (HV) and white matter hyperintensities (WMH); (2) MTD remotely, consisting of the Stricker Learning Span and Symbols Test which combine into an MTD composite; and (3) in-person neuropsychological assessment including measures to obtain Mayo Preclinical Alzheimer's disease Cognitive Composite (Mayo-PACC) and Global-z. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers and scores from remote and in-person cognitive measures. RESULTS: Lower performances on MTD were associated with greater amyloid, entorhinal tau, and global tau PET burden, lower HV, and higher WMH. Mayo-PACC and Global-z were associated with all imaging biomarkers except global tau PET burden. MCI/Dementia participants showed lower performance on all MTD measures compared to CU with large effect sizes (Hedge's g's=1.65-2.02), with similar findings for CU versus MCI only (Hedge's g's=1.46-1.83). CONCLUSION: MTD is associated with continuous measures of AD-related imaging biomarkers, demonstrating ability to detect subtle cognitive change using a brief, remote assessment in predominantly CU individuals and criterion validity for MTD.

Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review).

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of ß-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.

Validity of the Tablet-Based Digital Cognitive Test (SCST) in Identifying Different Degrees of Cognitive Impairment.

BACKGROUND: As society ages, the incidence of Alzheimer's disease and other dementias has surged, highlighting the importance of early dementia diagnosis. The Seoul Cognitive Status Test (SCST), a digital neuropsychological test, is designed for the early detection of cognitive impairment and has been standardized to establish reliability and validity. This study aims to verify whether the SCST effectively discriminates between groups based on three cognitive statuses (subjective cognitive decline [SCD], mild cognitive impairment [MCI], Dementia) in a large sample. We also seek to determine whether the SCST discriminates between individuals with three different cognitive statuses as defined by the Cognitive Dementia Rating (CDR). METHODS: We enrolled 254 participants from a dementia clinic who underwent a comprehensive neuropsychological battery (Seoul Neuropsychological Screening Battery-II) during the dementia evaluation by experienced neurologists (55 with SCD, 126 with MCI, 73 with dementia). In addition, the degree of cognitive decline in participants was classified by CDR level (186 with CDR 0.5, 52 with CDR 1, 15 with CDR 2). One-way analysis of variance was used to compare SCST scores according to each of the three cognitive status groups and CDR levels. RESULTS: The SCST total score, cognitive domain scores (attention, language, visuospatial function, memory, executive function), and most of the subtest scores decreased significantly in the order of SCD, MCI and dementia. Likewise, the differences in SCST scores between CDR levels were significant, particularly in distinguishing between CDR 0.5 and CDR 1. CONCLUSION: This study reaffirmed that the SCST can significantly discriminate between groups of individuals with SCD, MCI, and dementia based on a large sample. Furthermore, differences in SCT scores were found across the levels of CDR, confirming the clinical utility of the SCST. These findings suggest that the SCST is an efficient and useful neuropsychological test for the sensitive detection of early cognitive impairment.

Mild Cognitive Impairment, Religiosity, Spirituality and all-Cause Mortality Among Chinese Older Adults in Ethnic Minority Communities.

The relationship between mild cognitive impairment (MCI), religiosity and/or spirituality (R/S), and all-cause mortality among older adults has yet to be clarified. The current study aims to examine this relationship using a longitudinal cohort from ethnic minority communities in mainland China. The Cox proportional hazards regression modeling revealed that MCI predicted an increased risk of all-cause mortality, and high R/S buffered this association. Those findings suggest that a religious-spiritual integrated community intervention program may reduce the mortality risk in older adults with MCI in ethnically disadvantaged populations.

Toward an intelligent computing system for the early diagnosis of Alzheimer's disease based on the modular hybrid growing neural gas.

Objective: The proportion of older people will soon include nearly a quarter of the world population. This leads to an increased prevalence of non-communicable diseases such as Alzheimer's disease (AD), a progressive neurodegenerative disorder and the most common dementia. mild cognitive impairment (MCI) can be considered its prodromal stage. The early diagnosis of AD is a huge issue. We face it by solving these classification tasks: MCI-AD and cognitively normal (CN)-MCI-AD. Methods: An intelligent computing system has been developed and implemented to face both challenges. A non-neural preprocessing module was followed by a processing one based on a hybrid and ontogenetic neural architecture, the modular hybrid growing neural gas (MyGNG). The MyGNG is hierarchically organized, with a growing neural gas (GNG) for clustering followed by a perceptron for labeling. For each task, 495 and 819 patients from the Alzheimer's disease neuroimaging initiative (ADNI) database were used, respectively, each with 211 characteristics. Results: Encouraging results have been obtained in the MCI-AD classification task, reaching values of area under the curve (AUC) of 0.96 and sensitivity of 0.91, whereas 0.86 and 0.9 in CN-MCI-AD. Furthermore, a comparative study with popular machine learning (ML) models was also performed for each of these tasks. Conclusions: The MyGNG proved to be a better computational solution than the other ML methods analyzed. Also, it had a similar performance to other deep learning schemes with neuroimaging. Our findings suggest that our proposal may be an interesting computing solution for the early diagnosis of AD.

Microglial responses partially mediate the effect of Aß on cognition in Alzheimer's disease.

INTRODUCTION: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aß) deposition. This study aimed to investigate the effects of Aß and microglial responses on global cognitive impairment. METHODS: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11C-PK11195 and 11C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aß load and global cognition was assessed. RESULTS: Aß load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aß load and global cognitive ratings was partially mediated by the microglial response. DISCUSSION: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aß on cognition. HIGHLIGHTS: This was a longitudinal study of amyloid beta (Aß), microglial responses, and global cognitive performance. Aß and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aß on cognition in later stages.

The Association Between Plasma Amyloid-ß 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-ß (Aß) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective: Plasma Aß biomarkers including the Aß42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). Methods: This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aß42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aß positivity (Aß+), while 50 aMCI participants scored above this cut-off indicating Aß negative status (Aß-). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aß-). Results: The aMCI plasma Aß+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aß-. The CU Aß- group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aß+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aß-group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aß- participants evidenced deficits, compared to 37.8% of aMCI Aß-, and 74.0% of aMCI Aß+. Conclusions: SIEs reflecting frPSI were associated with aMCI Aß+ status based on the Aß42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Disconnection of alpha oscillations within default mode network associated with memory dysfunction in amnestic MCI.

OBJECTIVE: Episodic memory dysfunction and alterations of functional connectivity (FC) in default mode network (DMN) were found in patients with amnestic mild cognitive impairment (aMCI). However, previous studies were limited in probing certain oscillations within the DMN. This study employed measures of resting-state FC across various oscillations within the DMN to comprehensively examine the FC and its association with episodic memory performance in aMCI. METHODS: Twenty-six healthy controls (HC) and 30 patients with aMCI were recruited to perform resting-state magnetoencephalographic recordings. We compared the spectral powers and peak frequency values in each frequency band and FC within the DMN between these two groups. The associations of FC values with memory performance were also examined. RESULTS: No significant between-group differences in spectral powers and peak frequency values were observed in the regional nodes. Patients with aMCI exhibited diminished alpha-band FC as compared to HC. Furthermore, lower alpha-band FC between the medial temporal cortex - and the posterior cingulate cortex/precuneus was correlated with poorer memory performance. CONCLUSIONS: Aberrant DMN connectivity, particularly in the alpha frequency range, might be a neural correlate of episodic memory impairment. SIGNIFICANCE: Our results inform the potential development of brain stimulation in managing memory impairments in aMCI.

Mendelian randomization in Alzheimer's disease and mild cognitive impairment: Hippocampal volume associations.

This study investigates the association between cognitive dysfunction and hippocampal volumes in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) using Mendelian randomization. A meta-analysis of 503 healthy controls, 562 MCI patients, and 389 CE patients revealed significant reductions in hippocampal and subregion volumes in MCI and AD compared to controls. While various subregions showed volume reductions, no causal relationship between hippocampal volume and AD was established through Mendelian randomization analysis. In conclusion, significant volume reductions were observed in MCI and AD patients, highlighting the complexity of the relationship between hippocampal volume and cognitive impairment.

Disruptive and complementary effects of depression symptoms on spontaneous brain activity in the subcortical vascular mild cognitive impairment.

Background: Although depression symptoms are commonly reported in patients with subcortical vascular mild cognitive impairment (svMCI), their impact on brain functions remains largely unknown, with diagnoses mainly dependent on behavioral assessments. Methods: In this study, we analyzed resting-state fMRI data from a cohort of 34 svMCI patients, comprising 18 patients with depression symptoms (svMCI+D) and 16 patients without (svMCI-D), along with 34 normal controls (NC). The study used the fraction of the amplitude of low-frequency fluctuations (fALFF), resting-state functional connectivity, correlation analyses, and support vector machine (SVM) techniques. Results: The fALFF of the right cerebellum (CERE.R) differed among the svMCI+D, svMCI-D, and NC groups. Specifically, the regional mean fALFF of CERE. R was lower in svMCI-D patients compared to NC but higher in svMCI+D patients compared to svMCI-D patients. Moreover, the adjusted fALFF of CERE. R showed a significant correlation with Montreal Cognitive Assessment (MOCA) scores in svMCI-D patients. The fALFF of the right orbital part of the superior frontal gyrus was significantly correlated with Hamilton Depression Scale scores in svMCI+D patients, whereas the fALFF of the right postcingulate cortex (PCC.R) showed a significant correlation with MOCA scores in svMCI-D patients. Furthermore, RSFC between PCC. R and right precuneus, as well as between CERE. R and the right lingual gyrus (LING.R), was significantly reduced in svMCI-D patients compared to NC. In regional analyses, the adjusted RSFC between PCC. R and PreCUN. R, as well as between CERE. R and LING. R, was decreased in svMCI-D patients compared to NC but increased in svMCI+D patients compared to svMCI-D. Further SVM analyses achieved good performances, with an area under the curve (AUC) of 0.82 for classifying svMCI+D, svMCI-D, and NC; 0.96 for classifying svMCI+D and svMCI-D; 0.82 for classifying svMCI+D and NC; and 0.92 for classifying svMCI-D and NC. Conclusion: The study revealed disruptive effects of cognitive impairment, along with both disruptive and complementary effects of depression symptoms on spontaneous brain activity in svMCI. Moreover, these findings suggest that the identified features might serve as potential biomarkers for distinguishing between svMCI+D, svMCI-D, and NC, thereby guiding clinical treatments such as transcranial magnetic stimulation for svMCI.

Mind Language Disturbances and PET-Signs of Depression vs Alzheimer's Disease: Are There Any Common Patterns Identified?

BACKGROUND: There is a broad appreciation that a diagnosis of depression (D) in the elderly is a strong risk factor for incident dementia, particularly Alzheimer's disease (AD). Indeed, the two disorders might constitute a dyad, although their causal relationship is uncertain, given the likely bidirectional and compounding effects of social withdrawal and loss of previous activities, and the manifestation of language disturbances, cognitive dysfunction, and social disruption that are typical of both conditions. We argue that language declines in D and AD share common patterns and biological underpinnings, and that D/AD patients might benefit from intensive language remediation training aiming to improve the functioning of neural networks that are linked to similar cognitive impairments. METHODS: A literature search in PubMed database included topics of language disturbances, cognitive impairments, and molecular brain imaging by positron emission tomography (PET) to identify common patterns in D and AD regarding language decline and its neurobiological underpinnings. RESULTS: Language disturbances show a particular commonality in the two disorders, manifesting in simplified language and particular speech markers (e.g., lexical and semantic repetitions, arguably due to ruminations in D and memory deficits in AD). PET can reveal abnormal protein deposits that are practically diagnostic of AD, but cerebrometabolic deficits to PET with the glucose tracer FDG show a certain commonality in D and AD. Typical findings of hypometabolism in the frontal lobes doubtless underlie the executive function deficits, where frontal hypometabolism in prodromal D increases with AD progression. This may reflect overlapping changes in noradrenaline and other neurotransmitter (e.g. serotonin) changes. Cerebrometabolic deficits associated with language dysfunction may inform targeted language remediation treatments in the D/AD progression. CONCLUSIONS: Language remediation techniques targeting specific language disturbances might present an important complimentary treatment strategy along with an adjusted pharmacotherapy approach and standard psychosocial rehabilitation interventions. We see a need for investigations of language remediation informed by the overlapping pathologies and language disturbances in D and AD.

Cholinesterase inhibitor use in amyloid PET-negative mild cognitive impairment and cognitive changes.

BACKGROUND: Cholinesterase inhibitors (ChEIs) are prescribed for Alzheimer's disease (AD) and sometimes for mild cognitive impairment (MCI) without knowing underlying pathologies and its effect on cognition. We investigated the frequency of ChEI prescriptions in amyloid-negative MCI and their association with cognitive changes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. METHODS: We included participants with amyloid positron emission tomography (PET)-negative MCI from the ADNI. We analyzed the associations of ChEI use with cognitive changes, brain volume, and cerebrospinal fluid (CSF) total tau (t-tau), hyperphosphorylated tau181 (p-tau181), and p-tau181/t-tau ratio. RESULTS: ChEIs were prescribed in 27.4% of amyloid PET-negative MCI and were associated with faster cognitive decline, reduced baseline hippocampal volume and entorhinal cortical thickness, and a longitudinal decrease in the frontal lobe cortical thickness. CONCLUSIONS: The association between ChEI use and accelerated cognitive decline may stem from underlying pathologies involving reduced hippocampal volume, entorhinal cortical thickness and faster frontal lobe atrophy. We suggest that ChEI use in amyloid PET-negative MCI patients might need further consideration, and studies investigating the causality between ChEI use and cognitive decline are warranted in the future.

Task-evoked pupillary responses as potential biomarkers of mild cognitive impairment.

INTRODUCTION: Eye movement alterations are effective biomarkers for Alzheimer's disease (AD). This study examines task-evoked pupillary responses (TEPRs) as potential biomarkers of the mild cognitive impairment (MCI), the symptomatic stage preceding AD. METHODS: The prospective cohort study included 213 MCI patients and 514 cognitively normal controls (CNs). Participants performed a prosaccade (PS) or antisaccade (AS) task while their eye movements were tracked using a Tobii Pro Spectrum system. RESULTS: The CNs showed unique TEPRs linked to better performance, characterized by larger baselines, greater PS target-onset variability, and smaller AS target-onset variability. Conversely, for MCI patients, better performance was linked to larger AS target-onset sizes. Furthermore, MCI patients displayed reduced dilation during the cue and target-onset periods compared to CNs. DISCUSSION: MCI patients showed altered pupillary response patterns associated with cognitive task performance, highlighting the potential of oculomotor changes as a biomarker for early cognitive decline. Highlights: MCI patients displayed markedly smaller pupil dilation than CNs in response to cue and target stimuli.For MCI patients, larger pupil size upon target appearance during antisaccades correlated with better performance.Faster and more consistent prosaccades were linked to better performance in both groups.For MCI patients, the association between longer AS latencies and better performance was more pronounced than in CNs.Combined analysis of TEPRs and saccade performances in a sizeable cohort strengthens the generalizability of our findings to the broader MCI population.

A systematic review of the effect and mechanism of Daoyin therapy on improving mild cognitive impairment in older adults.

BACKGROUND: Age-related cognitive decline is a pervasive problem in the aging population. Daoyin therapy is a mind-body movement characteristic of traditional Chinese medicine (TCM). Increasing evidence has reported its usefulness in improving cognitive function among different populations. However, there is no systematic review to assess the effect and mechanism of Daoyin therapy on mild cognitive dysfunction (MCI) in older adults. OBJECTIVE: To systematically review the evidence on the effect and mechanism of Daoyin therapy on MCI in older adults. RESULTS: Taichi, Baduanjin, and Yijinjing can improve cognitive function. Qigong and Wuqinxi can enhance the physical and cognitive functions related to balance, muscle strength, physical endurance, postural control, and flexibility. Taichi, Baduanjin, and Wuqinxi can improve the cognitive function of older adults and alleviate the symptoms associated with MCI through multiple mechanisms. The underlying mechanisms include activating the expression of signals and changing their connections in different brain regions, increasing brain capacity, and regulating brain-derived neurotropic and inflammatory factors. CONCLUSION: In summary, the existing evidence from RCTs suggests that traditional Daoyin therapy, such as Taichi, Baduanjin, and Wuqinxi, is a promising strategy that can improve cognitive function and delay the onset of dementia in older adults with MCI by altering structural and neural activities and modulating other factors.

Socio-economic inequalities in health-related quality of life and the contribution of cognitive impairment in Australia: A decomposition analysis.

BACKGROUND: The distributional effects of cognitive impairment on inequalities in health-related quality of life (HRQoL) are not well studied. This relationship has not been studied in any Australian health inequality literature. Therefore, this study aims to examine how cognitive impairment affects the distribution of HRQoL across various socio-economic classes amongst older Australians. METHODS: Data for this study was collected from the Household, Income and Labour Dynamics in Australia (HILDA) survey. The final analysis consisted of 5,247 and 5,614 unique individuals from wave 2012 and wave 2016, respectively. An ordinary least squares (OLS) regression model was used to investigate the relationship between cognitive impairment and HRQoL. Additionally, the Wagstaff-Doorslaer-Watanabe standard concentration index was used to examine socioeconomic inequality in HRQoL. RESULTS: The findings revealed pro-rich inequalities in HRQoL, as indicated by the concentration indices of 0.029 and 0.025 for wave 12 and wave 16, respectively. Additionally, the results showed that mild cognitive impairment accounted for 7.60% and 9.03%, respectively, of pro-rich socioeconomic inequality in HRQoL in 2012 and 2016. CONCLUSION: People from lower socioeconomic status (SES) groups tend to have lower HRQoL compared to those from higher SES. This leads to a greater disparity in HRQoL based on SES. Cognitive impairment positively contributed to this inequality in HRQoL. Therefore, it is critical to incorporate cognitive impairment into the design of interventions to reduce socioeconomic inequality in HRQoL.

Decision-making under uncertainty in healthy and cognitively impaired aging: A systematic review and meta-analysis.

Decision-making (DM) is a complex cognitive behavior that involves gathering information and assessing options to identify choices under risky and uncertain conditions. Mild Cognitive Impairment (MCI) is a construct that includes a constellation of symptoms ranging from behavioral to cognitive impairments. This cluster of symptoms is frequently associated with poor decision-making. This study aimed to examine decision-making in pathological aging, specifically MCI. Therefore, we conducted a systematic review and meta-analysis to evaluate these relationships. According to the PRISMA 2020 Statement, nine studies were selected for the systematic review and eight for the meta-analysis. The results highlighted that MCI is associated with impaired decision-making in risky and ambiguous situations. The systematic review reported that MCI was associated with impaired decision-making in ambiguous and in risky conditions. In contrast, the meta-analysis showed significant differences in overall decision-making and particularly in ambiguous conditions. This difficulty may be due to different impairments that affect MCI. The difficulty in advantageous decision-making could be due to different brain alterations in MCI, which could lead to problems in tasks requiring feedback-based responses. These findings advance our understanding of decision-making in aging and suggest how decision-making alterations in MCI would affect the totality of executive functions and daily activities.