Age-related hearing loss and tinnitus, dementia risk, and auditory amplification outcomes

Introduction Subjective chronic tinnitus is a common medical syndrome with a high frequency of cognitive impairment; however, the characteristics of cognitive impairment in chronic tinnitus are poorly understood. Investigating the scope of cognitive impairment across the severity spectrum of tinnitus patients may shed light on the issue. Methods A consecutive series of 207 subjective chronic tinnitus patients were classified into mild tinnitus group (n = 95) and severe tinnitus group (n = 112) by THI score (the cutoff THI scores were 37/38). These patients were assessed using the Cognitive Abilities Screening Instrument (CASI) and P300 event-related potential. Results Although pure tone averages were not different between mild or severe tinnitus patients, severe tinnitus patients scored lower on the CASI assessment as well as almost all subdomains of CASI, particularly in items such as "short-term memory," "concentration or mental manipulation," "orientation," "abstraction and judgment," "language abilities," and "visual construction." Furthermore, compared to mild tinnitus patients, severe tinnitus patients exhibited longer N2 and P3 latencies. Finally, a correlation analysis revealed that tinnitus severity was negatively correlated with CASI score and positively correlated with N2 and P3 latencies. Conclusions This study reveals that tinnitus patients on the severe end of the spectrum may be at risk for serious cognitive deficits, which may not be a secondary response to disease manifestations but a primary feature of the underlying disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/brb3.918

The characteristics of cognitive impairment in subjective chronic tinnitus

PURPOSE
Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources.


METHODS
The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using a spatial Stroop paradigm.


RESULTS
TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only.


CONCLUSIONS
Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers.

Altered top-down cognitive control and auditory processing in tinnitus: evidences from auditory and visual spatial stroop, Supplement information

Background Previous studies have demonstrated that cognitive impairment is linked with neurophysiological alterations in chronic tinnitus. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in tinnitus patients using a resting-state functional magnetic resonance imaging (rs-fMRI). Methods Thirty-five chronic unilateral tinnitus patients, and 50 healthy controls were recruited for rsfMRI scanning. Both groups were age, gender and education level well-matched. The posterior cingulate cortex (PCC) was chosen as the region of interest (ROI) for detecting the FC changes, and determining if these abnormalities were related to a specific cognitive performance and tinnitus characteristic. Results Relative to the healthy controls, tinnitus patients showed increased FC between the PCC and the right medial prefrontal cortex (mPFC). Moreover, the enhanced FC between the PCC and right mPFC was correlated with the poorer TMT-B scores (r=0.474, P=0.008). These correlations were adjusted by age, gender, education level, GM volume, and mean hearing thresholds. The enhanced FC was not correlated with other tinnitus characteristics or cognitive performances. Conclusions The enhanced FC pattern of the PCC that is correlated with cognitive impairment in chronic tinnitus patients, especially the executive dysfunction. Enhanced connectivity pattern within the DMN may play a crucial role in neurophysiological mechanism in tinnitus patients with cognitive dysfunction.

/pdf/alterations-of-the-default-mode-network-and-cognitive-lnied9xtjc.pdf

Alterations of the default mode network and cognitive impairment in patients with unilateral chronic tinnitus.

Tinnitus patients can present with various characteristics, such as those related to the tinnitus perception, symptom severity, and pattern of comorbidities. It is speculated that this phenotypic heterogeneity is associated with differences in the underlying pathophysiology and personal reaction to the condition. However, there is as yet no established protocol for tinnitus profiling or subtyping, hindering progress in treatment development. This review summarizes data on variables that have been used in studies investigating phenotypic differences in subgroups of tinnitus, including variables used to both define and compare subgroups. A PubMed search led to the identification of 64 eligible articles. In most studies, variables for subgrouping were chosen by the researchers (hypothesis-driven approach). Other approaches included application of unsupervised machine-learning techniques for the definition of subgroups (data-driven), and subgroup definition based on the response to a tinnitus treatment (treatment response). A framework of 94 variable concepts was created to summarize variables used across all studies. Frequency statistics for the use of each variable concept are presented, demonstrating those most and least commonly assessed. This review highlights the high dimensionality of tinnitus heterogeneity. The framework of variables can contribute to the design of future studies, helping to decide on tinnitus assessment and subgrouping.

https://www.mdpi.com/2076-3425/10/12/938/pdf

A Review and a Framework of Variables for Defining and Characterizing Tinnitus Subphenotypes.

BACKGROUND
The present study analyzed the relationship between circulating Trimethylamine N-oxide (TMAO) levels and stroke severity in diabetic patients with acute ischemic stroke. A further aim was to investigate whether higher TMAO levels were associated with platelet aggregation and glycemic variability.


METHODS
This was a cross-sectional analysis of 108 patients with type 2 diabetes mellitus (DM) undergoing acute ischemic stroke and 60 healthy controls. Fasting plasma TMAO was measured using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry.


RESULTS
Plasma TMAO levels of patients with acute ischemic stroke were significantly higher than those of healthy controls. Among stroke patients, 50 were defined as undergoing mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke. Platelet aggregation and mean amplitude of glycemic excursions (MAGE) were both correlated with plasma TMAO levels and these relationships remained significant in multiple linear regression analyses. Moreover, in streptozotocin-induced diabetic rats fed a diet enriched with choline to increase TMAO synthesis, platelet aggregation was significantly increased in the DM+choline and fluctuated DM (FDM)+Choline groups compared to the Control group. This increase was abolished in rats receiving oral ABS, which markedly reduced plasma TMAO levels. Importantly, compared with the DM+choline group, the FDM+Choline group displayed significantly elevated TMAO levels and higher platelet aggregation.


CONCLUSIONS
Our results demonstrated that higher plasma TMAO levels were associated with stroke severity and suggested a novel link between plasma TMAO levels and glycemic variability in diabetic patients with acute ischemic stroke.

Trimethylamine-N-oxide predicts stroke severity in diabetic patients with acute ischemic stroke and is related to glycemic variability.

Background Reliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD. Materials and methods A prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers. Results The gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients. Conclusion Brain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

/pdf/potential-of-brain-age-in-identifying-early-cognitive-1tf3a7an.pdf

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients

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Papers

The characteristics of cognitive impairment in subjective chronic tinnitus

Trimethylamine-N-oxide predicts stroke severity in diabetic patients with acute ischemic stroke and is related to glycemic variability.

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients