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T helper 17 (Th17) cells represent a distinct population of immune cells, important in the defense of the organism against extracellular infectious agents. Because of their cytokine profile and ability to recruit other immune cell types, they are highly pro-inflammatory and are involved in the induction of several autoimmune disorders. Recent studies show that Th17 cells and their signature cytokine IL-17 have also a role in a wide variety of neurological diseases. This review article will briefly summarize the evidence linking Th17 cells to brain diseases associated with cognitive impairment, including multiple sclerosis (MS), ischemic brain injury and Alzheimer’s disease (AD). We will also investigate the mechanisms by which these cells enter the brain and induce brain damage, including direct effects of IL-17 on brain cells and indirect effects mediated through disruption of the blood-brain barrier (BBB), neurovascular dysfunction and gut-brain axis. Finally, therapeutic prospects targeting Th17 cells and IL-17 will be discussed.

Vascular pathology is the second most common neuropathology of dementia after Alzheimer’s disease (AD), with small vessels disease (SVD) being considered the major cause of vascular cognitive impairment and dementia (VCID). This review aims to evaluate pathophysiological pathways underlying a diagnosis of VCID. Firstly, we will discuss the role of endothelial dysfunction, blood-brain barrier disruption and neuroinflammation in its pathogenesis. Then, we will analyse different biomarkers including the ones of inflammatory responses to central nervous system tissue injuries, of coagulation and thrombosis and of circulating microRNA. Evidences on peripheral biomarkers for VCID are still poor and large-scale, prospectively designed studies are needed to translate these findings into clinical practice, in order to set different combinations of biomarkers to use for differential diagnosis among types of dementia.

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Aims: To investigate, in a group of subjects with cognitive impairment, the relationship between anosognosia, in each dimension of insight, and neuropsychological domains. Methods: Two hundred and seventy-one subjects affected by cognitive impairment were consecutively enrolled. Anosognosia was evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level of cognitive impairment was evaluated by means of the Mini-Mental State Examination, while 8 cognitive domains were examined by means of neuropsychological tests. Results: The number of subjects with anosognosia evaluated by means of the CIRS total score as well as those with anosognosia divided according to the reason for visit was higher in moderately cognitively impaired subjects than in mildly cognitively impaired subjects (p < 0.001). A relationship between anosognosia and neuropsychological scores was only found in mild cognitive impairment, with subjects with anosognosia displaying significantly lower Raven’s Colored Progressive Matrices Test and Rey Auditory Verbal Learning Test-delayed recall scores than subjects without anosognosia. Conclusions: Our study suggests that the relationship between the severity of cognitive deficits and anosognosia in subjects with cognitive impairment is partial and depends on the specific domain of unawareness. Furthermore, in the early phase of cognitive impairment, the presence of specific cognitive deficits suggests that the nature of anosognosia is domain-specific.

Aims: To investigate, in a group of subjects at an early stage of cognitive impairment, the relationship between anosognosia and both cognitive and behavioral symptoms by exploring the various domains of insight. Methods: One hundred and eight subjects affected by cognitive impairment were consecutively enrolled. The level of awareness was evaluated by means of the Clinical Insight Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index, MI) and executive (executive index, EI) functions were explored using a battery of neuropsychological tests and qualified by means of a single composite cognitive index score for each function. Results: A significant positive correlation between the total NPI score and global anosognosia score was found. Furthermore, both the MI and EI scores were lower in subjects with anosognosia than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When the single domains of the CIRS were considered, anosognosia of reason of visit correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040); anosognosia of functional deficit correlated with the MI score (r = -0.257; p = 0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289; p = 0.003); anosognosia of disease progression correlated with the MI score (r = -0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r = 0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027). Conclusions: Our study suggests that, in the early stage of cognitive impairment, anosognosia is associated with both cognitive deficits and behavioral disorders according to the specific functional anatomy of the symptoms.

In normal old (Nold) and Alzheimer’s disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu–) educational attainment subgroups, were available in an Italian–Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu– subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu– subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray–white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

Background: The relation of retinal thickness to neuropsychological indexes of cognitive impairment in patients with Alzheimer disease (AD) remains an area of investigation. The scope of this investigation was to compare volume and thickness changes of neuronal retinal layers in subjects with AD with those of age-matched healthy controls and to estimate the relation between cognitive functioning evaluated by neuropsychological assessment and thickness changes of the retina. Methods: This was a prospective single-site study where we evaluated 25 subjects with probable AD matched for age, sex, and education to 17 healthy control subjects (HC). All participants underwent a full medical evaluation, neuropsychological assessment, and optical coherence tomography (OCT) to evaluate the peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell complex (GCC) thickness, and macular volume. Results: The pRNFL thickness of AD patients showed a significant overall reduction compared with healthy controls (P = <0.0001). Furthermore, pRNFL was reduced in each retinal quadrant, particularly the inferior, nasal, and superior quadrants. GCC thickness and macular volume were reduced in AD patients in comparison with HC (P = 0.004; P = 0.001). Of particular interest was the correlation between OCT findings and neuropsychological assessment; we did not find a significant association of retinal thinning with worse MMSE score, but reduction of macular volume was associated with worse constructional praxis performance. Impairment of semantic-lexical and processing speed was associated with attenuation of macular GCC thickness. Conclusions: OCT can show early thickness changes in AD patients with subtle memory disturbances. These results suggest that correlations between retinal thinning and cognitive performance warrant further investigation.