Subjective Cognitive Impairment Research Articles

Cerebrospinal fluid HSP90AA1, HSPA4, and STUB1/CHIP levels in Alzheimer's disease, mild cognitive impairment, and frontotemporal dementia.

BackgroundThe data that we gathered from a protein-protein interaction (PPI) prediction tool, FpClass, and a limited number of studies indicated that the chaperones HSP90AA1, HSPA4, STUB1/CHIP might interact with amyloid-β (Aβ) and/or tau and could subsequently be co-released into the cerebrospinal fluid (CSF). Therefore, we investigated CSF levels of HSP90AA1, HSPA4, and STUB1/CHIP in Alzheimer's disease (AD), Non-AD mild cognitive impairment (Non-AD MCI), and frontotemporal dementia (FTD) cases.MethodsThe CSF levels of HSP90AA1, HSPA4, STUB/CHIP, and core AD biomarkers were determined by ELISA in AD (n = 90), Non-AD MCI (n = 27), FTD (n = 15), and subjective cognitive impairment (SCI) (n = 20) subjects.ResultsHSP90AA1 levels were significantly higher in AD cases compared to the SCI subjects. The CSF levels of STUB1/CHIP were significantly lower in AD, Non-AD MCI and FTD cases compared to the SCI subjects. STUB1/CHIP levels of FTD cases were significantly lower than all other groups. HSPA4 levels was correlated with core AD biomarkers (Aβ 1-42, p-Tau, t-Tau) regardless of disease. Non-APOE ε4 carrier FTD cases also had significantly lower STUB1/CHIP levels than other groups.ConclusionsThe STUB1/CHIP holds promise as a potential biomarker for distinguishing between SCI subjects, AD, and FTD. Furthermore, APOE might serve as an additional discriminatory factor that might be integrated with this chaperone for enhanced discrimination.

Extracted step parameters during the timed up and go test discriminate between groups with different levels of cognitive ability-a cross-sectional study.

Identifying cognitive impairment at an early stage is important to enable preventive treatment and lifestyle changes. As gait deviations precede cognitive impairment, the aim of this study was to investigate if step parameters during different Timed Up and Go (TUG) conditions could discriminate between people with different cognitive ability. Participants (N = 304) were divided into the following groups: (1) controls, n = 50, mean age:73, 44% women; (2) Subjective cognitive Impairment (SCI), n = 71, mean age:67, 45% women; (3) Mild Cognitive Impairment (MCI), n = 126, mean age: 73, 42% women; and (4) dementia disorders, n = 57, mean age: 78, 51% women. Participants conducted TUG and two motor-cognitive TUG-conditions: TUG while naming animals (TUGdt-NA) and reciting months in reverse order (TUGdt-MB). Tests were video recorded for data extraction of valid spatiotemporal parameters: step length, step width, step duration, single step duration and double step duration. Step length was investigated with the step length/body height ratio (step length divided by body height). Logistic regression models (adjusted for age, sex and education) investigated associations between step parameters and dichotomous variables of groups adjacent in cognitive ability: dementia disorders vs. MCI, MCI vs. SCI, and SCI vs. controls. Results were presented as standardized odds ratios (sORs), with 95% confidence intervals (CI95) and p-values (significance level: p < 0.05). The areas under the Receiver Operating Characteristic curves were presented for the step parameters/conditions with the highest sORs and, where relevant, optimal cutoff values were calculated. Step length showed greatest overall ability to significantly discriminate between adjacent groups (sOR ≤ . 67, CI95: .45-.99, p = ≤ . 047) during all group comparisons/conditions except three. The highest sOR for step-length was obtained when discriminating between SCI vs controls during TUGdt-MB (sOR = .51, CI95:.29- .87, p = .014), whereby the area under the curve was calculated (c-statistics = .700). The optimal cut-off indicated a step length of less than 32.9% (CI95 = 22.1-43.0) of body height to identify SCI compared with controls. The results indicate that step length may be important to assess during TUG, for discrimination between groups with different cognitive ability; and that the presented cut-off has potential to aid early detection of cognitive impairment. NCT05893524 (retrospectively registered 08/06/23).

Cerebral Hemodynamic Impairment and Cognitive Dysfunction in APOE4 Carriers With Asymptomatic Carotid Artery Stenosis/Occlusion.

Our previous preclinical study demonstrated that APOE4-targeted replacement mice exhibit more severe cerebral hypoperfusion and cognitive impairment than APOE3-targeted replacement mice with carotid artery stenosis due to neurovascular dysfunction. Therefore, we clinically investigate whether APOE4 contributes to cerebral hemodynamic and cognitive impairment in subjects with asymptomatic carotid artery stenosis or occlusion. A cross-sectional observational study was conducted between January 2017 and March 2022. In a primary analysis, 91 subjects (114 affected cerebral hemispheres) with asymptomatic carotid artery stenosis or occlusion who underwent neuropsychological examinations and 15O-gas positron emission tomography were included to examine associations of APOE4 with cognitive impairment and cerebral hemodynamic impairment. A sensitivity analysis was performed with 161 subjects (201 affected cerebral hemispheres) who underwent 15O-gas positron emission tomography scan. In the primary analysis, 20 (22.0%) subjects were APOE4 carriers. APOE4 was an independent risk factor of lower cerebral blood flow in the anterior circulation territory (β=-0.058 [95% CI, -0.098 to -0.018], P=0.005) and short-term memory impairment in Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (β=1.16 [95% CI, 0.009-2.30], P=0.048) in a multivariable linear regression analysis. In the sensitivity analysis, 31 (19.3%) subjects carried APOE4, which was an independent risk factor of lower cerebral blood flow (β=-0.048 [95% CI, -0.079 to -0.012], P=0.003) in the anterior circulation territory. APOE4 may confer an increased risk of decreased cerebral blood flow accompanied by memory impairment in asymptomatic carotid artery stenosis or occlusion consistent with our experimental study. APOE genotyping in such subjects may be useful for early detection of disease severity.

Rest activity rhythm fragmentation and synchronisation are linked with reduced cortical thickness in older adults 'at risk' for dementia.

While alterations in rest-activity rhythms are common in older adults 'at risk' for dementia, it is unclear how rest-activity rhythms relate to underlying brain integrity. Older adults aged > 50 years (n=143, mean age=67) with subjective and/or objective cognitive impairment underwent MRI scanning and 14-days of actigraphy. The following non-parametric measures were computed: intra-daily variability (IV), inter-daily stability (IS), relative amplitude (RA), and average activity during the least active 5-hour period (L5). A vertex-wise analysis correcting for age, sex and clinical variables examined the association between nonparametric actigraphy measures and cortical thickness. When controlling for age, sex, and body mass index (BMI), lower IV was associated with greater cortical thickness in the right cuneus (CWP< 0.001), left middle frontal gyrus (CWP< 0.001) and lateral orbital frontal cortex (CWP= 0.004). When controlling for age, sex, medical burden (CIRS-G), BMI and antidepressant use, lower IS was associated with lower cortical thickness in the left (CWP= 0.002) and right superior frontal gyrus (CWP< 0.001), left superior temporal gyrus (CWP= 0.043) and left post-central gyrus (CWP= 0.033). There were no significant associations between RA or L5 and cortical thickness. In older adults 'at risk' for dementia, variability and stability of rest-activity rhythms were associated with reduced cortical thickness in frontal, temporal, parietal and occipital regions. Studies are now required to determine the prognostic utility of such markers longitudinally.

Blood Biomarkers Reflect Dementia Symptoms and Are Influenced by Cerebrovascular Lesions.

Dementia blood biomarkers are becoming increasingly important. Various factors, such as ischemic lesions and inflammation, can influence the pathomechanism of dementia. We aimed to evaluate the effects of past stroke lesions on blood biomarkers (BMs). Following approval from the institutional ethics committee, patients who were admitted to the memory clinic and were consented to written documents were enrolled (n = 111, average [standard deviation] age: 74.5 [9.1] years-old). Brain magnetic resonance imaging, cognitive function, and neuropsychological symptoms were analyzed. The amyloid-β 42 (Aβ42)/Aβ40 ratio, phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and Aβ42/p-tau181 ratio were assessed as plasma BMs. The patients were diagnosed with Alzheimer's disease (n = 45), mild cognitive impairment (n = 56), depression (n = 8), and subjective cognitive impairment (n = 4). Bivariate analysis exhibited that all measured BM indicators were significantly associated with cognitive decline in patients without past stroke lesions. Whereas the patients with stroke lesions presented a significant association only between GFAP and cognitive decline (p = 0.0011). Multiple regression analysis showed that NfL significantly correlated with cognitive decline only in patients without stroke lesions (r = 0.4988, p = 0.0003) and with delusion only in those with stroke lesions (r = 0.5492, p = 0.0121). Past stroke lesions should be addressed in the assessment of the correlation between blood biomarkers and cognitive decline in dementia patients.

Comparing machine learning classifier models in discriminating cognitively unimpaired older adults from three clinical cohorts in the Alzheimer's disease spectrum: demonstration analyses in the COMPASS-ND study.

Research in aging, impairment, and Alzheimer's disease (AD) often requires powerful computational models for discriminating between clinical cohorts and identifying early biomarkers and key risk or protective factors. Machine Learning (ML) approaches represent a diverse set of data-driven tools for performing such tasks in big or complex datasets. We present systematic demonstration analyses to compare seven frequently used ML classifier models and two eXplainable Artificial Intelligence (XAI) techniques on multiple performance metrics for a common neurodegenerative disease dataset. The aim is to identify and characterize the best performing ML and XAI algorithms for the present data. We accessed a Canadian Consortium on Neurodegeneration in Aging dataset featuring four well-characterized cohorts: Cognitively Unimpaired (CU), Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI), and AD (N = 255). All participants contributed 102 multi-modal biomarkers and risk factors. Seven ML algorithms were compared along six performance metrics in discriminating between cohorts. Two XAI algorithms were compared using five performance and five similarity metrics. Although all ML models performed relatively well in the extreme-cohort comparison (CU/AD), the Super Learner (SL), Random Forest (RF) and Gradient-Boosted trees (GB) algorithms excelled in the challenging near-cohort comparisons (CU/SCI). For the XAI interpretation comparison, SHapley Additive exPlanations (SHAP) generally outperformed Local Interpretable Model agnostic Explanation (LIME) in key performance properties. The ML results indicate that two tree-based methods (RF and GB) are reliable and effective as initial models for classification tasks involving discrete clinical aging and neurodegeneration data. In the XAI phase, SHAP performed better than LIME due to lower computational time (when applied to RF and GB) and incorporation of feature interactions, leading to more reliable results.

Eyes-open and eyes-closed EEG of older adults with subjective cognitive impairment versus healthy controls: A frequency principal components analysis study.

Eyes-open and eyes-closed EEG of older adults with subjective cognitive impairment versus healthy controls: A frequency principal components analysis study.

Fibromyalgia and Rehabilitation. Not as You Thought. Changing the Stigma.

A cohort of patients in the rehabilitation wards also suffer from Fibromyalgia, which is considered the most prevalent cause of chronic pain. Poor function, subjective cognitive impairment, instability and imbalance are all common features of Fibromyalgia, among other more prominent features such as the use of chronic pain medication. The main purpose of this study was to examine the differences in Length of Stay (LOS) and functional outcome parameters. A retrospective cohort trial was conducted at the Soroka University Medical Centre. The time of data collection was conducted from January 2015 to December 2021. Patients were divided into two groups based on their exposure status: With Fibromyalgia (n=43) and Control group Without Fibromyalgia (n=1119). A 1:10 matching process and regression analysis were performed to avoid confounding factors. Matching was based on age, gender, and ethnicity. Various rehabilitation outcomes were collected along with pain assessment and pain medication use during the hospitalisation. Statistical analysis was performed using R software. A p value of<0.05 will be considered statistically significant. No statistically significant difference was found in the duration of hospitalisation, the FIM index at admission and discharge, or the change in the FIM index (ΔFIM) during hospitalisation between the two groups. No statistically significant differences were demonstrated in stability and balance indices (DGI, BBS) or cognitive assessment tests (MoCA). The stigma is incorrect, as patients with fibromyalgia can improve their functional parameters during an inpatient rehabilitation programme to the same degree as those without fibromyalgia.

Objectifying persistent subjective cognitive impairment following COVID-19 infection: cross-sectional data from an outpatient memory-clinic in Germany.

Subjective cognitive impairment is frequently reported by patients experiencing Post-COVID symptoms. This study aims to assess objective impairment in attention, memory, and executive functions among these patients. Further, we investigated potential determinants of objective cognitive impairment. In this cross-sectional study, standardized neuropsychological testing (Vienna Testing System), assessment of cognitive symptom aggravation, psychiatric anamnesis, and psychometrics (BDI-II, Fatigue Severity Scale) were conducted in 229 patients who voluntarily presented to our outpatient memory-clinic due to subjective cognitive impairment following COVID-19. Blood-samples were collected to assess peripheral immune markers (IL-6, CRP) and APOE-ε4 genotype. Objective cognitive impairment in at least one domain was present in 39% of the patients and 47% showed symptoms of moderate or severe depression. The APOE-ε4 allele was present in 32% of the patients. Higher rates of depressive symptoms (OR = 1.41, 95%-CI = 1.02-1.95) and higher burden of the APOE-ε4 allele (OR = 3.29, 95%-CI = 1.51-7.40) predicted objective cognitive impairment, regardless of age, sex, years of formal education, time since infection, and medication for diabetes or hypertension. Fatigue severity, acute COVID-19 severity or inflammation markers had no impact. In our study, subjective cognitive impairment following COVID-19 was more likely associated with high rates of depression rather than relatively low rates of objective cognitive performance. Thus, the study emphasizes the necessity for extensive neuropsychological testing and evaluation of depression when examining Post-COVID patients in clinical practice. Further, the link between objective cognitive impairment, depression and APOE-ε4 does not appear to be specific to Post-COVID symptoms. Therefore, depression- and APOE-ε4-mediated neurodegenerative pathomechanisms might be a promising therapeutical target.

Locus Coeruleus sexual dimorphism and its impact on cognitive impairment and cortical atrophy in Alzheimer's Disease.

Experimental data suggest sexual dimorphism in the Locus Coeruleus (LC), with females exhibiting higher neuronal count and noradrenergic activity. In Alzheimer's Disease (AD), progressive LC dysfunction may contribute early to pathogenesis, and female sex is a key risk factor for AD. This study aimed to investigate if such sex differences exist in humans and whether they influence the relationship between LC degeneration and AD features, such as cortical atrophy and cognitive decline. Fifty-three healthy controls (HC), 70 Mild Cognitive Impaired (MCI) subjects, and 29 Alzheimer's Disease Demented (ADD) patients underwent high-field brain MRI with LC-sensitive sequences following detailed neuropsychological and neurological assessments. LC integrity was measured using the LC Contrast Ratio (LCCR) parameter based on a previously published template approach. Within the HC and MCI groups, females showed higher LCCR values than males. A significant sex effect was observed in the relationship between LC integrity and cortical volume in the frontotemporal cortices, with males showing a stronger association. LC structure and function may differ between sexes, influencing AD pathophysiology through distinct mechanisms. While this sexual dimorphism may have a minor role, it should be considered in clinical investigations and drug development research.

HEaring and LIstening eXperience (HELIX): Evaluation of a co-designed serious game for auditory-cognitive training.

In the dementia field, a number of applications are being developed aimed at boosting functional abilities. There is an interesting gap as to how utilising serious games can further the knowledge on the potential relationship between hearing and cognitive health in mid-life. The aim of this study was to evaluate the auditory-cognitive training application HELIX, against outcome measures for speech-in-noise, cognitive tasks, communication confidence, quality of life, and usability. A randomised-controlled trial was completed for 43 participants with subjective hearing loss and/or cognitive impairment, over a play period of 4 weeks and a follow-up period of another 4 weeks. Outcome measures included a new online implementation of the Digit-Triplet-Test, a battery of online cognitive tests, and quality of life questionnaires. Paired semi-structured interviews and usability measures were completed to assess HELIX's impact on quality of life and usability. An improvement in the performance of the Digit-Triplet-Test, measured 4 and 8 weeks after the baseline, was found within the training group; however, this improvement was not significant between the training and control groups. No significant improvements were found in any other outcome measures. Thematic analysis suggested HELIX prompted the realisation of difficulties and actions required, improved listening, and positive behaviour change. Employing a participatory design approach has ensured HELIX is relevant and useful for participants who may be at risk of developing age-related hearing loss and cognitive decline. Although an improvement in the Digit-Triplet-Test was seen, it is not possible to conclude whether this was as a result of playing HELIX.

Neurovascular Decoupling Is Associated With Lobar Intracerebral Hemorrhages and White Matter Hyperintensities.

Neurovascular coupling is a fundamental aspect of brain function by regulating cerebral blood flow in response to regional neuronal activity. Increasing evidence suggest neurovascular decoupling occurs early in the progression of Alzheimer disease (AD), potentially reflecting early vascular damage. Therefore, understanding the relationship between neurovascular coupling and established vascular risk factors for AD is essential to gain deeper insights into the vascular mechanisms underlying AD. This cross-sectional observational study investigated the association between neurovascular coupling and vascular risk factors for AD, specifically small vessel disease magnetic resonance imaging markers, cardiovascular risk factors, and the apolipoprotein E genotype. The cohort included 119 participants diagnosed with subjective cognitive impairment, mild cognitive impairment, and AD-related dementia, as well as individuals without cognitive complaints. Neurovascular coupling was measured by blood-oxygen-level-dependent functional magnetic resonance imaging amplitude in response to visual stimulation. Our findings revealed that decreased neurovascular coupling is linked to structural brain changes typically seen in small vessel disease; specifically we found an association between neurovascular coupling and white matter hyperintensities load (β=-0.199, P=0.030) and presence of lobar intracerebral hemorrhage (β=-0.228, P=0.011). This raises the suggestion that a decreased neurovascular coupling in the disease process of AD is related to comorbid small vessel disease.

Subjective and functional cognitive impairment: diagnostics using biological markers of Alzheimer's disease

Cognitive impairment (CI) is one of the most common disorders in elderly. The development of dementia is usually preceded by subjective (SCI) and mild cognitive impairment (MCI) over several years. Patients with SCI are at increased risk of developing MCI and dementia, but SCI may not progress for a long time and in many cases is functional in nature (functional CI – FCI). The article discusses the manifestations and diagnostic issues of SCI and FCI and the possibilities of diagnosing Alzheimer's disease (AD) at the SCI stage using biological markers for AD in cerebrospinal fluid (CSF). The article presents the results of a long-term follow-up (more than 4 years) of two patients with SCI who showed no significant disturbances in repeated neuropsychological examinations. In one patient with SCI, positive biological markers for AD were found in the CSF, indicating an early (second) stage of AD, while in the other patient the absence of these markers indicated a functional nature of the CI. The article discusses the treatment of patients with SCI and the possibilities of anti-amyloid therapy when the Alzheimer's nature of CI is detected.

Tau-related reduction of glucose metabolism in mild cognitive impairment occurs independently of APOE ε4 genotype and is influenced by Aβ.

Positron emission tomography (PET) imaging studies have shown that amyloid beta (Aβ) is significantly correlated with glucose metabolism in mild cognitive impairment independently of the apolipoprotein E (APOE) ε4 genotype. We used a singular value decomposition (SVD) approach to pairwise cross-correlation among tau, Aβ, and fluorodeoxyglucose PET images. The resulting SVD-based tau and Aβ scores as well as the APOE ε4 genotype, were entered as predictors in a voxelwise general linear model for statistical assessment of their effect on FDG. We found cortical regions where a reduced glucose metabolism was maximally correlated with distributed patterns of tau, accounting for the effect of Aβ and APOE ε4 genotype. By highlighting the more significant role of tau, rather than Aβ, in the reduction of glucose metabolism, our results provide a better understanding of their combined effect in the development and progression of Alzheimer's disease. This study uses a data-driven singular value decomposition approach to the cross-correlation matrix between tau and fluorodeoxyglucose (FDG) images, as well as between FDG and amyloid beta (Aβ) positron emission tomography (PET) images. From a population of mild cognitive impairment subjects, we found that spatially distributed scores of tau PET are associated with an even stronger reduction of glucose metabolism, independent of the apolipoprotein E ε4 genotype and confounded by Aβ. By highlighting the more significant role of tau, rather than Aβ, on the reduction of glucose metabolism, our results provide a better understanding of their combined effects in the development of Alzheimer's disease.

Dual-task-related gait patterns as possible marker of precocious and subclinical cognitive alterations in Parkinson disease

Subtle gait and cognitive dysfunction are common in Parkinson’s disease (PD), even before most evident clinical manifestations. Such alterations can be assumed as hypothetical phenotypical and prognostic/progression markers. To compare spatiotemporal gait parameters in PD patients with three cognitive status: cognitively intact (PD-noCI), with subjective cognitive impairment (PD-SCI) and with mild cognitive impairment (PD-MCI) in order to detect subclinical gait differences. One hundred PD patients were consecutively enrolled and divided in three groups based on both the first item od MDS-UPDRS part I and an extensive neuropsychological evaluation: 41 PD-noCI, 15 PD-SCI and 44 PD-MCI. They were evaluated with gait analysis acquired in three different conditions (normal gait, motor and cognitive dual task). Spatiotemporal variables were extracted. A univariate statistical analysis (parametric ANOVA test or non-parametric Kruskal–Wallis test, as appropriate) with post-hoc analysis was carried out in order to evaluate the significant differences among the groups. In normal gait task, the three groups showed several differences, all due to the comparison between PD-MCI and PD-noCI, as disclosed by post-hoc analysis. In dual task conditions, mostly in the cognitive dual task, the three groups showed increased gait alterations that, at post-hoc analysis, mirrored the magnitude of cognitive dysfunction (PD-noCI < PD-SCI < PD-MCI). Peculiar prodromal gait patterns—especially those highlighted by cognitive dual task—could be considered possible markers to objectify self-reported symptoms-based construct, like SCI, and to early intercept subjects with different clinical evolutions and prognoses, even representing an innovative clustering/phenotyping tool for PD subtypes.

APOE4 impact on soluble and insoluble tau pathology is mostly influenced by amyloid-beta.

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). While APOE4 is strongly associated with amyloid-beta (Aβ), its relationship with tau accumulation is less understood. Studies evaluating the role of APOE4 on tau accumulation showed conflicting results, particularly regarding the independence of these associations from Aβ load. In this study, we examined three independent longitudinal cohorts (BioFINDER-1, BioFINDER-2 and WRAP) in which participants had cross-sectional and longitudinal measures of tau tangles (tau-PET; temporal meta-ROI and entorhinal) or soluble p-tau (p-tau217), Aβ-PET and APOE genotype. The study included a total of 1370 cognitively unimpaired (CU) and 449 mild cognitive impairment (MCI) subjects, followed longitudinally with tau-PET and p-tau217. APOE4 carriers accounted for 40.2-50% of the cohorts. Different linear regressions (cross-sectional) and linear mixed-effect models (longitudinal) with tau measures as outcomes were fitted to test the effect of APOE4 as independent predictor, as well as in combination with baseline Aβ load (including interaction). All models included age, sex and cognitive status as covariates. We found no independent effects of the APOE4 carriership on insoluble tau in either cohort (BioFINDER-2 or WRAP), both on cross-sectional and longitudinal tau-PET in the temporal meta-ROI, when Aβ was present in the model (p=0.531-0.949). Aβ alone was the best predictor of insoluble tau accumulation, with no interaction between APOE4 and Aβ on tau-PET. In BioFINDER-2, there was a significant interaction between APOE4 and Aβ (b=0.166, p<0.001) in the entorhinal cortex at baseline. However, the interaction was not present in WRAP PET. No independent effects of the APOE4 carriership on baseline (p=0.683-0.708) and longitudinal (p=0.188-0.570) soluble p-tau217 were observed when Aβ was included in the model in BioFINDER-1 and WRAP. Similarly, no interaction between APOE4 and Aβ on soluble p-tau217 was observed. Mediation analysis revealed that Aβ load fully mediated most associations between APOE4 and tau (46-112%, either cross-sectional or longitudinal tau-PET or soluble p-tau217). In the largest cohort (BioFINDER-2), looking at APOE4 groups by number of ε4 alleles, we found an interaction between APOE4 homozygotes and Aβ on tau-PET levels at baseline and over time in the temporal meta-ROI, while in the entorhinal cortex this effect was observed only at baseline. In conclusion, although APOE4 is strongly associated with Aβ aggregation, it seems to be minimally associated with longitudinal changes in soluble or insoluble p-tau levels at a given level of Aβ pathology, confirming the primacy of Aβ in driving tau pathology.

Quality of Life in Patients with Subjective Cognitive Impairment Referred to a Rural and Remote Memory Clinic.

We sought to compare whether quality of life (QOL) in patients with subjective cognitive impairment (SCI) who performed normally on a neuropsychological battery significantly differed from those diagnosed with mild cognitive impairment (MCI), Alzheimer's disease (AD) or non-Alzheimer's dementia (non-AD) at initial assessment in a Rural and Remote Memory Clinic (RRMC). 610 patients referred to our RRMC between 2004 and 2019 were included in this study. We compared self-reported and caregiver-reported patient QOL scores in those with SCI (n = 166) to those diagnosed with MCI (n = 98), AD (n = 228) and non-AD (n = 118). Patients with SCI self-reported significantly lower QOL compared to patients with AD. Interestingly, the reverse was seen in caregivers: SCI caregivers rated patient QOL higher than AD caregivers. Patients with SCI also reported lower QOL than patients with MCI. SCI caregivers reported higher patient QOL than their non-AD counterparts. Caregiver-rated patient QOL was higher in those with MCI compared to AD. Patients with MCI self-reported higher QOL scores compared to patients with non-AD dementias. Similarly, MCI caregivers reported higher patient QOL than non-AD caregivers. No other comparisons were statistically significant. Although they lacked clinically significant cognitive deficits, patients with SCI self-reported significantly lower QOL than patients with MCI and AD. Conversely, caregiver-reported patient QOL was higher for patients with SCI than for patients with AD and non-AD. This shows that SCI seriously impacts QOL. More research is needed on how we can better support patients with SCI to improve their QOL.

Association of small vessel disease progression with longitudinal cognitive decline across mild cognitive impairment.

Cerebral small vessel disease (SVD) is the leading cause of vascular dementia. However, it is unclear whether the individual SVD or global SVD progression correlates with cognitive decline across mild cognitive impairment (MCI) subjects. To investigate the association of small vessel disease progression with longitudinal cognitive decline across MCI. We included 432 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 151 participants in the cognitively normal (CN) group and 281 participants in the MCI group. We evaluated magnetic resonance imaging-based SVD markers in both CN and MCI groups and explored their associations with 12-and 24-month cognitive decline using linear mixing effect (LME) models. In the CN group, cerebral microbleed (CMB) progression was associated with the decline in language function (p < 0.05), and deep white matter hyperintensity (WMH) progression was associated with a decline in memory function (p < 0.05). In the MCI group, CMB progression was associated with a decline in memory function (p < 0.05) and lacunes progression was associated with executive function (p < 0.05), whereas the progression of global SVD score was not related to longitudinal cognitive function. The progression of CMB and WMH had an impact on cognitive decline in both CN and MCI groups, and lacunes progression only had an association with cognitive decline in the MCI group. Our study suggested that individual SVD markers may have a higher predictive value in longitudinal cognition compared with global SVD burden.

Tract-specific white matter hyperintensities and neuropsychiatric syndromes: a multicentre memory clinic study

BackgroundWhite matter hyperintensities (WMH) have been implicated in the pathogenesis of neuropsychiatric symptoms of dementia but the functional significance of WMH in specific white matter (WM) tracts is unclear. We...

Anticholinergic burden and behavioral and psychological symptoms in older patients with cognitive impairment.

Drugs with anticholinergic properties are frequently prescribed to patients with cognitive impairment. The cholinergic system plays an important role in learning processes, memory, and emotions regulation. The aim of this research is to report use of anticholinergic drugs in a clinical population and to investigate the correlation between the use of anticholinergic drugs and the risk of presenting with more severe behavioral and psychological symptoms (BPSD). Patients with a diagnosis of subjective cognitive impairment, mild cognitive impairment (MCI) or dementia were recruited. Screening tests for cognitive impairment (MMSE) and functional status (ADL, IADL) were performed. BPSD were evaluated with the Neuropsychiatric Inventory (NPI). The anticholinergic burden was calculated using the ACB calculator. We compared patients at low risk of anticholinergic adverse effects (ACB < 3) versus patients at high risk (ACB ≥ 3). Chi-square test and Mann-Whitney test were used to compare the two groups. A multiple linear regression was performed to identify factors associated with higher NPI score and a logistic regression model was built to identify drug classes associated with ACB ≥ 3. A total of 173 patients (mean age 74 ± 7, 74 men) were included in the study; 132 patients with ACB < 3 (low risk) versus 41 patients with ACB ≥3 (high risk) were compared. No statistically significant differences were found between the two groups in terms of demographics (age, sex) and anamnestic variables (education, marital status, family history of dementia, hypertension, diabetes, smoking, dyslipidemia, atrial fibrillation, coronary heart disease and use of alcohol). Significantly higher NPI scores were found in patients with ACB ≥ 3 (mean scores 47.3 ± 34.8 versus 25.5 ± 24.6, p < 0.001). Patients with ACB ≥ 3 showed lower MMSE (18.5 ± 8.6 versus 22.4 ± 7, p = 0.004) and more IADLs lost. In the multivariate regression analysis, after adjusting for age, sex, polypharmacy and IADLs lost, only the MMSE and the ACB scores were independent predictors of the NPI score. Being on antipsychotics, antidepressants and antidiabetic drugs was associated with increased risk of higher anticholinergic burden. In conclusion, the anticholinergic burden might play a significant role as a risk factor for developing more severe BPSD in patients with cognitive decline, independently from their degree of cognitive impairment.