Abstract
Objective
The immediate copy of the Rey–Osterrieth Complex Figure (ROCF) is considered a visuo-spatial test. However, reproducing this complex structure possibly involves also executive ...functions, such as planning and organizational strategies. In a previous study, we found a high rate of impaired performances in this test in a sample of subcortical vascular mild cognitive impairment patients. Executive functions contribution in the immediate copy of the ROCF can be assessed with the Boston Qualitative Scoring System (BQSS). We aimed at examining whether BQSS executive scores of ROCF immediate copy: (1) differ between vascular (v-MCI) and degenerative MCI (d-MCI) patients; (2) can at least partly explain the high rate of abnormal ROCF immediate copy performances in v-MCI patients.
Method
Thirty d-MCI patients (age 75.2 ± 4.4) and 27 v-MCI (age 73.2 ± 6.9) were enrolled. The performances of patients were scored using the BQSS executive scores (Fragmentation, Planning, Organization, Perseveration) during the accomplishment of ROCF immediate copy.
Results
Comparing d-MCI and v-MCI performances, d-MCI patients scored worse on ROCF delayed recall (9.9 ± 4.7 vs. 13.4 ± 5.9, p = .020) and MMSE (23.9 ± 2.6 vs. 27.8 ± 2.3, p = .001) while v-MCI patients had more frequently impaired performances in ROCF immediate copy (40% vs. 81%, p = .001) and showed worse scores on Fragmentation (2.4 ± 0.9 vs. 1.8 ± 1.3, p = .035), Planning (2.4 ± 0.8 vs. 1.8 ± 1, p = .039), Organization (4.8 ± 1.3 vs. 3.6 ± 2.1, p = .017), and Perseveration (3.5 ± 0.8 vs. 2.9 ± 1.2, p = .048).
Conclusions
The performance of v-MCI patients in ROCF immediate copy seemed to be more affected by executive dysfunction than the performance obtained by d-MCI. When analyzing ROCF performances, a qualitative approach allows to evaluate patients’ strategies during the reproduction, and thus to discriminate between executive and visuo-constructional abilities.
Trimethylamine-
-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of ...many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer's disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study.
HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell ...cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD (n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects (n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apoε4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (−73% and −33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (−40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (−24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoε4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 (r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau (r = −0.348, P = 0.018 and r = −0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD.
The treatment of Alzheimer’s disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) ...represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning.
The present study provides important hints on the promising therapeutic use of rTMS in AD.
•rTMS enhanced the effect of face-name associative memory cognitive training.•The add-on rTMS effect was influenced by disease severity and education.•rTMS amelioration generalized to visuospatial reasoning.
Considerable evidence suggests a close relationship between vascular and degenerative pathology in the human hippocampus. Due to the intrinsic fragility of its vascular network, the hippocampus ...appears less able to cope with hypoperfusion and anoxia than other cortical areas. Although hippocampal blood supply is generally provided by the collateral branches of the posterior cerebral artery (PCA) and the anterior choroidal artery (AChA), different vascularization patterns have been detected postmortem. To date, a methodology that enables the classification of individual hippocampal vascularization patterns in vivo has not been established. In this study, using high-resolution 7 Tesla time-of-flight angiography data (0.3 mm isotropic resolution) in young adults, we classified individual variability in hippocampal vascularization patterns involved in medial temporal lobe blood supply in vivo. A strong concordance between our classification and previous autopsy findings was found, along with interesting anatomical observations, such as the variable contribution of the AChA to hippocampal supply, the relationships between hippocampal and PCA patterns, and the different distribution patterns of the right and left hemispheres. The approach presented here for determining hippocampal vascularization patterns in vivo may provide new insights into not only the vulnerability of the hippocampus to vascular and neurodegenerative diseases but also hippocampal vascular plasticity after exercise training.
•First attempt to classify human hippocampal vascularization in vivo using 7Tesla Angiography•Good concordance between in vivo findings and autopsy studies•A new avenue to investigate interindividual variability in hippocampal vascular plasticity•A new avenue for linking individual vascular anatomical phenotypes to neurodegenerative and vascular pathology
Visuo-constructive abilities are a multicomponential process that can be impaired in several neurodegenerative dementias. Among visuo-constructive tasks, the Rey-Osterrieth Complex Figure-copy ...(ROCF-c) is the most commonly used and it seems influenced by different skills mediated by specific brain regions. This task complexity allows exploring differential mechanisms of impairment in different neurodegenerative disorders. In this study we examined the neuroanatomical substrates of ROCF-c performance in patients with Dementia with Lewy Bodies (DLB) and patients with Alzheimer’s disease (AD). We included forty-five patients with probable DLB, and thirty-four patients with probable typical-AD. To identify the ROCF-c scores neural correlates we performed a regression analysis with brain hypometabolism using the ROCF-c scores as independent variable. Then we evaluated the correlation between regional hypometabolism and ROCF-c scores in each group separately, throughout offline Pearson correlation analysis. The DLB and AD groups differed only in visuo-constructive and memory performances. DLB patients performed worse at the visuo-constructive test, while typical-AD patients performed worse at the verbal memory task. In DLB, worse performance at ROCF-c scores (more severe visuo-constructive impairment) correlated with occipital and temporo-parietal hypometabolism. In AD, worse performance at ROCF-c score was associated with brain hypometabolism in the temporo-parietal regions. The inability to correctly perform the ROCF-c derives from distinct brain dysfunctions in DLB and AD. The present results suggest alterations in visuoperceptual processes due to the severe occipital hypometabolism in DLB, and in visuospatial processes related to temporo-parietal hypometabolism in AD.
Abstract
Background
Loneliness is a major health issue among older adults. The aim of this study was to assess the relationship between loneliness, in its social and emotional facets, and the ...cognitive (language), and behavioral/psychological functioning as well as quality of life (QoL) in people with mild and moderate dementia, i.e., considering dementia severity as an individual characteristic.
Methods
This cross-sectional study involved 58 people with mild dementia and 55 people with moderate dementia. Participants completed the Social and Emotional Loneliness scale, along with measures assessing their language skills, the frequency and severity of their behavioral and psychological symptoms, and their QoL.
Results
Socio-demographic characteristics and depression, but not loneliness or its social and emotional facets, contributed to explain participants’ behavioral and psychological symptoms, regardless of dementia severity. Loneliness explained, though to a small extent (8% of variance), language skills in people with moderate dementia, with social loneliness only accounting for language skills (18% of variance) in this group. Loneliness also modestly accounted for dysphoria symptoms in both the mildly and moderately impaired (6% and 5% of variance, respectively) individuals with social loneliness predicting dysphoric mood in the former group only (7% of variance). Loneliness also explained, to a larger extent, QoL in both the mildly impaired and moderately impaired individuals (27% and 20% of variance, respectively), its social facet predicting QoL in the mildly impaired (30% of variance), and its emotional facet in the moderately impaired (21% of variance) group.
Conclusion
These findings suggest that loneliness and its facets have a clear impact on perceived QoL, and influence the language skills and dysphoria symptoms of people with dementia, to a degree that depends on dementia severity. The assessment of loneliness and its facets in people with dementia considering dementia severity, and the promotion of social inclusion to reduce it should be considered by professionals.
Alzheimer's disease (AD) has been associated with dysregulation of brain cholesterol trafficking and abnormal production of apolipoprotein E isoform 4 (apoE4). Proprotein convertase subtilisin/kexin ...type 9 (PCSK9) is a protein present in serum and cerebrospinal fluid (CSF) degrading the low-density lipoprotein receptor (LDLr) and other apoE-binding receptors involved in neuron cholesterol uptake. The role of PCSK9 in AD is controversial.
We compared PCSK9 levels in CSF of AD patients and non-AD controls and looked at correlations with CSF total apoE and apoE4.
CSF from AD (n = 30) and from age and sex-matched non-AD patients (n = 30) was collected by lumbar puncture for routine diagnosis. CSF PCSK9, total apoE, and apoE4 levels were measured by ELISA. AD patients showed the typical CSF neurobiomarker pattern (decreased Aβ42 and increased tau and phospho-tau) and impaired cognitive performances, as indicated by the scores of the Mini-Mental State Examination test.
PCSK9 levels in CSF were higher in AD than in non-AD subjects (+1.45 fold; p = 0.0049). CSF total apoE concentrations did not differ between the two groups, while apoE4 levels were higher in AD subjects (+3.34 fold; p = 0.0068). Considering all samples, a significant positive correlation was found between PCSK9 and apoE4 (r = 0.4409; p = 0.0006). PCSK9 levels were higher in APOE ɛ4 carriers, reaching statistical significance in the AD group (+1.45 fold; p = 0.0454).
These results report for the first time an alteration of CSF PCSK9 levels in AD and suggest a pathophysiological link between PCSK9, apoE4, and AD.
The rate of cognitive and functional decline in Alzheimer's disease (AD) changes across individuals.
Our purpose was to assess whether the concept of "fast decline" really fits its definition and ...whether cognitive and functional variables at onset can predict the progression of AD.
324 AD patients were included. We retrospectively examined their Mini-Mental State Examination (MMSE) total score and sub-items, Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) at baseline and every six months for a 4-year follow-up. Patients were divided into "fast decliners" (n = 62), defined by a loss ≥5 points on the MMSE score within the first year from the baseline; "intermediate decliners" (n = 37), by a loss ≥5 points after the first year and before the 18th month; or "slow decliners" (n = 225), composed of the remaining patients.
At baseline, the groups did not differ on demographic, clinical, and cognitive variables. The decline at the end of the 4-year follow-up period seems to be similar among the different decline clusters. Predictors of disease progression have not been identified; only the MMSE total score at 12 months <14/30 was indicative of a poor prognosis.
Even with the limitation due to the small sample size, the lack of differences in the disease progression in time in the different clusters suggest the inconsistency of the so-called "fast decliners". This study was unable to show any significant difference among clusters of AD progression within a 4-year time interval. Further studies should better clarify whether a more consistent distinction exists between slow and fast decliners.
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