Effects of statins over clinical changes in Alzheimer’s disease (AD) are usually non-significant, but epistatic interactions between genetic variants involved in cholesterol metabolism could be ...important for such effects. We aimed to investigate whether
LDLR
single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also considering
APOE
haplotypes and lipid-lowering treatment with lipophilic statins for stratification. Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and caregiver burden, with prospective neurotranslational correlations documented for 1 year. For 179 patients, minor allele frequencies were 0.078 for rs11669576–A (14.5% heterozygotes), 0.346 for rs5930–A (42.5% heterozygotes), and 0.444 for rs5925–C (56.4% heterozygotes), all in Hardy-Weinberg equilibrium; 134 patients had hypercholesterolemia, and 133 used lipophilic statins. Carriers of rs11669576–G had faster cognitive decline, while functional decline was slower for carriers of rs11669576–A who used lipophilic statins.
APOE
-ε4 carriers who also carried rs5930–AA had improved caregiver burden, while carriers of haplotypes that included rs5930–AG had worse cognitive and functional outcomes, though carriers of the A allele of rs5930 had better cognitive and functional response to lipophilic statins.
APOE
-ε4 non-carriers who carried rs5925–TT had slower cognitive decline, while lipophilic statins protected carriers of the other genotypes. We preliminarily conclude that reportedly protective variants of
LDLR
and
APOE
against risk of AD also slowed cognitive decline, regardless of cholesterol variations, while therapy with lipophilic statins might benefit carriers of specific genetic variants.
Pharmacogenetic effects of statins on clinical changes in Alzheimer's disease (AD) could be mediated by epistatic interactions among relevant genetic variants involved in cholesterol metabolism.
To ...investigate associations of HMGCR (rs3846662), NR1H2 (rs2695121), or CETP (rs5882&rs708272) with cognitive and functional changes in AD, with stratification according to APOEɛ4 carrier status and lipid-lowering treatment with lipophilic statins.
Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and global ratings, with prospective neurotranslational associations documented for one year.
Considering n = 190:142 had hypercholesterolemia, 139 used lipophilic statins; minor allele frequencies were 0.379 (rs2695121-T:46.3% heterozygotes), 0.368 (rs5882-G:49.5% heterozygotes), and 0.371 (rs708272-A:53.2% heterozygotes), all in Hardy-Weinberg equilibrium. For APOEɛ4 carriers: rs5882-GG protected from cognitive decline; rs5882-AA caused faster cognitive decline; carriers of rs2695121-CC or rs5882-AA were more susceptible to harmful cognitive effects of lipophilic statins; carriers of rs5882-GG or rs708272-AG had functional benefits when using lipophilic statins. APOEɛ4 non-carriers resisted any cognitive or functional effects of lipophilic statins, while invariability of rs3846662 (all AA) prevented the assessment of HMGCR effects. When assessing CETP haplotypes only: rs5882-GG protected from cognitive and functional decline, regardless of lipophilic statin therapy; lipophilic statins usually caused cognitive and functional harm to carriers of rs5882-A and/or rs708272-A; lipophilic statins benefitted cognition and functionality of carriers of rs5882-G and/or rs708272-G.
Reportedly protective variants of CETP and NR1H2 also slowed cognitive and functional decline particularly for APOEɛ4 carriers, and regardless of cholesterol variations, while therapy with lipophilic statins might affect carriers of specific genetic variants.
•Predictors of Lewy body dementia onset differ from other neurodegenerative diseases.•Night-time behavior disturbances are inversely associated with sleep satisfaction.•Caregiver burden is more ...affected by depression and motor features.•Non-motor symptoms are more burdensome for patients with dementia with Lewy bodies.•In Parkinson’s disease dementia, anxiety and dysphoria arise when motor features are less burdensome.
Differential diagnosis between Parkinson’s disease (PD) dementia and dementia with Lewy bodies (DLB) is difficult due to common features, whereas management decisions and research endpoints depend upon knowledge of dementia severity. We aimed to assess risk factors for age at dementia onset, as well as which neuropsychiatric features are associated with pharmacotherapy and signs and symptoms of Lewy body dementia.
Patients with PD dementia or DLB were evaluated for age at disease onset, education, sanitation, anthropometric measures, alcohol use, smoking, history of infections or head trauma with unconsciousness, family history of neurodegenerative diseases, functional independence, cognition, behavior, motor features, caregiver burden and pharmacotherapy.
Fifty-one patients were recruited (37 with DLB, 14 with PD dementia). Cumulative alcohol use and married status were associated with earlier dementia onset, whereas history of treated systemic infections and cumulative family history of primary neurodegenerative diseases led to later dementia onset. The length of dementia was shorter only for severely impaired patients who used anti-depressants, but not for users of cholinesterase inhibitors, while no behavioral symptom was associated with dopaminergic therapy. Night-time behavior disturbances were inversely associated with sleep satisfaction, while caregiver burden was more affected by depression and motor features. Non-motor symptoms were more burdensome for patients with DLB, while in PD dementia anxiety and dysphoria occurred when motor features were less burdensome.
PD dementia and DLB are two phenotypes of the same pathological entity, differing mostly by the occurrence of parkinsonian signs. Predictors of dementia onset differ from other neurodegenerative diseases.
Lifetime risk factors for cognitive and functional decline in Alzheimer's disease (AD) are not fully understood, and were prospectively evaluated in patients with low mean schooling from São Paulo, ...Brazil. Consecutive outpatients with late-onset AD were assessed for APOE haplotypes and the following potential baseline predictors: gender, schooling, age at dementia onset, lifetime urban living and sanitary conditions, occupational complexity, cognitive and physical activities, cerebrovascular risk factors (obesity, lifetime alcohol use and smoking, length of arterial hypertension, diabetes mellitus, and a dyslipidemic profile), use of a pacemaker, creatinine clearance, body mass index, waist circumference, head traumas with unconsciousness, treated systemic bacterial infections, amount of surgical procedures under general anesthesia, and family history of AD. Participants were followed from October 2010 to May 2017 for baseline risk factor associations with time since dementia onset for Clinical Dementia Rating and Mini-Mental State Examination score changes. For 227 patients (154 women, 119 APOE ε 4 carriers), later AD onset (mean 73.60±6.4 years-old, earlier for APOE ε 4/ε 4 carriers, p < 0.001) was the only variable hastening all endpoints, baseline creatinine clearance and lifetime alcohol use were hazardous for earlier cognitive and functional endpoints, women had earlier cognitive endpoints only, and schooling had a cumulative protective effect over later cognitive endpoints, particularly for carriers of APOE ε 4. Exclusively for carriers of APOE ε 4, head traumas with unconsciousness were hazardous for earlier cognitive endpoints, while lifetime sanitary conditions were protective regarding later cognitive endpoints. Functional and cognitive outcomes in AD represent probable interactions between effects of brain reserve and cerebral perfusion over neurodegeneration.
Cognitive Impairment in Fibromyalgia Bertolucci, Paulo Henrique Ferreira; de Oliveira, Fabricio Ferreira
Current pain and headache reports,
07/2013, Volume:
17, Issue:
7
Journal Article
Peer reviewed
Cognitive and behavioral impairments are core manifestations of fibromyalgia and may be more disabling than pain itself. Involvement of the central nervous system is ascertained by the fact that ...frontoparietal and limbic cortices are often functionally and structurally affected along the course of this disease. Even though neuroimaging has brought some experimental evidence to support such network disruption, there are currently no clinically effective biomarkers that detect and quantify cognitive and behavioral disturbances in fibromyalgia; thus, traditional scales and tests of neuropsychiatric assessment remain the most important diagnostic tools. This review addresses the most common cognitive and behavioral impairments in people with fibromyalgia, while explaining their pathophysiological basis and currently available therapeutic options.
ABSTRACTIntroduction:Alzheimer's disease (AD) is a degenerative syndrome that impairs cognitive functioning, including speech and language. Discourse can be used to analyze language processing, which ...is organized into microlinguistic and macrolinguistic dimensions.
To identify the occurrence of changes in the macrolinguistic dimension of oral discourse in AD patients.
This was developed as a cross-sectional study.
Outpatient clinic of the Behavioural Neurology Division of São Paulo Federal University.
121 elderly patients, with ≥ 4 years of education, divided into AD and comparison groups.
The subjects were asked to create a narrative based on seven figures that made up a story. The macrolinguistic aspects of the narratives were analyzed.
The performance of the AD group was inferior to that of the comparison group on content-related, no-content-related complete and incomplete propositions as well as macropropositions, main information units, appropriated local and global coherence, cohesive devices and all subtypes, cohesive errors and some of their subtypes. Global coherence, macropropositions and ellipsis subtype of cohesive devices were the variables that best differentiated the groups.
Changes were observed in most aspects of the macrolinguistic dimension of oral discourse in patients with AD.
•Cognitive impairments in multiple system atrophy.•Neuropsychological tests to compare cognitive dysfunction between two types of multiple system atrophy: MSA-P and MSA-C.•Cognitive impairment in ...multiple system atrophy patients with or without postural hypotension.
We evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C).
This cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinson’s disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI). Neuropsychological tests were used to evaluate general cognition, verbal and visual memory, working memory, constructional ability, visuospatial, language, and executive function.
The median age of the patients was 62 years, median disease duration was 3.5 years, and median education level was 10 years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the continuous data between the two MSA subtypes and observed that bodily pain reported in the quality of life questionnaire, SF-36, was worse in MSA-P (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA-C than MSA-P (p<0.05).
Our comparative study of cognitive impairment in MSA-P and MSA-C showed that both groups had impaired executive and visuospatial functions, while the attention deficit was predominant only in MSA-C. These findings support the concept that cognitive deficit originates from striatofrontal dysfunction and cerebellar degeneration. Our study also suggests that cognitive impairment is relevant in MSA, and clinical neurologists should not neglect evaluation of these aspects in their daily clinical practice.
Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer's disease, but the types of naming errors and the ways in which this deficit changes over the course of the ...disease are unclear. We analyzed the performance of patients with Alzheimer's disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease.
A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer's disease, 30 patients with moderate Alzheimer's disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors.
The patients with moderate Alzheimer's disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer's disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer's disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors.
Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing.
ABSTRACT
Background:
During the moderate stage of dementia due to Alzheimer’s disease (AD), language disorder is more evident and it impacts on communication. An overview of language impairment could ...be helpful to find compensatory communication strategies for these patients.
Objective:
To identify all language impairments among patients with moderate-stage of AD.
Methods:
20 patients diagnosed with probable AD based on the criteria of the NINCDS-ARDRA, with a MMSE score of 13-23 points and CDR=2, who were undergoing treatment for AD with therapeutic doses of acetyl cholinesterase inhibitors, were assessed using the Boston Diagnostic Aphasia Examination (BDAE), a test that provides a broad assessment of language. The results were compared with the performance of a normal population.
Results:
The patients assessed in this study presented normal scores for oral and written word recognition, repetition, mechanics of writing, primer-level dictation and spelling to dictation but also had impairment at most levels of linguistic processing, in oral and written comprehension and production. In general, as expected, the tasks relying on access to the mental lexicon were most significantly affected. However, they performed well in the naming task, in which semantic cues were presented. Moreover, the patients assessed in this study had better performance in written comprehension tasks than in oral ones.
Conclusion:
The severity of the language impairments was not homogenous, with some linguistic abilities more impaired than others. The abilities that were found to be preserved can help to guide strategies for aiding in communication at this stage of AD.
Introduction: The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of APOE and ACE with age at AD onset and with ...neuropsychiatric symptoms according to each dementia stage.
Methods: Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 (APOE haplotypes, Real-Time Polymerase Chain Reactions), and the ACE insertion/deletion polymorphism (Polymerase Chain Reactions). Combined genetic variants of APOE and ACE were associated with age at dementia onset, and with neuropsychiatric symptoms in each dementia stage (adjusted for sex and age at dementia onset).
Results: Over two-thirds of the 238 patients were women, whereas the mean age at dementia onset was 73.82 ± 6.2 years-old. APOE-ϵ4/ϵ4 carriers had earlier dementia onset (p<.001). The ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p=.37) but was not associated with age at dementia onset, regardless of APOE-ϵ4 carrier status. The only results that survived corrections for false discovery rates were higher scores of dysphoria for APOE-ϵ4 carriers (n=122) who also carried ACE deletion/deletion (p=.031). No results survived corrections for false discovery rates for APOE-ϵ4 non-carriers (n=116).
Conclusions: Though only the APOE-ϵ4/ϵ4 haplotype affected AD onset, effects of the ACE insertion/deletion polymorphism over behavioural features might differ according to APOE-ϵ4 carrier status in genetic associations.
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