Thais Minett

Extrapyramidal features in Parkinson’s disease with and without dementia and dementia with Lewy bodies: A cross-sectional comparative study

Risk factors predicting an increased risk of dementia in Parkinsons disease (PD) are not fully established. The dementia associated with PD (PDD) closely resembles dementia with Lewy bodies (DLB). Based upon a high frequency of non‐dopaminergic mediated clinical features in DLB, we predicted that a motor subtype comprising postural instability and balance problems would be more common in PDD. We examined extrapyramidal, cognitive, and affective features in 38 PD, 43 PDD, and 26 DLB patients in a cross‐sectional study design. Motor subtype was subdivided into postural‐instability gait difficulty (PIGD) or tremor (TD) dominant. The PIGD‐subtype was more common in PDD (88% of cases) and DLB (69% of cases) groups compared with the PD group (38% of cases), in which TD and PIGD sub‐types were more equally represented (P < 0.001). Although the mean depression scores overall were modest, PDD patients scored significantly higher than PD, but not DLB patients (Cornell; P = 0.006, and Geriatric Depression scale, GDS‐15; P = 0.001), while within the PD group, those patients with a PIGD subtype had greater depression scores than the TD subtype (GDS‐15; P < 0.05). We conclude that non‐dopaminergic motor features are frequent in PDD. Neurodegeneration within the cholinergic system is likely to mediate many of these motor problems, as well as playing a significant role in determining the neuropsychiatric symptomatology of both PDD and DLB.

Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients

OBJECTIVES Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. METHODS This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. RESULTS Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. CONCLUSIONS Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression.

Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review

Objective To describe how criteria for amnestic Mild Cognitive Impairment (aMCI) have been operationalised in randomised controlled clinical trials (RCTs). Design Systematic review. Information sources EMBASE, PubMed and PSYCHInfo were searched from their inception to February 2012. Electronic clinical trial registries were also searched (February 2012). Study selection RCTs were included where participant selection was made using Petersen et al-defined aMCI. There was no restriction on intervention type or the outcome tested. Data extraction For each trial, we extracted information on study design, demographics, exclusion criteria and the operationalisation strategy for the five aMCI diagnostic criteria including: (1) memory complaint, (2) normal general cognitive function, (3) memory impairment, (4) no functional impairment and (5) no dementia. Results 223 articles and 278 registered trials were reviewed, of which 22 met inclusion criteria. Various methods were applied for operationalising aMCI criteria resulting in variability in participant selection. Memory complaint and assessment of general cognitive function were the most consistently measured criteria. There was large heterogeneity in the neuropsychological methods used to determine memory impairment. It was not possible to assess the impact of these differences on case selection accuracy for dementia prediction. Further limitations include selective and unclear reporting of how each of the criteria was measured. Conclusions The results highlight the urgent need for a standardised approach to map aMCI. Lack of uniformity in clinical diagnosis, however, is not exclusively a problem for MCI but also for other clinical states such as dementia including Alzheimers disease, Lewy Body, frontotemporal or vascular dementia. Defining a uniform approach to MCI classification, or indeed for any classification concept within the field of dementia, should be a priority if further trials are to be undertaken in the older aged population based on these concepts.

Changes in DWI and MRS associated with white matter hyperintensities in elderly subjects

Objective: To assess normal-appearing white matter (NAWM) characteristics by magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in elderly subjects. Methods: The authors studied 60 volunteers (mean age 72.6 years; SD 4.7; range 64 to 84 years) without signs of neurologic illness. They used DWI and spectroscopic imaging to investigate whether there were changes in the NAWM that related to the presence of white matter hyperintensities (WMH). Results: The authors found a correlation (p < 0.001) between the apparent diffusion coefficient in the NAWM and the total volume of WMH. The metabolite ratios N-acetylaspartate/creatine and N-acetylaspartate/choline of the NAWM also correlated significantly with total WMH volume. These correlations were independent of age. Conclusions: Damage associated with WMH is detectable in NAWM.

Microlinguistic aspects of the oral narrative in patients with Alzheimer's disease.

BACKGROUND Alzheimers disease (AD) is characterized by memory loss and cognitive impairment. Phonological, syntactic, semantic and discursive aspects of language may also be affected. Analysis of micro- and macrolinguistic abilities of discourse may assist in diagnosing AD. The aim of this study was to identify changes in the discourse (lexical errors and syntactic index) of AD patients. METHODS 121 elderly subjects narrated a story based on a seven-figure picture description. RESULTS Patients with AD presented more word-finding difficulties, revisions and repetitions, and the syntactic index was lower than controls. CONCLUSION Performance in microlinguistics at the lexical and syntactic levels was lower than expected in participants with AD.

Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Skin biopsy in Lafora disease Genotype–phenotype correlations and diagnostic pitfalls

Lafora disease is characterized by pathognomonic inclusions, Lafora bodies (LB), in neurons and other cell types. In skin, LB have been reported in either eccrine sweat glands or in apocrine sweat glands. The disease is caused by mutations in either the EPM2A gene or in a second yet-unknown gene. Here the authors determine whether a genotype–phenotype correlation exists between the genetic form of the disease and the skin cell type affected by LB formation. Also is described an important source of false positivity in the use of axillary biopsies for disease diagnosis.

Performance of normal adults on Rey Auditory Learning Test: a pilot study

The present study aimed to assess the performance of healthy Brazilian adults on the Rey Auditory Verbal Learning Test (RAVLT), a test devised for assessing memory, and to investigate the influence of the variables age, sex and education on the performance obtained, and finally to suggest scores which may be adopted for assessing memory with this instrument. The performance of 130 individuals, subdivided into groups according to age and education, was assessed. Overall performance decreased with age. Schooling presented a strong and positive relationship with scores on all subitems analyzed except learning, for which no influence was found. Mean scores of subitems analyzed did not differ significantly between men and women, except for the delayed recall subitem. This manuscript describes RAVLT scores according to age and education. In summary, this is a pilot study that presents a profile of Brazilian adults on A1, A7, recognition and LOT subitem.

Microglial immunophenotype in dementia with Alzheimer's pathology

BackgroundGenetic risk factors for Alzheimer’s disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes.MethodsUsing the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer’s pathology. Cerebral cortex obtained at post-mortem from 299 participants was analysed by immunohistochemistry for cluster of differentiation (CD)68 (phagocytosis), human leukocyte antigen (HLA)-DR (antigen-presenting function), ionized calcium-binding adaptor molecule (Iba1) (microglial motility), macrophage scavenger receptor (MSR)-A (plaque-related phagocytosis) and CD64 (immunoglobulin Fcγ receptor I).ResultsThe presence of dementia was associated positively with CD68 (P < 0.001), MSR-A (P = 0.010) and CD64 (P = 0.007) and negatively with Iba1 (P < 0.001). Among participants without dementia, the cognitive function according to the Mini-Mental State Examination was associated positively with Iba1 (P < 0.001) and negatively with CD68 (P = 0.033), and in participants with dementia and Alzheimer’s pathology, positively with all microglial markers except Iba1. Overall, in participants without dementia, the relationship with Alzheimer’s pathology was negative or not significant, and positive in participants with dementia and Alzheimer’s pathology. Apolipoprotein E (APOE) ε2 allele was associated with expression of Iba1 (P = 0.001) and MSR-A (P < 0.001) and APOE ε4 with CD68, HLA-DR and CD64 (P < 0.001).ConclusionsOur findings raise the possibility that in dementia with Alzheimer’s pathology, microglia lose motility (Iba-1) necessary to support neurons. Conversely, other microglial proteins (CD68, MSR-A), the role of which is clearance of damaged cellular material, are positively associated with Alzheimer’s pathology and impaired cognitive function. In addition, our data imply that microglia may respond differently to Aβ and tau in participants with and without dementia so that the microglial activity could potentially influence the likelihood of developing dementia, as supported by genetic studies, highlighting the complexity and diversity of microglial responses.

C-reactive protein, APOE genotype and longitudinal cognitive change in an older population

Background: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. Methods: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. Results: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. Conclusions: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population.