Magnetic resonance imaging differences between dementia with Lewy bodies and Alzheimer's disease: a pilot study

BACKGROUND: Temporal lobe atrophy on magnetic resonance imaging (MRI) has been suggested as a specific diagnostic marker for Alzheimer's disease (AD). No previous comparison with dementia with Lewy bodies (DLB) has been reported. METHOD: T1-weighted MRI scans were performed on 11 subjects with AD (nine with NINCDS/ADRDA probable AD and two with neuropathologically proven AD) and nine subjects with DLB (four with probable DLB diagnosed by clinical criteria and five with neuropathologically proven DLB). Groups were matched for age, duration of illness and cognitive test score. Two raters, blind to diagnosis and neuropathological findings, measured the volumes of the frontal lobes, temporal lobes, hippocampi, parahippocampal gyri, amygdalae, and caudate nuclei using a computerized volumetric analysis system. Scans were also rated for medial temporal atrophy on a four-point scale by an experienced rater. RESULTS: AD subjects had significantly smaller left temporal lobes and parahippocampal gyri than those with DLB. Medial temporal atrophy was present in 9/11 AD cases (82%) and absent in 6/9 (67%) of DLB cases. Two neuropathologically confirmed cases of DLB had severe medial temporal atrophy; both had concurrent AD-type pathology in the temporal lobe (Braak stage 4). CONCLUSIONS: This pilot study supports the hypothesis that a greater burden of pathology centres on the temporal lobes in AD compared with DLB, except in DLB cases with concurrent Alzheimer pathology. A larger study is needed to confirm these findings and to determine whether MRI has a role in assisting with the clinical differentiation between DLB and AD.     

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD).OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS).RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.     

EEG findings in dementia with Lewy bodies and Alzheimer's disease

OBJECTIVES: To evaluate the role of the EEG in the diagnosis of dementia with Lewy bodies (DLB). METHODS: Standard EEG recordings from 14 patients with DLB confirmed at postmortem were examined and were compared with the records from 11 patients with Alzheimer's disease confirmed at postmortem RESULTS: Seventeen of the total of 19 records from the patients with DLB were abnormal. Thirteen showed loss of alpha activity as the dominant rhythm and half had slow wave transient activity in the temporal lobe areas. This slow wave transient activity correlated with a clinical history of loss of consciousness. The patients with Alzheimer's disease were less likely to show transient slow waves and tended to have less marked slowing of dominant rhythm. CONCLUSIONS: The greater slowing of the EEG in DLB than in Alzheimer's disease may be related to a greater loss of choline acetyltransferase found in DLB. Temporal slow wave transients may be a useful diagnostic feature in DLB and may help to explain the transient disturbance of consciousness which is characteristic of the disorder.     

Static balance improvement in elderly after dorsiflexors electrostimulation training

The purpose of the present study was to determine the effect of dorsiflexors ElectroStimulation (ES) training, on postural tasks of increasing difficulty in the elderly. Twenty-one elderly adults were randomly assigned into one of two groups: a Training (TG) and a Control Group (CG). The TG (n=10) performed (4 weeks, 4 s/week, 40 min/session) superimposed (electrically evoked and voluntary activation) isometric dorsiflexions (ankle 100°) while seated. Biphasic, rectangular symmetrical pulses (300 ms, 70 Hz, 20–60 mA) were used to provoke maximal muscle activation. Participants performed three static balance tasks (Normal Quiet Stance, Sharpened Romberg, and One-Legged Stance) during which postural sway was quantified using maximum range and standard deviation of Centre of Pressure displacement (Kistler 9281C, 1,000 Hz). Bipolar surface electrodes were used to record the Electromyographic activity (EMG) of Tibialis Anterior, Medial Gastrocnemius, Rectus Femoris and Semi-Tendineous. Two-dimensional kinematic data were collected (60 Hz) and analyzed using the APAS Motion Analysis software. The body was modeled as a five-segment rigid link system. Isometric dorsiflexion moment/angular position relationship was also established using a Cybex dynamometer. ES training resulted in decreased postural sway (P<0.05), greater ankle muscles EMG activity (P<0.001), greater stability of the ankle joint (P<0.05) and significant changes in mean position of all three joints of the lower limb. In addition, dorsiflexion moment significantly (P<0.001) increased as a result of ES training. It is concluded that dorsiflexors ES training, could reduce postural sway and the use of ankle muscles, more characteristic of young adults, might appear in the elderly as well.     

Immunohistochemical evaluation of TGF-β and extracellular matrix proteins expression in rat squamous cell carcinomas

OBJECTIVE: The aim of this study was to establish a possible association between the degree of differentiation of squamous cell carcinomas (SCC) derived from rat oral tissues treated in vivo with the carcinogen 4NQO, and the expression of TGF-β on epithelial cells and the distribution of extracellular matrix proteins (laminin-collagen type IV).
MATERIALS AND METHODS: A parent tumour showing a spectrum of differentiation was used to establish clonal subpopulations that formed differentiated SCC and undifferentiated (spindle cell phenotype) tumours following transplantation to athymic mice.
RESULTS tmmunohistological findings revealed the absence of TGF-β staining on epithelial cells and extracellular matrix proteins in spindle cell tumours. In contrast, staining of SCC revealed a significant number of TGF-β positive cells and the presence of extracellular matrix proteins.
CONCLUSIONS: The findings suggested that there is a positive correlation between histological differentiation, TGF-β expression and the elaboration of extracellular matrix proteins.     

Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implications for semiquantitative comparative histology

A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.      

Defining the Riddle in Order to Solve It: There Is More Than One “Parkinson's Disease”

Background

More than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central nervous system such as dementia, motor neuron disease, multiple sclerosis, and epilepsy. Clinicians, pathologists, and basic science researchers evolved arrange of concepts andcriteria for the clinical, genetic, mechanistic, and neuropathological characterization of what, in their best judgment, constitutes PD. However, these specialists have generated and used criteria that are not necessarily aligned between their different operational definitions, which may hinder progress in solving the riddle of the distinct forms of PD and ultimately how to treat them.

Objective

This task force has identified current in consistencies between the definitions of PD and its diverse variants in different domains: clinical criteria, neuropathological classification, genetic subtyping, biomarker signatures, and mechanisms of disease. This initial effort for “defining the riddle” will lay the foundation for future attempts to better define the range of PD and its variants, as has been done and implemented for other heterogeneous neurological syndromes, such as stroke and peripheral neuropathy. We strongly advocate for a more systematic and evidence-based integration of our diverse disciplines by looking at well-defined variants of the syndrome of PD.

Conclusion

Accuracy in defining endophenotypes of “typical PD” across these different but interrelated disciplines will enable better definition of variants and their stratification in therapeutic trials, a prerequisite for breakthroughs in the era of precision medicine. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.