Apraxia and dementia severity in Alzheimer's disease: a systematic review.

INTRODUCTION: To investigate the role and influence of apraxia regarding dementia severity in Alzheimer's disease (AD). In addition, to examine whether apraxia or its association to dementia severity show distinct characteristics between typical and atypical variants of AD, that commonly include frontal, logopenic, posterior, and Down's syndrome variant. METHOD: The search conducted on 4 December 2020 in the Cinahl, Ovid Medline, PsycArticles, PsycInfo, Scopus and Web of Science databases yielded 251 non-duplicate records published since 2000. Ten records examining the association between Clinical Dementia Rating (CDR) scores and apraxia in AD were included in the review. RESULTS: Dementia severity was related to apraxia in AD, and the prevalence and severity of apraxia increased as dementia progressed. Constructional, ideomotor (imitation of meaningless gestures), orofacial, speech, gait, and total praxis, including constructional, ideomotor, and ideational praxis, tasks differentiated dementia severity in AD. In the atypical variants of AD apraxia occurred frequently but because of the small number of participants, no statistical analyses were available. CONCLUSIONS: The results highlight the need for extensive assessment of AD severity, and praxis assessment throughout the disease course. Apraxia affects the independent functioning and communication of the patient, tool use, and the ability to perform activities of daily living. Apraxia occurs frequently in AD and other neurodegenerative diseases, and apraxia assessment has shown to differentiate AD from other neurodegenerative diseases, particularly frontotemporal dementia. Thus, apraxia assessment serves in recognizing the atypical variants of AD as well.

Low Expression of miR-18a as a Characteristic of Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) occurs in both adults and children but the response to chemotherapy and survival is significantly worse in the adults. We aimed to study whether the expression of immune system-associated miRNAs would differ between adult and pediatric patients with ALL at the time of diagnosis. MATERIALS AND METHODS: Inflammation-associated miRNA analysis was performed in 19 adults and 79 pediatric patients with ALL and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339. MiRNAs were first analyzed by miRNA microarray and thereafter validated by qRT-PCR. Sufficient RNA for qRT-PCR was available for 42 pediatric and 19 adult patients. RESULTS: Of the studied miRNAs, only miR-18a differed significantly in microarray analysis between adult and pediatric ALL, being lower in children (FC, -3.74; P, 0.0037). Results were confirmed by qRT-PCR (down-regulated in pediatric patients, P 0.003161). The other members of the miR-17-92 cluster did not differ significantly. CONCLUSIONS: Pediatric and adult patients with ALL have remarkably similar patterns of immune-cell-associated miRNAs in their bone marrow at diagnosis. However, the low expression of miR-18a in pediatric ALL is interesting and demands further study.

Imatinib and pegylated IFN-α2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response.

OBJECTIVES: Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-α2b) and imatinib may increase the rate of successful discontinuation. METHODS: In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg-IFN-α2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed. RESULTS: In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR(4.0) 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg-IFN-α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR(4.0) at 58 months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells. CONCLUSIONS: A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.

Killer-cell immunoglobulin-like receptor gene profile predicts good molecular response to dasatinib therapy in chronic myeloid leukemia.

Tyrosine kinase inhibitors have greatly improved the prognosis of chronic myeloid leukemia (CML). In addition to direct kinase inhibition, their effects can also be mediated through immune modulation, such as expansion of cytotoxic T and natural-killer cells observed during dasatinib therapy. As natural-killer cell and partially CD8(+) T-cell function are regulated by killer immunoglobulin-like receptors (KIRs), we studied whether the KIR gene profile is associated with clinical therapy response in dasatinib-treated CML patients (n = 191). In first-line patients, the absence of the inhibitory KIR2DL5A (p = 0.0489), 2DL5B (p = 0.030), and 2DL5all (p = 0.0272) genes were associated with improved molecular response at the 12-month time point. In addition, the same trend was seen with two activating KIR genes, 2DS1 (p = 0.061) and 2DS2 (p = 0.071). Furthermore, when patients were clustered into two groups by their KIR gene profile, the BCR-ABL1 transcript levels differed significantly between the groups (p = 0.047), showing that patients who lacked several KIR genes had better response. The comparison of first-line and second-line patients did not show any significant differences in either KIR or human leukocyte antigen genotypes. Our results show that immunogenetic factors, such as the KIR gene profile, can play a role in tyrosine kinase inhibitor therapy response. Additional studies are warranted to elucidate the functional significance of KIR genes associated with treatment outcomes.