Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer's Disease Treated with Anti-Amyloid Beta Therapy.

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aß) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aß in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aß therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.

Differentiating clinical groups using the serial color-word test (S-CWT).

The present study attempted to differentiate 11 diagnostic groups by means of the Serial Color-Word Test (S-CWT), using multivariate discriminant analysis. Two alternative scoring systems of the S-CWT were outlined. Asample of 514 individuals who had clinical diagnoses of various types and 397 controls who had no diagnostic findings comprised the sample. The first discriminant analysis failed to differentiate the groups adequately. The groups were consequently reduced to four (schizophrenia, bipolar disorders, temporo-mandibular joint pain dysfunction syndrome, and eating disturbances), which gave better reclassification findings for a clinical application of the test. This classification gave over 55% correct assignments. The final four groups had a statistically significant discrimination on the test, which remained stable also in a bootstrap procedure. Implications for treatment indications and outcomes as well as strategies for further studies using the S-CWT are discussed.

Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021.

Alzheimer's disease is a progressive, irreversible neurodegenerative disease impacting cognition, function, and behavior. Alzheimer's disease progresses along a continuum from preclinical disease, to mild cognitive and/or behavioral impairment and then Alzheimer's disease dementia. Recently, clinicians have been encouraged to diagnose Alzheimer's earlier, before patients have progressed to Alzheimer's disease dementia. The early and accurate detection of Alzheimer's disease-associated symptoms and underlying disease pathology by clinicians is fundamental for the screening, diagnosis, and subsequent management of Alzheimer's disease patients. It also enables patients and their caregivers to plan for the future and make appropriate lifestyle changes that could help maintain their quality of life for longer. Unfortunately, detecting early-stage Alzheimer's disease in clinical practice can be challenging and is hindered by several barriers including constraints on clinicians' time, difficulty accurately diagnosing Alzheimer's pathology, and that patients and healthcare providers often dismiss symptoms as part of the normal aging process. As the prevalence of this disease continues to grow, the current model for Alzheimer's disease diagnosis and patient management will need to evolve to integrate care across clinical disciplines and the disease continuum, beginning with primary care. This review summarizes the importance of establishing an early diagnosis of Alzheimer's disease, related practical 'how-to' guidance and considerations, and tools that can be used by healthcare providers throughout the diagnostic journey.

Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia.

Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3' enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80 percent; controls-68 percent). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2*2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A allele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-kB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3' IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected.

Early adverse experiences in schizophrenia and unipolar depression.

To study the prevalence of early adversities in schizophrenia and unipolar depression, 2 groups of consecutive adult-onset inpatients with DSM-IV diagnoses of schizophrenia (n = 173) and unipolar depression (n = 305) were compared with an unscreened control group of volunteers from the general population (n = 310), with respect to their association with 4 types of childhood abuse and with early parental adversities (discord, separation, death, psychiatric caseness). Compared with general population, most types of early adversities (except sexual abuse and parental death) were significantly associated with both clinical groups. Compared with depression, all early adversities with the same 2 exceptions were significantly associated with schizophrenia; both frequency of abuse and number of types of abuse increased the risk of schizophrenia in a dose-response pattern, suggesting causality. These findings stress the role of social developmental factors in the etiology of schizophrenia.

Personality differences between depressed melancholic and non-melancholic inpatients.

OBJECTIVE: The aim of the present study was to confirm that non-melancholic depression corresponds to a higher degree of personality dysfunction compared to melancholia. METHOD: A total of 188 inpatients, with a main DSM-IV diagnosis of major depressive disorder, were classified as melancholic and non-melancholic according to CORE system, DSM-IV, Research Diagnostic Criteria (RDC) Retarded Depression, and RDC Agitated Depression. Personality was assessed by means of the Temperament and Personality Questionnaire (T&P). Only patients at the nadir of their episode were included. RESULTS: Compared to non-melancholic depressives, patients with CORE melancholia scored lower on social avoidance and higher on effectiveness and cooperativeness; patients with RDC Retarded Depression scored lower on Anxious-Worrying and Cooperativeness; patients with RDC Agitated Depression scored lower on Social Avoidance, Rejection Sensitivity and Anxious-Worrying, and higher on Effectiveness; while patients with DSM-IV melancholia scored higher on Irritability and lower on Cooperativeness. Both CORE and RDC Agitated Depression were associated with higher scores of Perfectionism. CONCLUSIONS: The hypothesis of an association of melancholic depression with less marked personality dysfunction was confirmed for CORE melancholia and RDC Agitated Depression, and not supported for DSM-IV melancholia. Mixed evidence was obtained for RDC Retarded Depression. Personality of melancholic depressives seems to be characterized not only by less dysfunction but also by perfectionism, akin to the features of Tellenbach's typus melancholicus.

A comparative study of axis I antecedents before age 18 of unipolar depression, bipolar disorder and schizophrenia.

BACKGROUND: Despite a large scientific literature on early clinical precursors of schizophrenia, bipolar disorder and unipolar depression, few data are available on axis I disorders preceding the adult onset of these illnesses. SAMPLING AND METHODS: Disorders before the age of 18 years were retrospectively assessed with a structured interview in 3 groups of consecutive adult inpatients with DSM-IV diagnoses of schizophrenia (n = 197), major depressive disorder (n = 287) and bipolar disorder (n = 132). Only patients with adult onset of schizophrenia and of mania/hypomania were included. A sample of the general population served as control group (n = 300). RESULTS AND CONCLUSION: The clinical groups significantly outnumbered the control sample on the majority of early axis I diagnoses. Schizophrenia was significantly associated (1) with attention deficit hyperactivity disorder (ADHD), ADHD inattentive subtype, ADHD hyperactive subtype and primary nocturnal enuresis, compared to unipolar depression, and (2) with social phobia and ADHD inattentive subtype, compared to bipolar disorder. Oppositional defiant disorder was significantly associated with bipolar disorder, compared to the other clinical and control groups. The ADHD hyperactive subtype predicted the adult onset of bipolar disorder compared to unipolar depression. Externalizing disorders seem of special importance as regards the clinical pathways toward schizophrenia.

The defense mechanism test-separation theme in two anxiety disorders.

Two groups of 26 age- and sex-matched outpatients, with DSM-IV diagnoses of obsessive-compulsive disorder and panic disorder with agoraphobia, were compared on the Defense Mechanism Test-Separation Theme. A stimulus portraying a mother figure who is leaving a room where a baby lies alone on the floor was presented 22 times at increasing exposure durations in a single-view tachistoscope. Participants were asked to describe what they perceived at each step, according to the method of the Defense Mechanism Test. As predicted, reports of the mother seen as an inanimate object (phobic repression) were statistically significantly associated with agoraphobia, while reports of the mother entering the room or doing something other than leaving the baby (reaction formation) and reports of the baby as an angel (intellectualization) were associated with obsessive-compulsive disorder.

Signs of defense in obsessive-compulsive disorder: a validation study of the Defense Mechanism Test.

A group of 31 patients with Obsessive-Compulsive Disorder was compared with an age and sex-matched group of 31 nonclinical volunteers on the Defense Mechanism Test, a tachistoscopic paradigm which confronts the subject with anxiety-arousing stimuli at increasing durations from subliminal levels until complete recognition. It was hypothesized that distortions of the stimuli coded as Isolation or Reaction Formation would be more frequent in the obsessive-compulsive sample. Reaction Formation and one variant of Isolation (Barrier Isolation) were significantly associated with the obsessive-compulsive diagnosis.

Patterns of adaptation in obsessive-compulsive disorder: multivariate indicators of greater variability and linear change compared to controls.

Patterns of adaptation to conflict in persons with Obsessive-Compulsive Disorder were assessed with the Serial Color-Word Test. Obsessive-Compulsive patients (n=50) were compared with an age- and sex-matched group of nonclinical volunteers. Measures of linear and nonlinear change in reading times during each of the five consecutive trials of the test were compared between groups by means of a multivariate model with doubly repeated measures. The multivariate analysis yielded a significant between-groups result (Wilks Lambda = .76, p < .001), mainly supported by higher values of nonlinear change in the Obsessive-Compulsive group. Thus, the discriminative ability of the Serial Color-Word Test was confirmed when individual differences were removed from the error term.

Patterns of adaptation to conflict and schizoid personality scale scores.

A previous investigation gave no evidence of a significant relationship of patterns of adaptation to conflict, as measured with the Serial Color-Word Test, with the Schizoid Personality Scale of the Coolidge Axis II Inventory. As a new scoring algorithm has subsequently been proposed for the latter scale, a replication was done with the modified schizoid scale. A group of 75 consecutive nonpsychotic women outpatients was given the Serial Color-Word Test and Coolidge's inventory. Both multiple and logistic regressions selected two significant predictors of schizoid personality, corresponding to high values of linear change in reading times during Trials 3 and 5 of the Serial Color-Word Test, i.e., to an increasingly rigid and inflexible style of the adaptive process. A multivariate analysis of variance yielded an effect size of .22 (partial eta2).

The extension of resin tags in etched dentin: a misinterpretation?

AIM: The morphological characteristics of the filament structure, universally recognized as resin tags, in samples prepared using a new SEM methodology, are analyzed . METHODS: Ten non-carious, human third molars were cut transversally to obtain 10 dentinal surfaces. They were filled using an adhesive restorative technique. Subsequently, the samples were cut lengthwise to be SEM observed, and then randomly divided into 6 main groups according to the preparation modality of the section surface: Group A: EDTA; Group B: H(3)PO(4); Group C1: H(3)PO(4)+NaOCl; Group C2 H(3)PO(4)+NaOCl+H(2)O(2); Group D1: HCl+NaOCl; Group D2: HCl+NaOCl+H(2)O(2). RESULTS: The resin tags which originate from resin penetration and polymerization within the dentinal tubules are small conic-trunk shaped plugs that are a few microns long. The thinner extension of the resin tags is probably due to the persistence of the lamina limitans. CONCLUSIONS: A new method of specimen preparation for SEM visualization is proposed in order to effectively evaluate the penetration capacity of the adhesive in the dentinal substratum. In addition to the use of strong acids and bases, an agent capable of degrading the glycosaminoglycans was employed to completely remove the dentinal organic component.

Styles of adaptation in autoimmune thyroiditis and bipolar disorder: a pilot study.

BACKGROUND: A growing body of evidence suggests that styles of adaptation, assessed with the Serial Color-Word Test (S-CWT, a 5-trials Stroop task), are able to differentiate several mental and psychosomatic disorders. Recent findings have confirmed a very high rate of cases of autoimmune thyroiditis (so called Hashimoto disease) among bipolar patients, suggesting an etio-pathogenetic relatedness between the two ailments. Based on the latter relatedness, it was hypothesized that the same styles of adaptation, which are known to differentiate bipolar and control subjects are also characteristic of patients with autoimmune thyroiditis. METHODS: Three groups (autoimmune thyroiditis, fully remitted bipolar I, and nonclinical) of 40 women, matched on age and schooling, were administered the S-CWT. The following variables were considered: (a) early discontinuity (i.e. the summed nonlinear change of the first three trials), (b) late discontinuity (i.e. the summed nonlinear change of the last two trials), (c) across-trials discontinuity (i.e. the nonlinear change of the five measures of nonlinear change). RESULTS: The thyroiditis group had (1) higher values of early discontinuity (P=0.006) and of late discontinuity (P=0.004) compared with nonclinical controls, (2) lower values of early discontinuity (P=0.005) and of across-trials discontinuity (P=0.008) compared with the bipolar group. LIMITATIONS: The study did not include men patients and lacked a quantification of affective symptoms among clinical and nonclinical participants. CONCLUSION: A discontinuous style of adaptation is more marked among remitted bipolar than among thyroiditis patients, and more marked among the latter ones than among nonclinical controls, thus delineating a sort of adaptive continuum.

A controlled study on oral propafenone versus digoxin plus quinidine in converting recent onset atrial fibrillation to sinus rhythm.

UNLABELLED: Eighty-seven patients with recent onset atrial fibrillation (< or = 8 days) without clinical signs of heart failure were randomly allocated to one of the following treatments: (i) oral propafenone (600 mg as a loading dose followed after 8 h by 300 mg t.i.d.); (ii) intravenous digoxin as acute scheme (up to 1.125 mg/24 h) followed after 6 h by hydroquinidine chlorhydrate (total dose, 1350 mg); or (iii) placebo. The patients were submitted to Holter monitoring for 48 h. RESULTS: propafenone achieved higher successful conversion rates at 6, 12 and 24 h compared either with placebo (62% vs. 17%, 83% vs. 34%; 86% vs. 55%; P < 0.01, respectively) or with digoxin at 6 h (62% vs. 38%; P < 0.05) and digoxin plus quinidine at 12 h (83% vs. 48%; P < 0.05). At 48 h, a placebo conversion rate of 76% was observed with consequent lack of any significant difference with the active treatments. Mean conversion times within 48 h were 267 +/- 238 min for propafenone, 648 +/- 631 min for digoxin plus quinidine (P < 0.01 vs. propafenone) and 893 +/- 622 min for placebo (P < 0.001 vs. propafenone). Propafenone and digoxin plasma levels were within the therapeutic range. Asymptomatic phases of atrial flutter with > or = 2:1 atrio-ventricular conduction ratio were observed during Holter monitoring, before conversion to sinus rhythm, in four patients treated with propafenone, in one patient taking digoxin plus quinidine and in four patients with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide evaluation of ventricular function at rest and during exercise in double inlet ventricle.

We studied ventricular volumes and ejection fraction by radionuclide angiography (equilibrium technique) in 15 patients (aged 3-48 years) with double inlet ventricle not yet submitted to corrective surgery. The end-diastolic volume (measured in nine cases) ranged from 108 to 219 ml/m2 (156 +/- 32), being lower than the normal theoretical value (right plus left ventricle) in six cases. Ejection fraction ranged from 30 to 77% (56.4 +/- 13). The value was significantly higher in the subgroup of 10 patients with a dominant left ventricle as compared to the five cases with dominant right or indeterminate ventricular morphology (63.2 +/- 8.3 versus 42.8 +/- 9, P less than 0.01). In seven of the 15 patients, measurements were obtained both at rest and during dynamic exercise in the semi-upright position. The end-diastolic and end-systolic volumes, stroke volume, ejection fraction underwent a slight non-significant reduction (from 158 +/- 29 to 147 +/- 24 ml/m2, from 58 +/- 16 to 56 +/- 24 ml/m2, from 100 +/- 27 to 90 +/- 24 ml/m2, from 64% +/- 9 to 61% +/- 13). During exercise, ventricular volumes mostly behaved as follows: slight reduction of end-systolic volume, decrease of end-diastolic volume, no increase (no change or decrease) of ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral Acanthosis nigricans as a marker of internal malignancy. A case report.

BACKGROUND: Acanthosis nigricans (AN) is a rare mucocutaneous condition that can involve the oral tissues. There are 2 clinical forms of AN: benign and malignant. Benign AN is related to systemic diseases such as diabetes and obesity or can be induced by drugs such as systemic corticosteroids, nicotinic acid, estrogens, insulin, and fusidic acid. Malignant AN appears in association with tumors such as lung, ovarian, breast, and gastric carcinoma. METHODS: A rare case of malignant AN that initially manifested in the oral cavity of a 73-year-old patient is reported. RESULTS: A bladder and lung carcinoma were detected following the diagnosis of AN. CONCLUSIONS: The diagnostic importance of oral AN is emphasized because, in our patient, its recognition led to the detection of 2 occult malignant tumors.

Separation-individuation, aggression and alexithymia in psoriasis.

A psychosomatic study of psoriasis was conducted in order to: 1) assess the level of extra- and intra-aggression (cf. the conflicting results in Matussek et al. (1) and Lyketsos et al. (2)); 2) point out the presence of alexithymia, i.e. impoverished fantasy life and inability to describe the emotions (cf. some negative results in Fava et al. (3)); and 3) explore the interactional variables, connected with the pathology of the separation-individuation process.

Adenoid cystic carcinoma of sweat glands: report of two cases.

Two cases of primary cutaneous adenoid cystic carcinoma (ACC) of sweat gland origin are reported. The patients were a 83-year-old man and a 40-year-old woman. Histologically, the neoplasms showed the classic appearance of ACC. CEA, actin and S-100 protein were immunocytochemically demonstrated to be contained in some neoplastic cells. The literature on sweat gland ACC is reviewed and the clinicopathologic profile of this rare tumor considered.

Microgenetic styles of regulation among two nonpsychotic psychiatric groups.

The serial version of the Color-Word Test was employed to assess the regulative styles (or adaptive patterns) of two nonpsychotic psychiatric groups, one with Panic Disorder and Agoraphobia, the other without either of the latter two diagnoses. Agoraphobics (n = 30) were individually matched for sex, age, and education with nonagoraphobic patients and with nonclinical controls. Compared with normals, nonagoraphobic patients had fewer Stabilized (S) and more Cumulative-Dissociative (CD) Primary Types, fewer Cumulative (Cr) and more Dissociative (Dr) and Cumulative-Dissociative R-types (CDr), more Dissociative V-types (Dv). The agoraphobic sample showed styles more akin to those of normal persons than to the other psychiatric group with the exception of an elevated frequency of R-Dissociation (Vr type). Interestingly, very low scores on several secondary variables were more frequent in the clinical groups than in the nonclinical sample.

Styles of adaptation in panic disorder with and without agoraphobia.

Two groups of women with a main DSM-IV diagnosis of panic disorder, one with and one without agoraphobia (respectively, n = 26 and n = 14) were compared on several clinical variables. Forward logistic regressions were run for the presence of agoraphobia. Age of onset, duration of illness, presence of major depressions, and cluster classification on Axis II did not predict the criterion variable. Diagnosis and scores on avoidant personality disorder led, respectively, to 65% and 72.5% rates of correct classifications. Among panic symptoms, fear of going crazy and palpitations significantly predicted agoraphobia (75% of correct allocations). Three adaptive variables assessed by the Serial Color-Word Test (a serial version of the Stroop task) led to a 90% rate of correct classification. Agoraphobic patients were mainly characterized by an anxious or over-controlling style, which permitted a pseudo-objective mastery of the conflict situation. The findings seem to support the clinical relevance of the Serial Color-Word Test.