Clinical predictors of Alzheimer's disease-like brain atrophy in individuals with memory complaints.

OBJECTIVES: The definition and assessment methods for subjective cognitive decline (SCD) vary among studies. We aimed to investigate which features or assessment methods of SCD best predict Alzheimer's disease (AD)-related structural atrophy patterns. METHODS: We assessed 104 individuals aged 55+ with memory complaints but normal cognitive screening. Our research questions were as follows: To improve the prediction of AD related morphological changes, (1) Would the use of a standardized cognitive screening scale be beneficial? (2) Is conducting a thorough neuropsychological evaluation necessary instead of relying solely on cognitive screening tests? (3) Should we apply SCD-plus research criteria, and if so, which criterion would be the most effective? (4) Is it necessary to consider medical and psychiatric comorbidities, vitamin deficiencies, vascular burden on MRI, and family history? We utilized Freesurfer to analyze cortical thickness and regional brain volume meta-scores linked to AD or predicting its development. We employed multiple linear regression models for each variable, with morphology as the dependent variable. RESULTS: AD-like morphology was associated with subjective complaints in males, individuals with advanced age, and higher education. Later age of onset for complaints, complaints specifically related to memory, excessive deep white matter vascular lesions, and using medications that have negative implications for cognitive health (according to the Beers criteria) were predictive of AD-related morphology. The subjective cognitive memory questionnaire scores were found to be a better predictor of reduced volumes than a single-question assessment. It is important to note that not all SCD-plus criteria were evaluated in this study, particularly the APOE genotype, amyloid, and tau status, due to resource limitations. CONCLUSIONS: The detection of AD-related structural changes is impacted by demographics and assessment methods. Standardizing SCD assessment methods can enhance predictive accuracy.

Effects of Clozapine on Cortical Inhibition: A Transcranial Magnetic Stimulation Follow-up Study.

BACKGROUND: Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. METHODS: Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. RESULTS: Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. CONCLUSIONS: This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.

Combination With Long-Acting Injectable Antipsychotics and Utilization of Nonstandard Formulations as Compliance Enhancing Methods for Clozapine Users: A Systematic Review and A Case Series.

BACKGROUND: Combining clozapine with a long-acting injectable antipsychotic (LAI) or using different, nonstandard formulations of the compound may improve treatment outcomes. We aimed to investigate the utility of the clozapine-LAI combination and different formulations of clozapine for compliance problems of clozapine treatment, and to describe a case series on the combined treatment. PROCEDURES: We conducted a PubMed search with no date restriction. The number and length of hospitalizations, the results of clinical scales, and adverse events were recorded. We also present a case series of 18 patients using the clozapine-LAI combination. Data were collected from the medical charts and electronic records. RESULTS: We extracted 9 records describing the use of the clozapine-LAI combination. The case reports and mirror-image studies showed a significant reduction in the number of hospitalizations, length of hospital stays, and number of visits to the emergency department on the combined treatment with no serious adverse events. We included 11 articles for clozapine formulations. The case reports and retrospective data suggested that short-acting intramuscular clozapine was often well tolerated and resulted in an increased acceptance of oral clozapine in the acute phase of illness. In our case series, illness severity and the number of hospitalization per year significantly decreased after the combined treatment, besides a significant improvement in the functioning scores. Hyperprolactinemia and extrapyramidal side effects were reported due to concomitant LAIs. CONCLUSIONS: Despite the encouraging evidence, the present data are preliminary and mostly based on retrospective studies, and oral-dissolving tablets or oral liquid formulations of clozapine have insufficient evidence for clinical practice. Well-designed, controlled, follow-up studies are needed for both clozapine-LAI combination and different formulations of clozapine.