VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a "high-risk" patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD.

Active immunotherapy and alternative therapeutic modalities for Alzheimer's disease.

As knowledge of Alzheimer's disease (AD) progression improves, the field has recognized the need to diversify the pipeline, broaden strategies and approaches to therapies, as well as delivery mechanisms. A better understanding of the earliest biological processes of AD/dementia would help inform drug target selection. Currently there are a number of programs exploring these alternate avenues.

Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral metabolic rate.

We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10) characterized by an unremitting and severe course and the non-Kraepelinian subtype (n = 17) characterized by a remitting course and some periods of self-care. Patients were assessed with positron emission tomography (PET) with 18F-deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI).

Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients.

Background: Geriatric schizophrenic patients with a chronic course of institutionalization manifest cognitive and functional impairments that implicate decline at some time point after the onset of illness. The rate of change in cognitive and functional status in these patients has not yet been identified with a longitudinal study.

Methods: Three hundred and twenty-six schizophrenic patients entered a 30-month follow-up study with two separate assessments of the patients.

Postmortem studies in schizophrenia.

The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia.

AMPA receptor binding and subunit mRNA expression in prefrontal cortex and striatum of elderly schizophrenics.

The dopamine hypothesis of schizophrenia has recently evolved into a model of dysfunctional integration between cortical and subcortical dopaminergic activity. Anatomical data suggest that regional alterations in dopaminergic activity may be linked by means of the rich glutamatergic innervation of the striatum by corticostriatal projections, suggesting a potential role for glutamatergic dysfunction in schizophrenia. Although pharmacological data have implicated the NMDA subtype of glutamate receptor in this illness, disturbance in AMPA receptor expression could potentially lead to the NMDA receptor hypoactivity hypothesized in schizophrenia.

Ventricular enlargement in poor-outcome schizophrenia.

Background: A subset of patients with schizophrenia, defined on the basis of longitudinal deficits in self-care, may show a classic ("Kraepelinian") degenerative course. An independent validator of the phenomenologically defined Kraepelinian subtype might be provided by a structural indicator of possible brain degeneration: ventricular size as measured by computed tomography (CT).

Methods: To examine whether Kraepelinian patients would show a differential increase in ventricular size over time, two CT scans were conducted at intervals separated by > 4 years, an average of 5 years.

Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases.

Background: Clinical studies suggest that severe cognitive impairment is common among elderly patients with schizophrenia who reside in long-stay psychiatric institutions; however, previous autopsy-based neuropathologic investigations have provided conflicting results about the occurrence of Alzheimer disease (AD) in elderly patients with schizophrenia. We report the results of a comprehensive neuropathologic study performed to identify AD and other dementing neurodegenerative diseases in elderly patients with schizophrenia.

Methods: A neuropathologic examination was performed on 100 consecutive autopsy brain specimens of patients aged 52 to 101 years (mean, 76.

Verbal fluency deficits in geriatric and nongeriatric chronic schizophrenic patients.

This study examined age-related differences and correlates of deficits on phonological and category fluency tasks performed by schizophrenic patients. Equal numbers (n = 41) of geriatric (age > 64) and nongeriatric chronically hospitalized schizophrenic patients were examined with tests of phonological and category fluency, verbal learning and delayed recall, confrontation naming, and reading, as well as overall estimates of cognitive impairment. Both types of fluency tests were performed very poorly by both groups.

Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia.

Background: The identification of novel subtypes of the dopamine receptors has renewed interest in the involvement of dopaminergic mechanisms in schizophrenia. We determined the expression of transcripts encoding the dopamine receptors in the brains of schizophrenic patients.

Methods: The levels of the messenger RNA molecules encoding the 5 dopamine receptors were quantified in postmortem brain samples from 16 schizophrenic patients and 9 control subjects.

Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia.

Background: Cytoarchitectural and neurochemical studies demonstrate disorganization in the cerebral cortex in schizophrenia, which perhaps underlies the severe behavioral disturbances of the disease. This neuronal disarray should be accompanied by synaptic abnormalities. As such, presynaptic proteins have proved valuable indexes of synaptic density and their concentrations have correlated markedly with synaptic loss.

Symptom severity and cognitive impairment in chronically hospitalised geriatric patients with affective disorders.

Background: Affective disorders typically have a better outcome than schizophrenia, although recent evidence suggests that some patients with affective disorder have a relatively poor outcome, with cognitive impairments and persistent symptomatology.

Method: Fifty chronically hospitalised geriatric patients with mood disorders (major depression or bipolar disorder) were compared on the clinical symptoms and aspects of cognitive impairment with 308 geriatric schizophrenic patients who were hospitalised at the same institution. The two samples did not differ in current age or in premorbid education level, but the affective patients had a later age of onset and more females in the sample.

Age-related differences in formal thought disorder in chronically hospitalized schizophrenic patients: a cross-sectional study across nine decades.

Objective: This study used a cross-sectional design to examine the frequency of occurrence and severity of 10 different signs of thought disorder in schizophrenic patients across the lifespan.

Method: Schizophrenic patients, who ranged in age from 19 to 96 years (N = 392), were examined with the Scale for Assessment of Thought, Language, and Communication. The cognitive functioning of the geriatric patients (patients over the age of 64, N = 120) was also assessed.

Social-Adaptive Functioning Evaluation (SAFE): a rating scale for geriatric psychiatric patients.

Geriatric chronic psychiatric inpatients often remain in a chronic psychiatric hospital because of serious deficits in adaptive life functions. Because the additional complications and adaptive changes associated with aging have not been considered in previous scales, the Social-Adaptive Functioning Evaluation (SAFE) was developed. The items in the scale measure social-interpersonal, instrumental, and life skills functioning and are designed to be rated by observation, caregiver contact, and interaction with the subject if possible.

Cognitive impairment and negative symptoms in geriatric chronic schizophrenic patients: a follow-up study.

Cognitive impairment is increasingly recognized as an important aspect of schizophrenia. Since cognitive impairment has many features in common with the negative symptoms of the illness, it is possible that some of the characteristics attributed to negative symptoms are due to an association with cognitive impairments. In order to test this hypothesis, 174 chronically hospitalized geriatric schizophrenic patients were examined twice at a 1-year follow-up with ratings of the severity of their symptoms (using the Positive and Negative Syndrome Scale: PANSS) and assessments of cognitive functions with the Mini-Mental State Examination and a brief neuropsychological battery aimed at the typical impairments seen in dementia.

Cognitive functioning in late-life schizophrenia: a comparison of elderly schizophrenic patients and patients with Alzheimer's disease.

Objective: Previous studies have suggested that geriatric inpatients with chronic schizophrenia manifest profound cognitive impairments. This study investigated how these cognitive impairments resemble those seen in degenerative dementing conditions.

Method: The neuropsychological battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), widely used to characterize the cognitive deficits of patients with Alzheimer's disease, was used to compare patterns of cognitive impairment in 66 triads of subjects consisting of one elderly patient with Alzheimer's disease, one elderly, institutionalized patient with chronic schizophrenia, and one elderly, cognitively normal comparison subject who were matched on age, gender, and education.

Age disorientation in chronically hospitalized patients with mood disorders.

Age disorientation was studied in 45 geriatric patients with chronic mood disorders. In a yearly assessment of cognitive functions, subjects were questioned about their age, year of birth, and the current year. Patients who misstated their age by > or = 5 years were considered age disoriented.

Symptom stability in geriatric chronic schizophrenic inpatients: a one-year follow-up study.

The results of previous studies of symptom stability in schizophrenia suggest that negative symptoms manifest traitlike characteristics while positive symptoms fluctuate over time. Various prospective studies of chronic schizophrenic patients have found consistent results, regardless of the follow-up period, yet there is little research addressing symptomatology in geriatric schizophrenic patients. Since these patients have a very poor outcome and more severe negative symptoms, their symptoms might differ from younger patients.

Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex.

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group.

Cognitive functioning in chronically hospitalized schizophrenic patients: age-related changes and age disorientation as a predictor of impairment.

Although schizophrenic patients manifest cognitive impairments, there is considerable variability across patients in the severity of this impairment. Very chronic patients with a poor outcome, particularly geriatric patients, manifest the most severe impairments, which have often been characterized as resembling dementia. This study examined age-related changes in cognitive functioning in a sample of schizophrenic patients (n = 393) ranging from 25 to 95 years of age, with a specific focus on identifying aspects of performance that were impaired in the youngest patients and preserved in the oldest patients.

The longitudinal stability of cognitive impairment in schizophrenia. Mini-mental state scores at one- and two-year follow-ups in geriatric in-patients.

Background: Severe cognitive impairment affects many patients with schizophrenia, especially geriatric in-patients. Little is known about the course of this impairment, however.

Method: Two hundred and twenty-four geriatric schizophrenic in-patients were examined for changes in cognitive functioning over a one-year follow-up period, and 45 of them were assessed over a two-year period.

Severity of symptoms in chronically institutionalized geriatric schizophrenic patients.

Objective: The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence.

Method: The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years.

Results: In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed.