Next Article in Journal
Downstream Imaging Studies Do Not Significantly Improve Outcome in Most Patients with Chest Pain Who Did Not Reach Their Target Heart Rate on a Stress ECHO Study
Previous Article in Journal
Leveraging the Academic Artificial Intelligence Silecosystem to Advance the Community Oncology Enterprise
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Vascular Schizophrenia-like Psychosis in Older Adults

1
Complex Unit of Geriatrics, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy
2
Clinical Psychology Service, Health Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy
3
Laboratory of Gerontology and Geriatrics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2023, 12(14), 4831; https://doi.org/10.3390/jcm12144831
Submission received: 6 June 2023 / Revised: 5 July 2023 / Accepted: 20 July 2023 / Published: 22 July 2023
(This article belongs to the Section Mental Health)

Abstract

:
Background: The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. Methods: In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. Results: Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). Conclusions: The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

1. Introduction

Schizophrenia (SZ) is a severe psychopathological syndrome characterized by delusions, hallucinations, and impaired skills and social relationships [1,2]. Usually, it first manifests in adolescence or early adulthood [3] but 20% of patients have their first onset after the age of 40 [4] and 1% of the older population present psychotic symptoms [5]. This is a frequent complication of cognitive impairment due to Alzheimer’s Disease or Vascular Dementia, especially in the more advanced stages of the diseases [6]. Otherwise, onset in older adults with normal cognitive functions is a rare condition but with a consequent worsening of functional autonomy and life expectancy [7]. For many years, there has been a growing interest in the relationship between behavioral disorders, aging, and vascular risk factors [8,9]. Since the first studies, these factors were linked to the presence of White Matter Hyperintensity (WMH) signals [10,11] and Brain Atrophy (BA) [12,13]. In particular, the early researchers began to investigate WMH and BA in subjects with schizophrenia [14,15] and showed that subjects with Late-Onset Schizophrenia have a greater prevalence rate of WMH [16]. This condition has been proven to be closely related to atherosclerosis [17], thromboembolism [18], and chronic cerebral hypoperfusion [19]. Indeed, Cardiovascular Disease (CVD) is much more prevalent in SZ than in the general population, and recent studies on functional genomics indicate that schizophrenia may be an adult vascular–ischemic disorder [20,21,22]. Endothelial Dysfunction (ED) has been described as a risk factor and mechanism in itself of the development of CVD [23,24]. In particular, the chronic inflammatory response [25] and the increased vasoconstriction [26] and oxidative stress [27] have attracted great interest in the relationship between CVD and SZ [28]. Regarding the diagnostic classification of patients, in relation to this problem, Geriatric Psychiatrists have published a review of the Conference of the International Late-Onset Schizophrenia Group. The authors concluded that Late-Onset Schizophrenia (LOS) begins after the age of 40 and bears a reasonable resemblance to early-onset schizophrenia (EOS), whereas Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) begins after the age of 60 and was best classified as having a schizophrenia-like psychosis on the basis of a convergence of clinical, epidemiological, neuroimaging, and neuropsychological data, although there was no consensus on the age limits for this distinction [29]. However, regarding the phenotypic characterization and clinical validity of LOP and VLOSLP, the discussion remains ongoing [30]. Indeed, some critical differences exist in their clinical presentation as compared with EOS. The results of various studies reported more positive symptoms in VLOSLP, a female preponderance, lower genetic risk, and higher rates of more-severe paranoid symptoms and persecutory delusions [31,32,33,34,35]. DSM-5 states that “late-onset cases can meet the diagnostic criteria for schizophrenia but it is not yet clear whether this is the same condition as schizophrenia diagnosed prior to mid-life” [36]. Discussion is needed on more than simply the cut-off for age of onset and clinical features. To date, it has not been clearly established whether it is a neurodegenerative pathology or a consequence of vascular damage. Investigating the neurobiology of VLOSLP is therefore the topic of our study. The aims of our study are
-
to analyze the prevalence and severity of vascular risk factors in a population of older patients referred to our clinic due to the onset of VLOSLP;
-
to create a specific phenotype based on pathophysiological insight rather than age of onset.

2. Materials and Methods

2.1. Study Sample

From January 2015 to December 2022, we screened older subjects who had consecutively attended the Cognitive Impairment Evaluation Unit of the Complex Unit of Geriatrics of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) “Casa Sollievo della Sofferenza” for possible study enrollment. We obtained written informed consent for research from each patient, or from relatives or a legal guardian.
All subjects were Caucasian, not including people of Jewish, Eastern European, or North African descent, with most individuals having Southern Italian ancestry, living in Southern Italy for at least three generations.
Inclusion criteria were (1) age ≥ 65 years; (2) diagnosis of Late-Onset Schizophrenia and Very-Late-Onset Schizophrenia-Like Psychosis according to International Late-Onset Schizophrenia Group (LOSG) criteria [29]; (3) absence of dementia; (4) presence of white matter hyperintensity based on computed tomography (CT scan); (5) treatment with acetylsalicylic acid already in progress; (6) ability to provide informed consent or availability of a relative or a legal guardian in the case of patients with severe cognitive impairment. Exclusion criteria were (1) presence of serious comorbidity, tumors, other diseases, or physiological status (ascertained blood infections, disorders of the thyroid, kidneys, or liver); (2) head trauma.

2.2. Study Design

The present study was conducted according to the Declaration of Helsinki, the Guidelines for Good Clinical Practice and the guidelines for Strengthening the Reporting of Observational Studies in Epidemiology, and it was approved by the local ethics committee for human experimentation (Prot. N. 3877/DS). This study was a longitudinal study, in which the assignment of an intervention to the participants, its effect assessment, and health-related biomedical or behavioral outcomes were not considered.

2.3. Cognitive, Neuropsychiatric, and Functional Assessment

In all patients, cognitive status was defined with the Mini-Mental State Examination (MMSE) [37], after a brief interview with the caregiver.
The neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI) [38], which consisted of 12 neuropsychiatric domains: delusions, hallucinations, depression, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, aberrant motor activity, sleep disturbance, and eating disorder.
In all patients, functional status was assessed by activities of daily living (ADL) [39] and instrumental activities of daily living (IADL) [40] scales.

2.4. Genotyping

Genotyping was conducted on blood samples. Apolipoprotein E (ApoE) alleles (corresponding to allele combinations at single nucleotide polymorphism (SNP) +3937/rs429358 and SNP + 4075/rs7412) were genotyped using the ABI 7900 Taqman (Applied Biosystems, Foster City, CA, USA) system. The two ApoE single nucleotide polymorphisms exist at amino acids 112 and 158, which were targeted by the Taqman probes. The individual genotypes at the two sites were then combined to create a single standard ApoE genotype.

2.5. Value Quantification of Biochemical Concentrations

The blood samples (3–5 mL of blood) were collected intravenously from an upper limb of each patient in the morning. Then, blood samples were stored in Vacutainer tubes containing citrate; within not more than 30 min, the samples were transferred to the department of biochemistry and analyzed in a full autoanalyzer.
The blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured in all patients.

2.6. Vascular Risk Factor Assessment

Through a semi-structured interview, medical history and milestones from the patient’s life were assessed as shown below: (1) lifetime tobacco use, (2) alcohol consumption, (3) psychoactive substance use and abuse, (4) history of vascular disease (hypertension, hyperlipidemia, diabetes mellitus, stroke, myocardial infarction, atrial fibrillation, and heart failure), and (5) anti-smooth muscle antibody (ASMA).
Following the guidelines for the diagnosis and management of hypertension in adults, hypertension was defined as systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or as currently receiving antihypertensive treatment [41].
Hyperlipidemia was defined according to the guidelines for management of dyslipidemia and prevention of cardiovascular disease [42]. All recruited patients with hyperlipidemia were in treatment with statins.
Diabetes mellitus was defined according to the Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm [43].
At the time of the medical visit, all patients were in treatment with acetylsalicylic acid; the patients with atrial fibrillation were in oral anticoagulant therapy.
All patients had performed a neuroimaging examination (CT scan) in order to highlight the presence of white matter hyperintensity. The focal cortical–subcortical outcomes were reported in patients with previous stroke.

2.7. Statistical Analyses

For dichotomous variables, hypotheses regarding differences between the groups were tested using chi-square test. This analysis was made using the 2-Way Contingency Table Analysis. For continuous variables, normal distribution was verified by the Shapiro–Wilk normality test and the one-sample Kolmogorov–Smirnov test. For normally distributed variables, hypotheses regarding differences among the groups were compared by means of Welch’s two-sample t-test or analysis of variance (ANOVA) under a general linear model. For non-normally distributed variables, hypotheses regarding differences among the groups were compared by means of the Wilcoxon rank sum test with continuity correction or by means of the Kruskal–Wallis rank sum test. Risks (adjusted by cognitive impairment presence/absence and severity) are reported as odds ratios (OR) along with their 95% confidence interval (CI). All the statistical analyses were made with the R Ver. 2.8.1 statistical software package [The R Project for Statistical Computing; available at URL http://www.r-project.org/ (accessed on 14 February 2023)]. Tests in which the p value was smaller than the type I error rate α = 0.05 were declared significant.

3. Results

During the enrollment period, 181 older patients were screened for inclusion in the study. Of these, 12 patients were excluded because they were younger than 60 years, 58 had a diagnosis of dementia, 6 had not run a CT scan, and 2 had an incomplete examination. Thus, the final population included 103 patients, comprising 39 men (37.86%) and 64 women (62.14%) with a mean age of 80.32 ± 7.65 years and a range from 65 to 95 years.

3.1. Demographic, Cognitive, Functional, Neuropsychiatric, and Clinical Characteristics

As shown in Table 1, dividing patients by gender, there was only a significant difference in NPI-Apathy: females were more apathetic than males (p = 0.040).
As shown in Table 2, dividing patients by gender, males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), than females; in terms of vascular risks, males used more tobacco (p = 0.046) and alcohol (p = 0.024) than females.

3.2. Vascular Risk Frequency

As the data in Table 3 show, we analyzed separately the frequency of vascular risk factors in patients < 80 years compared to patients ≥ 80 years, looking for differences according to age in the distribution of risk factors. We only found differences in the frequency of vascular risk factors comparing these two age strata for frequency of MI among men (p = 0.027).

3.3. Current Use of Antipsychotic and Antidepressant Drugs

Regarding psychiatric and clinical treatment (Table 4), 102 patients were treated for psychosis (75 with affective psychosis and 27 with no-affective psychosis), and 59.16% of them were using atypical antipsychotics (AA). The most commonly used drugs were serotonin selective reuptake inhibitor (SSRI) drugs (26 (26.52%) patients, 5 with no-affective psychosis) and typical antipsychotic (TA) drugs (17 (17.51%) patients, 8 with no-affective psychosis).

4. Discussion

In this study, we explored the neuropsychiatric profile of older people with psychotic symptoms arising in a state of normal cognitive function, paying close attention to vascular risk factors. We studied our patients, first of all, divided by gender and noting that most are female as in previous studies [44,45,46]. In our results, there are not only more females, but there is a greater degree of severity of psycho-behavioral symptoms as noted in the total NPI score that is higher than in males. Particularly in females, hallucinations, anxiety, and depressive symptoms are more severe. Males, on the other hand, express symptoms more frequently characterized by irritability and aggressiveness. To characterize the symptoms and investigate their onset and course, for each patient, the interview with the family was fundamental. All patients were described as having normal cognitive functions and complete independence in activities of daily living until the onset of psychiatric symptoms, after which they came to the attention of our clinic. Screening of cognitive functions, performed with the MMSE, shows a score below normal. This data must be considered in relation to the poor collaboration of all patients and the opposition shown towards the neuropsychometric tests that we attempted to perform. Finally, there were no differences between males and females regarding laboratory analyses performed to analyze blood count, glycolipid profile, liver and kidney function, folic acid, and vitamin B12.

4.1. Homocisteine and ApoE Gene

We analyzed homocysteine levels and the presence of the ɜ4 allele of the ApoE gene [47,48] considered as a link between vascular risk factors and brain damage. Homocysteine showed a higher concentration in the male population and the ɜ4 allele of the ApoE gene was more present in the female population. To the best of our knowledge, our work provides more information about the neuropsychiatric profile of onset of psychotic symptoms at an older age than other studies [34,35,49,50,51,52,53,54,55,56].

4.2. Endothelial Dysfunction

In addition, we focused on the prevalence of vascular risk factors and previous acute cardiac and cerebral vascular events. We also considered previous Acute Myocardial Infarctions (AMI) as an expression of systemic ED [53], which many studies associate with schizophrenia [57,58,59]. As mentioned, after analyzing the neuropsychiatric profile of our patients and dividing them into subgroups considering gender differences and age of onset < 80 and ≥80, our interest turned to the study of the causes. To deepen our understanding, we started from the anamnesis, focusing in particular on vascular risk factors, which became the subject of this study. Vascular risk factors we mean chronic systemic diseases, which cause ED, increase the likelihood of cardiac and cerebral vasculopathy, and put the patient at increased risk of Acute Vascular Events (AVE) [60]. The main piece of data to report is the prevalence of previous AVE, which in our population is 27.2%. Specifically, 14.6% reported a previous cerebral Ischemic Stroke (IS) with functional recovery, and 12.6% reported a previous AMI. Analyzing data, by gender and age, we found that in the male population over 80 years of age, the prevalence of previous AVE is 47.6%. In particular, previous IS is 23.8% and previous AMI is 23.8%. In the female population aged over 80, on the other hand, the prevalence of AVE is 29.4%. Specifically, previous IS is 11.8% and previous AMI is 17.6%. Moreover, the most evident piece of data is the constant comorbidity present in our patients. The pathologies most frequently known many years before the onset of psychotic symptoms are arterial hypertension, atrial fibrillation, heart failure, type 2 diabetes mellitus, and dyslipidemia under treatment. With our results, it is possible to hypothesize the predominantly vascular genesis of schizophrenia with onset after 80 years. ED could be the neurobiological substrate that predisposes patients to the onset of psycho-behavioral disorders, as shown by studies for which its markers are associated with significant changes in regional Cerebral Blood Flow (rCBF) [61]. In this regard, recent evidence suggests that apathy, depression, fatigue, and delirium are associated with rCBF changes, in particular hypoperfusion in the bilateral temporal lobes [62].

4.3. Neurovascular Unit Dysfunction

Finally, regarding the role of ED in neurobiology of schizophrenia, we share the recent theory of Neurovascular Unit (NU) dysfunction [63]. NU consists of the brain’s microvessels, pericytes, glial cells (astroglia, microglia, oligodendroglia), and neurons. It is the structure that arises from the interaction between glia, neurons, and the cerebral microvascular endothelium [64,65,66]. There are many clinical and experimental data that have studied the link from neuroinflammation, oxidative stress, and genetic factors to clinical and pathological findings suggestive of NU dysfunction in schizophrenia [67,68,69,70,71,72,73,74].

4.4. Vascular Schizophrenia-like Psychosis as Specific Phenotype

We therefore deem it necessary, with regard to “vascular depression”, which is known as a specific subtype distinct from nonvascular forms [75], and with regard to psychosis, to have a particular phenotype from which a different consequent prevention, follow-up, and treatment can be developed [76]. A more specific association between cerebral vasculopathy and psychotic disorders has been formalized by Steffans and Krishnan, who proposed diagnostic criteria based on known stroke or transient acute vascular event, radiological findings of hyperintensity, cortical or subcortical infarcts, age of onset after 50 years, and reduction in cognitive, executive, and information-processing speed [77]. The efficacy, in these patients, of typical and atypical antipsychotics, antidepressants, and mood stabilizers [78], also tested by us, raises the interesting question, to be explored in future studies, of the mechanism by which vascular dysfunction affects neurotransmissions’ dopaminergic, serotonergic, and membrane activity. Our work adds some data in the context of uncertainty and interest where there is a lack of large longitudinal observational studies, which is certainly difficult due to the complexity of the patients. Our results could be useful for a progressive demonstration of the causal relationship between vascular pathology and VLOSLP and therefore the definitive validation of “Vascular Schizophrenia-Like Psychosis” (Figure 1) in research and clinical practice.

Author Contributions

Conceptualization, M.L.; methodology, M.L. and G.D.; validation, M.L., G.D. and A.l.T.; formal analysis, G.D.; investigation, G.D., F.C. and L.C.; data curation, G.D., A.l.T., V.A. and C.G.; writing—original draft preparation, M.L. and G.D.; writing—review and editing, G.D.; visualization, F.C., A.l.T. and L.C.; supervision, A.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Italian Ministry of Health (Ricerca Corrente programme 2022 2024).

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Fondazione IRCCS Casa Sollievo della Sofferenza (Prot. N. 3877/DS).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Insel, T.R. Rethinking schizophrenia. Nature 2010, 468, 187–193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Rossler, W.; Salize, H.J.; van Os, J.; Riecher-Rossler, A. Size of burden of schizophrenia and psychotic disorders. Eur. Neuropsychopharmacol. 2005, 15, 399–409. [Google Scholar] [CrossRef]
  3. Jordan, G.; MacDonald, K.; Pope, M.A.; Schorr, E.; Malla, A.K.; Iyer, S.N. Positive changes experienced after a first episode of psychosis: A systematic review. Psychiatr. Serv. 2018, 69, 84–99. [Google Scholar] [CrossRef] [PubMed]
  4. Maglione, J.E.; Thomas, S.E.; Jeste, D.V. Late-onset schizophrenia: Do recent studies support categorizing LOS as a subtype of schizophrenia? Curr. Opin. Psychiatry 2014, 27, 173–178. [Google Scholar] [CrossRef] [Green Version]
  5. Jeste, D.V.; Blazer, D.G.; First, M. Aging-related diagnostic variations: Need for diagnostic criteria appropriate for elderly psychiatric patients. Biol. Psychiatry 2005, 58, 265–271. [Google Scholar] [CrossRef]
  6. Mühlbauer, V.; Möhler, R.; Dichter, M.N.; Zuidema, S.U.; Köpke, S.; Luijendijk, H.J. Antipsychotics for agitation and psychosis in people with Alzheimer’s disease and vascular dementia. Cochrane Database Syst. Rev. 2021, 12, CD013304. [Google Scholar] [CrossRef]
  7. Kessler, R.C.; Amminger, G.P.; Aguilar-Gaxiola, S.; Alonso, J.; Lee, S.; Ustün, T.B. Age of onset of mental disorders: A review of recent literature. Curr. Opin. Psychiatry 2007, 20, 359–364. [Google Scholar] [CrossRef]
  8. Blöchl, M.; Schaare, H.L.; Kunzmann, U.; Nestler, S. The Age-Dependent Association between Vascular Risk Factors and Depressed Mood. J. Gerontol. B Psychol. Sci. Soc. Sci. 2022, 77, 284–294. [Google Scholar] [CrossRef]
  9. Mast, B.T.; Neufeld, S.; MacNeill, S.E.; Lichtenberg, P.A. Longitudinal support for the relationship between vascular risk factors and late-life depressive symptoms. Am. J. Geriatr. Psychiatry 2004, 12, 93–101. [Google Scholar] [CrossRef]
  10. Howard, R.; Cox, T.; Almeida, O.; Mullen, R.; Graves, P.; Reveley, A.; Levy, R. White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly. Biol. Psychiatry 1995, 38, 86–91. [Google Scholar] [CrossRef]
  11. Kim, J.T.; Park, M.S.; Yoon, G.J.; Jung, H.J.; Choi, K.H.; Nam, T.S.; Lee, S.H.; Choi, S.M.; Kim, B.C.; Kim, M.K.; et al. White matter hyperintensity as a factor associated with delayed mood disorders in patients with acute ischemic stroke. Eur. Neurol. 2011, 66, 343–349. [Google Scholar] [CrossRef] [PubMed]
  12. Lebedeva, A.; Sundström, A.; Lindgren, L.; Stomby, A.; Aarsland, D.; Westman, E.; Winblad, B.; Olsson, T.; Nyberg, L. Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus. Acta Psychiatr. Scand. 2018, 137, 491–502. [Google Scholar] [CrossRef] [PubMed]
  13. Utumi, Y.; Iseki, E.; Arai, H. Three patients with mood disorders showing catatonia and frontotemporal lobes atrophy. Psychogeriatrics 2013, 13, 254–259. [Google Scholar] [CrossRef] [Green Version]
  14. Breitner, J.C.; Husain, M.M.; Figiel, G.S.; Krishnan, K.R.; Boyko, O.B. Cerebral white matter disease in late-onset paranoid psychosis. Biol. Psychiatry 1990, 28, 266–274. [Google Scholar] [CrossRef]
  15. Jeste, D.V.; McAdams, L.A.; Palmer, B.W.; Braff, D.; Jernigan, T.L.; Paulsen, J.S.; Stout, J.C.; Symonds, L.L.; Bailey, A.; Heaton, R.K. Relationship of neuropsychological and MRI measures to age of onset of schizophrenia. Acta Psychiatr. Scand. 1998, 98, 156–164. [Google Scholar] [CrossRef] [Green Version]
  16. Swayze, V.W., 2nd; Andreasen, N.C.; Alliger, R.J.; Yuh, W.T.; Ehrhardt, J.C. Subcortical and temporal structures in affective disorder and schizophrenia: A magnetic resonance imaging study. Biol. Psychiatry 1992, 31, 221–240. [Google Scholar] [CrossRef] [PubMed]
  17. Jørgensen, L.R.; Hegtmann, C.L.; Straszek, S.P.V.; Høyer, C.; Polcwiartek, C.; Petersen, L.J.; Dalgaard, M.K.; Jensen, S.E.; Nielsen, R.E. Peripheral artery disease in patients with schizophrenia as compared to controls. BMC Cardiovasc. Disord. 2023, 23, 126. [Google Scholar] [CrossRef]
  18. Wilkowska, A.; Kujawska-Danecka, H.; Hajduk, A. Risk and prophylaxis of venous thromboembolism in hospitalized psychiatric patients. A review. Psychiatr. Pol. 2018, 52, 421–435. [Google Scholar] [CrossRef]
  19. van der Heijden, F.M.; Zeebregts, C.J.; Reijnen, M.M. Does extracranial arterial pathology play a role in late-onset psychiatric disorders? Cogn. Behav. Neurol. 2010, 23, 147–151. [Google Scholar] [CrossRef]
  20. Osby, U.; Westman, J.; Hallgren, J.; Gissler, M. Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987–2010. Eur. J. Public Health 2016, 26, 867–871. [Google Scholar] [CrossRef] [Green Version]
  21. Fan, Z.; Wu, Y.; Shen, J.; Ji, T.; Zhan, R. Schizophrenia and the risk of cardiovascular diseases: A meta-analysis of thirteen cohort studies. J. Psychiatr. Res. 2013, 47, 1549–1556. [Google Scholar] [CrossRef] [PubMed]
  22. Moises, H.W.; Wollschläger, D.; Binder, H. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder. Transl. Psychiatry 2015, 5, e616. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Brandes, R.P.; Fleming, I.; Busse, R. Endothelial aging. Cardiovasc. Res. 2005, 66, 286–294. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Seals, D.R.; Jablonski, K.L.; Donato, A.J. Aging and vascular endothelial function in humans. Clin. Sci. 2011, 120, 357–375. [Google Scholar] [CrossRef] [Green Version]
  25. Müller, N. Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations. Schizophr. Bull. 2018, 44, 973–982. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Korann, V.; Suhas, S.; Appaji, A.; Nagendra, B.; Padmanabha, A.; Jacob, A.; Devi, P.; Bharath, R.D.; Kumar, V.; Varambally, S.; et al. Association between retinal vascular measures and brain white matter lesions in schizophrenia. Asian J. Psychiatr. 2022, 70, 103042. [Google Scholar] [CrossRef]
  27. Ermakov, E.A.; Dmitrieva, E.M.; Parshukova, D.A.; Kazantseva, D.V.; Vasilieva, A.R.; Smirnova, L.P. Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives. Oxid. Med. Cell Longev. 2021, 2021, 8881770. [Google Scholar] [CrossRef]
  28. Nguyen, T.T.; Dev, S.I.; Chen, G.; Liou, S.C.; Martin, A.S.; Irwin, M.R.; Carroll, J.E.; Tu, X.; Jeste, D.V.; Eyler, L.T. Abnormal levels of vascular endothelial biomarkers in schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 2018, 268, 849–860. [Google Scholar] [CrossRef] [Green Version]
  29. Howard, R.; Rabins, P.V.; Seeman, M.V.; Jeste, D.V. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: An international consensus. The International Late-Onset Schizophrenia Group. Am. J. Psychiatry 2000, 157, 172–178. [Google Scholar] [CrossRef]
  30. Sachdev, P.S.; Mohan, A.; Taylor, L.; Jeste, D.V. DSM-5 and Mental Disorders in Older Individuals: An Overview. Harv. Rev. Psychiatry 2015, 23, 320–328. [Google Scholar] [CrossRef]
  31. Chen, L.; Selvendra, A.; Stewart, A.; Castle, D. Risk factors in early and late onset schizophrenia. Compr. Psychiatry 2018, 80, 155–162. [Google Scholar] [CrossRef] [PubMed]
  32. Howard, R.J.; Graham, C.; Sham, P.; Dennehey, J.; Castle, D.J.; Levy, R.; Murray, R. A controlled family study of late-onset non-affective psychosis (late paraphrenia). Br. J. Psychiatry 1997, 170, 511–514. [Google Scholar] [CrossRef] [PubMed]
  33. Meesters, P.D.; de Haan, L.; Comijs, H.C.; Stek, M.L.; Smeets-Janssen, M.M.; Weeda, M.R.; Eikelenboom, P.; Smit, J.H.; Beekman, A.T. Schizophrenia spectrum disorders in later life: Prevalence and distribution of age at onset and sex in a dutch catchment area. Am. J. Geriatr. Psychiatry 2012, 20, 18–28. [Google Scholar] [CrossRef]
  34. Hanssen, M.; van der Werf, M.; Verkaaik, M.; Arts, B.; Myin-Germeys, I.; van Os, J.; Verhey, F.; Köhler, S.; Genetic Risk and Outcome in Psychosis Study Group. Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders. Am. J. Geriatr. Psychiatry 2015, 23, 852–862. [Google Scholar] [CrossRef] [PubMed]
  35. Reeves, S.; Stewart, R.; Howard, R. Service contact and psychopathology in very-late-onset schizophrenia-like psychosis: The effects of gender and ethnicity. Int. J. Geriatr. Psychiatry 2002, 17, 473–479. [Google Scholar] [CrossRef]
  36. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; (DSM-5); American Psychiatric Publishing: Arlington, VA, USA, 2013. [Google Scholar]
  37. Folstein, M.; Folstein, S.; McHugh, P. Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975, 12, 189–198. [Google Scholar] [CrossRef]
  38. Cummings, J.; Mega, M.; Gray, K.; Rosenberg-Thompson, S.; Carusi, D.; Gornbein, J. The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994, 44, 2308–2314. [Google Scholar] [CrossRef] [Green Version]
  39. Katz, S.; Downs, T.; Cash, H.; Grotz, R. Progress in the development of an index of ADL. Gerontologist 1970, 10, 20–30. [Google Scholar] [CrossRef]
  40. Lawton, M.; Brody, E. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 1969, 9, 179–186. [Google Scholar] [CrossRef]
  41. Gabb, G.M.; Mangoni, A.A.; Arnolda, L. Guideline for the diagnosis and management of hypertension in adults—2016. Med. J. Aust. 2017, 206, 141. [Google Scholar] [CrossRef]
  42. Jellinger, P.S.; Handelsman, Y.; Rosenblit, P.D.; Bloomgarden, Z.T.; Fonseca, V.A.; Garber, A.J.; Grunberger, G.; Guerin, C.K.; Bell, D.S.H.; Mechanick, J.I.; et al. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines For Management of Dyslipidemia And Prevention of Cardiovascular Disease. Endocr. Pr. 2017, 23, 1–87. [Google Scholar] [CrossRef] [Green Version]
  43. Garber, A.J.; Abrahamson, M.J.; Barzilay, J.I.; Blonde, L.; Bloomgarden, Z.T.; Bush, M.A.; Dagogo-Jack, S.; DeFronzo, R.A.; Einhorn, D.; Fonseca, V.A.; et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm—2017 Executive Summary. Endocr. Pr. 2017, 23, 207–238. [Google Scholar] [CrossRef] [Green Version]
  44. Talonen, S.; Väänänen, J.; Kaltiala-Heino, R. Gender differences in first onset Schizophrenia spectrum psychoses. Nord. J. Psychiatry 2017, 71, 131–138. [Google Scholar] [CrossRef]
  45. Seeman, M.V. Sex differences in schizophrenia relevant to clinical care. Expert. Rev. Neurother. 2021, 21, 443–453. [Google Scholar] [CrossRef] [PubMed]
  46. Huang, Y.C.; Hung, C.F.; Lin, P.Y.; Lee, Y.; Wu, C.C.; Hsu, S.T.; Chen, C.C.; Chong, M.Y.; Lin, C.H.; Wang, L.J. Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids. Psychoneuroendocrinology 2017, 84, 87–93. [Google Scholar] [CrossRef] [PubMed]
  47. Wolters, F.J.; de Bruijn, R.F.; Hofman, A.; Koudstaal, P.J.; Ikram, M.A.; Heart Brain Connection Collaborative Research Group. Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia: A Population-Based Study. Arter. Thromb. Vasc. Biol. 2016, 36, 204–210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Smith, A.D.; Refsum, H.; Bottiglieri, T.; Fenech, M.; Hooshmand, B.; McCaddon, A.; Miller, J.W.; Rosenberg, I.H.; Obeid, R. Homocysteine and Dementia: An International Consensus Statement. J. Alzheimers Dis. 2018, 62, 561–570. [Google Scholar] [CrossRef] [Green Version]
  49. McCulloch, Y.; Clare, L.; Howard, R.; Peters, E. Psychological processes underlying delusional thinking in late-onset psychosis: A preliminary investigation. Int. J. Geriatr. Psychiatry 2006, 21, 768–777. [Google Scholar] [CrossRef] [PubMed]
  50. Giblin, S.; Clare, L.; Livingston, G.; Howard, R. Psychosocial correlates of late-onset psychosis: Life experiences, cognitive schemas, and attitudes to ageing. Int. J. Geriatr. Psychiatry 2004, 19, 611–623. [Google Scholar] [CrossRef]
  51. Jones, D.K.; Catani, M.; Pierpaoli, C.; Reeves, S.J.; Shergill, S.S.; O’Sullivan, M.; Maguire, P.; Horsfield, M.A.; Simmons, A.; Williams, S.C.; et al. A diffusion tensor magnetic resonance imaging study of frontal cortex connections in very-late-onset schizophrenia-like psychosis. Am. J. Geriatr. Psychiatry 2005, 13, 1092–1099. [Google Scholar] [CrossRef]
  52. Barak, Y.; Aizenberg, D.; Mirecki, I.; Mazeh, D.; Achiron, A. Very late-onset schizophrenia-like psychosis: Clinical and imaging characteristics in comparison with elderly patients with schizophrenia. J. Nerv. Ment. Dis. 2002, 190, 733–736. [Google Scholar] [CrossRef]
  53. Van Assche, L.; Van Aubel, E.; Van de Ven, L.; Bouckaert, F.; Luyten, P.; Vandenbulcke, M. The Neuropsychological Profile and Phenomenology of Late Onset Psychosis: A Cross-sectional Study on the Differential Diagnosis of Very-Late-Onset Schizophrenia-Like Psychosis, Dementia with Lewy Bodies and Alzheimer’s Type Dementia with Psychosis. Arch. Clin. Neuropsychol. 2019, 34, 183–199. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Moore, R.; Blackwood, N.; Corcoran, R.; Rowse, G.; Kinderman, P.; Bentall, R.; Howard, R. Misunderstanding the intentions of others: An exploratory study of the cognitive etiology of persecutory delusions in very late-onset schizophrenia-like psychosis. Am. J. Geriatr. Psychiatry 2006, 14, 410–418. [Google Scholar] [CrossRef] [PubMed]
  55. Harris, B.S.; Kotsopoulos, E.J.; Yamin, S. Phenotypic cognitive impairment in late-onset delusional disorder. Int. Psychogeriatr. 2014, 26, 965–975. [Google Scholar] [CrossRef]
  56. Brodaty, H.; Sachdev, P.; Koschera, A.; Monk, D.; Cullen, B. Long-term outcome of late-onset schizophrenia: 5-year follow-up study. Br. J. Psychiatry 2003, 183, 213–219. [Google Scholar] [CrossRef] [Green Version]
  57. Bravo Baptista, S.; Faustino, M.; Brizida, L.; Loureiro, J.; Augusto, J.; Abecasis, J.; Monteiro, C.; Leal, P.; Nédio, M.; Farto, E.; et al. Early peripheral endothelial dysfunction predicts myocardial infarct extension and microvascular obstruction in patients with ST-elevation myocardial infarction. Rev. Port. Cardiol. 2017, 36, 731–742. [Google Scholar] [CrossRef]
  58. Israel, A.K.; Seeck, A.; Boettger, M.K.; Rachow, T.; Berger, S.; Voss, A.; Bär, K.J. Peripheral endothelial dysfunction in patients suffering from acute schizophrenia: A potential marker for cardiovascular morbidity? Schizophr. Res. 2011, 128, 44–50. [Google Scholar] [CrossRef]
  59. Protopopova, D.; Masopust, J.; Malý, R.; Valis, M.; Dostalova, G.; Ranna, K.; Bažant, J. Peripheral endothelial dysfunction as a marker of cardiovascular risk in physically healthy patients with schizophrenia and related psychoses: A matched case control study. Neuro Endocrinol. Lett. 2014, 35, 503–509. [Google Scholar]
  60. Radu, G.; Luca, C.; Petrescu, L.; Bordejevic, D.A.; Tomescu, M.C.; Andor, M.; Cîtu, I.; Mavrea, A.; Buda, V.; Tomescu, C.; et al. The Predictive Value of Endothelial Inflammatory Markers in the Onset of Schizophrenia. Neuropsychiatr. Dis. Treat. 2020, 16, 545–555. [Google Scholar] [CrossRef] [Green Version]
  61. Lyness, J.M.; King, D.A.; Conwell, Y.; Cox, C.; Caine, E.D. Cerebrovascular risk factors and 1-year depression outcome in older primary care patients. Am. J. Psychiatry 2000, 157, 1499–1501. [Google Scholar] [CrossRef] [PubMed]
  62. Massardo, T.; Quintana, J.C.; Jaimovich, R.; Sáez, C.G.; Risco, L.; Liberman, C.; Araya, A.V.; Galleguillos, T.; Castro-Mora, G.; Pereira, J. Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder. Neuropsychobiology 2021, 80, 214–224. [Google Scholar] [CrossRef] [PubMed]
  63. Wake, R.; Miyaoka, T.; Araki, T.; Kawakami, K.; Furuya, M.; Limoa, E.; Hashioka, S.; Horiguchi, J. Regional cerebral blood flow in late-onset schizophrenia: A SPECT study using 99mTc-ECD. Eur. Arch. Psychiatry Clin. Neurosci. 2016, 266, 3–12. [Google Scholar] [CrossRef]
  64. Najjar, S.; Pahlajani, S.; De Sanctis, V.; Stern, J.N.H.; Najjar, A.; Chong, D. Neurovascular Unit Dysfunction and Blood-Brain Barrier Hyperpermeability Contribute to Schizophrenia Neurobiology: A Theoretical Integration of Clinical and Experimental Evidence. Front. Psychiatry 2017, 8, 83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006, 7, 41–53. [Google Scholar] [CrossRef]
  66. Friedman, A.; Kaufer, D. Blood-brain barrier breakdown and blood-brain communication in neurological and psychiatric diseases. Cardiovasc. Psychiatry Neurol. 2011, 2011, 431470. [Google Scholar] [CrossRef] [Green Version]
  67. Uranova, N.A.; Zimina, I.S.; Vikhreva, O.V.; Krukov, N.O.; Rachmanova, V.I.; Orlovskaya, D.D. Ultrastructural damage of capillaries in the neocortex in schizophrenia. World J. Biol. Psychiatry 2010, 11, 567–578. [Google Scholar] [CrossRef]
  68. Pun, P.B.; Lu, J.; Moochhala, S. Involvement of ROS in BBB dysfunction. Free Radic. Res. 2009, 43, 348–364. [Google Scholar] [CrossRef]
  69. Yarlagadda, A.; Alfson, E.; Clayton, A.H. The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry 2009, 6, 18–22. [Google Scholar]
  70. Harris, L.W.; Wayland, M.; Lan, M.; Ryan, M.; Giger, T.; Lockstone, H.; Wuethrich, I.; Mimmack, M.; Wang, L.; Kotter, M.; et al. The cerebral microvasculature in schizophrenia: A laser capture microdissection study. PLoS ONE 2008, 3, e3964. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  71. Khandaker, G.M.; Dantzer, R. Is there a role for immune-to-brain communication in schizophrenia? Psychopharmacology 2016, 233, 1559–1573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Jin, R.; Song, Z.; Yu, S.; Piazza, A.; Nanda, A.; Penninger, J.M.; Granger, D.N.; Li, G. Phosphatidylinositol-3-kinase gamma plays a central role in blood-brain barrier dysfunction in acute experimental stroke. Stroke 2011, 42, 2033–2044. [Google Scholar] [CrossRef] [PubMed]
  73. Henninger, D.D.; Panés, J.; Eppihimer, M.; Russell, J.; Gerritsen, M.; Anderson, D.C.; Granger, D.N. Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse. J. Immunol. 1997, 158, 1825–1832. [Google Scholar] [CrossRef] [PubMed]
  74. Lencz, T.; Guha, S.; Liu, C.; Rosenfeld, J.; Mukherjee, S.; DeRosse, P.; John, M.; Cheng, L.; Zhang, C.; Badner, J.A.; et al. Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. Nat. Commun. 2013, 4, 2739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Alexopoulos, G.S.; Meyers, B.S.; Young, R.C.; Campbell, S.; Silbersweig, D.; Charlson, M. ’Vascular depression’ hypothesis. Arch. Gen. Psychiatry 1997, 54, 915–922. [Google Scholar] [CrossRef]
  76. Wijeratne, C.; Malhi, G.S. Vascular mania: An old concept in danger of sclerosing? A clinical overview. Acta Psychiatr. Scand. Suppl. 2007, 434, 35–40. [Google Scholar] [CrossRef]
  77. Steffens, D.C.; Krishnan, K.R. Structural neuroimaging and mood disorders: Recent findings, implications for classification, and future directions. Biol. Psychiatry 1998, 43, 705–712. [Google Scholar] [CrossRef]
  78. Fischer, C.E.; Namasivayam, A.; Crawford-Holland, L.; Hakobyan, N.; Schweizer, T.A.; Munoz, D.G.; Pollock, B.G. Psychotic Disorders in the Elderly: Diagnosis, Epidemiology, and Treatment. Psychiatr. Clin. North Am. 2022, 45, 691–705. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Flow chart of possible mechanisms of Vascular Schizophrenia-Like Psychosis.
Figure 1. Flow chart of possible mechanisms of Vascular Schizophrenia-Like Psychosis.
Jcm 12 04831 g001
Table 1. Demographic, cognitive, functional, and neuropsychiatric characteristics of patients according to gender.
Table 1. Demographic, cognitive, functional, and neuropsychiatric characteristics of patients according to gender.
ALL
N = 103
Male
N = 39
Female
N = 64
p-Value
Age (years) 0.639
Mean ± SD80.32 ± 7.6580.78 ± 8.0880.04 ± 7.42
Range65.00–95.3665.00–95.3665.00–93.45
MMSE 0.727
Mean ± SD20.55 ± 5.9820.81 ± 7.1820.39 ± 5.17
Range0–30.000–30.000–30.00
ADL 0.348
Mean ± SD4.57 ± 1.584.38 ± 1.564.69 ± 1.59
Range1.00–6.002.00–6.001.00–6.00
IADL 0.415
Mean ± SD3.38 ± 2.923.08 ± 2.753.56 ± 3.02
Range0–8.000–8.000–8.00
NPI—Total score 0.770
Mean ± SD40.73 ± 22.3939.90 ± 19.6441.23 ± 24.04
Range4.00–100.006.00–84.004.00–100.00
NPI—Distress
Mean ± SD15.78 ± 7.3314.82 ± 7.1816.36 ± 7.410.304
Range0–38.000–32.004.00–38.00
NPI—Delusion
Mean ± SD5.11 ± 4.745.00 ± 4.585.17 ± 4.860.859
Range0–12.000–12.000–12.00
NPI—Hallucination
Mean ± SD4.73 ± 4.853.56 ± 4.485.44 ± 4.970.057
Range0–15.000–15.000–15.00
NPI—Agitation/Aggresion
Mean ± SD5.57 ± 4.276.44 ± 4.435.05 ± 4.110.109
Range0–16.000–16.000–12.00
NPI—Depression
Mean ± SD5.40 ± 4.385.13 ± 4.675.56 ± 4.220.628
Range0–16.000–16.000–12.00
NPI—Anxiety
Mean ± SD3.93 ± 4.623.44 ± 4.764.23 ± 4.540.397
Range0–16.000–16.000–12.00
NPI—Euphoria
Mean ± SD0.88 ± 2.870.62 ± 2.381.05 ± 3.140.462
Range0–12.000–12.000–12.00
NPI—Apathy
Mean ± SD4.89 ± 4.753.67 ± 4.625.64 ± 4.710.040
Range0–12.000–12.000–12.00
NPI—Disinhibition
Mean ± SD0.79 ± 2.300.82 ± 2.320.77 ± 2.310.907
Range0–9.000–9.000–9.00
NPI—Irritability
Mean ± SD5.04 ± 4.625.62 ± 5.084.69 ± 4.310.325
Range0–16.000–16.000–12.00
NPI—Abnormal activity
Mean ± SD1.01 ± 2.700.87 ± 2.321.09 ± 2.930.688
Range0–12.000–9.000–12.00
NPI—Sleep disturbance
Mean ± SD4.97 ± 4.244.28 ± 3.955.39 ± 4.380.189
Range0–12.000–9.000–12.00
NPI—Eating disorders
Mean ± SD1.86 ± 3.621.03 ± 2.662.38 ± 4.030.066
Range0–12.000–12.000–12.00
Psychosis
Affective—n (%)76(73.8)26(34.2)50(65.8)0.200
No-affective—n (%)27(26.2)13(48.1)14(51.9)
Legend: MMSE, Mini-Mental State Examination; ADL, Activities of Daily Living; IADL, Instrumental Activities of Daily Living; NPI, Neuropsychiatric Inventory.
Table 2. Clinical and lifestyle characteristics of patients according to gender.
Table 2. Clinical and lifestyle characteristics of patients according to gender.
ALL
N = 103
Male
N = 39
Female
N = 64
p-Value
Laboratory measurements
ApoE
ε2/ε3–N (%)6 (5.8)3 (7.7)3 (4.7)
ε3/ε3–N (%)61 (59.2)24 (61.5)37 (57.8)0.862
ε3/ε4–N (%)27 (26.2)9 (23.1)18 (28.1)
ε4/ε4–N (%)9 (8.7)3 (7.7)6 (9.4)
Hb, g/dL 0.019
Mean ± SD13.40 ± 1.5213.85 ± 1.6213.13 ± 1.39
Range10.00–18.0010.00–18.0010.00–17.00
MCV, fL 0.195
Mean ± SD90.84 ± 6.5591.91 ± 6.5890.18 ± 6.50
Range59.00–100.0065.00–100.0059.00–100.00
Platelets, mil/mcl 0.004
Mean ± SD220.94 ± 79.94192.15 ± 61.82238.48 ± 84.94
Range21.00–595.0021.00–367.00119.00–595.00
TPT, g/dL 0.768
Mean ± SD6.99 ± 0.716.96 ± 0.637.01 ± 0.75
Range5.00–9.005.00–8.005.00–9.00
Creatinine, mg/dL 0.406
Mean ± SD1.01 ± 0.361.04 ± 0.330.98 ± 0.38
Range0–3.001.00–2.000–3.00
Azotemia, mg/dL
Mean ± SD45.95 ± 16.8145.64 ± 17.4946.14 ± 16.530.884
Range21.00–106.0021.00–105.0022.00–106.00
Glycemia, mg/dL
Mean ± SD96.90 ± 24.5695.15 ± 21.4097.98 ± 26.440.574
Range68.00–187.0068.00–164.0071.00–187.00
TC, mg/dL
Mean ± SD183.46 ± 45.21175.33 ± 46.09188.41 ± 44.300.156
Range97.00–301.00106.00–301.0097.00–298.00
TG, mg/dL
Mean ± SD114.83 ± 85.66130.79 ± 128.31105.09 ± 41.200.140
Range39.00–835.0042.00–835.0039.00–311.00
UA, mg/dL
Mean ± SD4.90 ± 1.555.53 ± 1.524.53 ± 1.460.001
Range2.00–10.002.00–10.002.00–9.00
Na, mmol/L
Mean ± SD140.57 ± 3.60139.95 ± 3.03140.95 ± 3.880.171
Range120.00–147.00133.00–146.00120.00–147.00
K, mmol/L
Mean ± SD4.28 ± 0.634.25 ± 0.404.29 ± 0.740.780
Range3.00–8.004.00–5.003.00–8.00
Cl, mmol/L
Mean ± SD104.89 ± 3.67104.82 ± 2.94104.94 ± 4.080.876
Range87.00–116.0087.00–116.0087.00–116.00
Ca, mg/dL
Mean ± SD9.04 ± 0.598.82 ± 0.489.17 ± 0.610.003
Range8.00–11.008.00–10.008.00–11.00
Folate, ng/mL
Mean ± SD7.62 ± 6.567.20 ± 7.267.93 ± 6.060.629
Range2.00–41.002.00–41.002.00–41.00
Vit-B12, pg/mL
Mean ± SD371.04 ± 286.85323.91 ± 205.32405.60 ± 333.330.216
Range60.00–2000.0060.00–806.0098.00–2000.00
Homocysteine, μmol/L
Mean ± SD12.58 ± 5.3413.97 ± 6.8311.66 ± 3.900.100
Range4.00–28.004.00–28.005.00–20.00
Vascular risks
Hypertension
Yes—N (%)57 (55.3)20 (51.3)37 (57.8)0.518
No—N (%)46 (44.7)19 (48.7)27 (42.2)
Hyperlipidemia in treatment
Yes—N (%)22 (21.4)7 (17.9)15 (23.4)0.510
No—N (%)81 (78.6)32 (82.1)49 (76.6)
Diabetes
Yes—N (%)20 (19.4)6 (15.4)14 (21.9)0.419
No—N (%)83 (80.6)33 (84.6)50 (78.1)
AF
Yes—N (%)11 (10.7)5 (12.8)6 (9.4)0.583
No—N (%)92 (89.3)34 (87.2)58 (90.6)
HF
Yes—N (%)8 (7.8)4 (10.3)4 (6.2)0.461
No—N (%)95 (92.2)35 (89.7)60 (93.8)
Stroke
Yes—N (%)15 (14.6)6 (15.4)9 (14.1)0.854
No—N (%)88 (85.4)33 (84.6)55 (85.9)
MI
Yes—N (%)13 (12.6)5 (12.8)8 (12.5)0.962
No—N (%)90 (87.4)34 (87.2)56 (87.5)
Tobacco use
Yes—N (%)5 (4.9)4 (10.3)1 (1.6)0.046
No—N (%)98 (95.1)35 (89.7)63 (98.4)
Alcohol consumption
Yes—N (%)3 (2.9)3 (7.7)0 0.024
No—N (%)100 (97.1)36 (92.3)64 (100.0)
Legend: ApoE, apolipoprotein E; Hb, hemoglobin; MCV, mean corpuscular volume; TPT, total protein test; TC, total cholesterol; TG, triglycerides; UA, uric acid; Na, sodium; K, potassium; Cl, chlorine; Ca, calcium; Vit-B12, vitamin B12; AF, atrial fibrillation; HF, heart failure; MI, myocardial infarction.
Table 3. Frequency of vascular risk factors in patients less than and more than 80 years old, per gender.
Table 3. Frequency of vascular risk factors in patients less than and more than 80 years old, per gender.
<80 Years≥80 Yearsp-Value
Males
Hypertension
Yes—N (%)8 (44.4)12 (57.1)0.429
No—N (%)10 (55.6)9 (42.9)
Hyperlipidemia in treatment
Yes—N (%)4 (22.2)3 (14.3)0.520
No—N (%)14 (77.8)18 (85.7)
Diabetes
Yes—N (%)4 (22.2)2 (9.5)0.273
No—N (%)14 (77.8)19 (90.5)
AF
Yes—N (%)1 (5.6)4 (19.0)0.209
No—N (%)17 (94.4)17 (81.0)
HF
Yes—N (%)2 (11.1)2 (9.5)0.871
No—N (%)16 (88.9)19 (90.5)
Stroke
Yes—N (%)1 (5.6)5 (23.8)0.115
No—N (%)17 (94.4)16 (76.2)
MI
Yes—N (%)05 (23.8)0.027
No—N (%)18 (100.0)16 (76.2)
Tobacco use
Yes—N (%)3 (16.7)1 (4.8)0.222
No—N (%)15 (83.3)20 (95.2)
Alcohol consumption
Yes—N (%)1 (5.6)2 (9.5) 0.643
No—N (%)17 (94.4)19 (90.5)
Females
Hypertension
Yes—N (%)16 (53.3)21 (61.8)0.496
No—N (%)14 (46.7)13 (38.2)
Dyslipidemia
Yes—N (%)9 (30.0)6 (17.6)0.244
No—N (%)21 (70.0)28 (82.4)
Diabetes
Yes—N (%)9 (30.0)5 (14.7)0.140
No—N (%)21 (70.0)29 (85.3)
AF
Yes—N (%)1 (3.3)5 (14.7)0.119
No—N (%)29 (96.7)29 (85.3)
HF
Yes—N (%)04 (11.8)0.052
No—N (%)30 (100.0)30 (88.2)
Stroke
Yes—N (%)5 (16.7)4 (11.8)0.573
No—N (%)25 (83.3)30 (88.2)
MI
Yes—N (%)2 (6.7)6 (17.6)0.185
No—N (%)28 (93.3)28 (82.4)
Tobacco use
Yes—N (%)1 (3.3)00.283
No—N (%)29 (96.7)34 (100.0)
Alcohol consumption
Yes—N (%)00 1.000
No—N (%)30 (100.0)34 (100.0)
Legend: AF, atrial fibrillation; HF, heart failure; MI, myocardial infarction.
Table 4. Current use of antipsychotic and antidepressant drugs in our sample.
Table 4. Current use of antipsychotic and antidepressant drugs in our sample.
MedicationsAffective PsychosisNo-Affective Psychosisp-Value
Untreated—N (%)1 (1.3)00.549
Treated—N (%)75 (98.7)27 (100.0)
SSRI—N (%)21 (27.6)5 (18.5)0.349
AA—N (%)41 (53.9)17 (63.0)0.417
TA—N (%)9 (11.8)8 (29.6)0.032
MS—N (%)14 (18.4)1 (3.7)0.063
Tz—N (%)11 (14.5)2 (7.4)0.342
Legend: SSRI, selective serotonin reuptake inhibitors; AA, atypical antipsychotic; TA, typical antipsychotic; MS, mood stabilizers; Tz, trazodone.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Lauriola, M.; D’Onofrio, G.; Ciccone, F.; Torre, A.l.; Angelillis, V.; Germano, C.; Cascavilla, L.; Greco, A. Vascular Schizophrenia-like Psychosis in Older Adults. J. Clin. Med. 2023, 12, 4831. https://doi.org/10.3390/jcm12144831

AMA Style

Lauriola M, D’Onofrio G, Ciccone F, Torre Al, Angelillis V, Germano C, Cascavilla L, Greco A. Vascular Schizophrenia-like Psychosis in Older Adults. Journal of Clinical Medicine. 2023; 12(14):4831. https://doi.org/10.3390/jcm12144831

Chicago/Turabian Style

Lauriola, Michele, Grazia D’Onofrio, Filomena Ciccone, Annamaria la Torre, Valentina Angelillis, Carmela Germano, Leandro Cascavilla, and Antonio Greco. 2023. "Vascular Schizophrenia-like Psychosis in Older Adults" Journal of Clinical Medicine 12, no. 14: 4831. https://doi.org/10.3390/jcm12144831

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop