Vascular Schizophrenia-like Psychosis in Older Adults.

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.

CT-Detected MTA Score Related to Disability and Behavior in Older People with Cognitive Impairment.

Our study aims to investigate the relationship between medial temporal lobe atrophy (MTA) score, assessed by computed tomography (CT) scans, and functional impairment, cognitive deficit, and psycho-behavioral disorder severity. Overall, 239 (M = 92, F = 147; mean age of 79.3 ± 6.8 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. MTA was evaluated from 0 (no atrophy) to 4 (severe atrophy). The homocysteine serum was set to two levels: between 0 and 10 µmol/L, and >10 µmol/L. The cholesterol and glycemia blood concentrations were measured. Hypertension and atrial fibrillation presence/absence were collected. A total of 14 patients were MTA 0, 44 patients were MTA 1, 63 patients were MTA 2, 79 patients were MTA 3, and 39 patients were MTA 4. Cognitive (p < 0.0001) and functional (p < 0.0001) parameters decreased according to the MTA severity. According to the diagnosis distribution, AD patient percentages increased by MTA severity (p < 0.0001). In addition, the homocysteine levels increased according to MTA severity (p < 0.0001). Depression (p < 0.0001) and anxiety (p = 0.001) increased according to MTA severity. This study encourages and supports the potential role of MTA score and CT scan in the field of neurodegenerative disorder research and diagnosis.

Relationship of Homocysteine Plasma Levels with Mild Cognitive Impairment, Alzheimer's Disease, Vascular Dementia, Psychobehavioral, and Functional Complications.

BACKGROUND: Alzheimer's disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. OBJECTIVE: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. METHODS: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10µmol/L and > 10µmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. RESULTS: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p < 0.0001), than MCI and mild dementia. Poss-AD and VaD had a higher frequency of homocysteine > 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p < 0.0001), and functional impairment severity respectively for ADL (p < 0.0001) and IADL (p < 0.0001). CONCLUSION: Higher homocysteine level seems to be significantly related to cognitive impairment frequency and severity, possible AD and VaD, neuropsychiatric symptom severity, and functional impairment severity.

Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease.

BACKGROUND: Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. METHODS: We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. RESULTS: Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121-0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195-4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. CONCLUSIONS: More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.

Late-Life Depression versus Amnestic Mild Cognitive Impairment: Alzheimer's Disease Incidence in 4 Years of Follow-Up.

BACKGROUND/AIM: The aim of the study was to evaluate the prognostic power of late-life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for the onset of Alzheimer's disease (AD) within 4 years of follow-up. METHODS: We estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients suffering of LLD treated with antidepressants with good compliance, and 66 healthy control (HC) patients, followed for 4 years. RESULTS: The risk to develop AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60% deteriorated without depression, and 72.20% deteriorated with depression after 4 years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other dementia type. CONCLUSION: In our results, aMCI was the first predictive condition that increased the risk to develop AD. Depression is a potentially preventable medical condition across the lifespan and may be a modifiable risk factor.

Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia.

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na⁺: p < 0.001; K⁺: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r² = 0.0046, p = 0.77), ESS (r² = 0.0052, p = 0.54) and MNA (r² = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65⁻75 years, p = 0.001; 76⁻85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.

Executive Dysfunction Detected with the Frontal Assessment Battery in Alzheimer's Disease Versus Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) lead to progressive decline in executive function. We estimated the prevalence of executive dysfunction in AD and VaD patients, investigating cognitive, functional, and clinical correlates and also using a multidimensional approach based on a standardized comprehensive geriatric assessment (CGA). We included 215 patients (115 AD patients and 100 VaD patients) consecutively evaluated with a complete cognitive and affective assessment, a CGA, and the Frontal Assessment Battery (FAB) with six subtests investigating conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. The prevalence of dysexecutive syndrome screened with a FAB score <12 points was high in both AD (97 patients) and VaD (77 patients) (84.3% versus 77.0%, p = 0.171). AD patients were significantly younger, with higher grade of cognitive impairment and less severe comorbidity and polypharmacy than VaD patients. AD patients showed a significantly higher impairment in FAB total score and five FAB subtests (conceptualization, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy) than VaD patients. These findings were largely confirmed in a sub-analysis conducted subdividing the sample in mild and moderate-to-severe demented patients and suggesting that in moderate-to-severe AD there was higher impairment in FAB total score and four FAB subtests (conceptualization, sensitivity to interference, inhibitory control, and environmental autonomy). Executive dysfunction could be greater in AD patients with moderate-to-severe dementia compared to VaD patients, although our groups were also not matched for age, comorbidity or polypharmacy, which could also exert an effect.

Erythrocyte Associated Amyloid-ß as Potential Biomarker to Diagnose Dementia.

BACKGROUND: Although it is known that Alzheimer's disease (AD) is associated with the progressive accumulation of amyloid ß-peptide (Aß) in the human brain, its pathogenic role has to be completely clarified. Aß moves from the bloodbrain barrier to the plasma and an increased Aß production in brain could be associated with higher Aß concentrations in blood. A recent study has evaluated Aß40 and Aß42 levels in human red blood cells (RBCs) with evidence of agedependent higher Aß concentration in RBCs. OBJECTIVE: The aim of the study was to investigate if erythrocyte associated Aß (iAß) levels could be different in subjects affected by dementia in comparison with controls and according to the patient's cognitive impairment or different dementia subtypes. METHOD: To answer these questions we assessed iAß40 and iAß42 levels in 116 patients: 32 healthy controls, 39 with diagnosis of vascular dementia (VaD), 14 mild cognitive impairment (MCI) and 31 AD. RESULTS: In this population we found significant differences in iAß42 between controls and cognitive impaired patients. Moreover, iAß42 significantly differed between dementia vs MCI. AD also showed different iAß42 levels as compared to VaD. Conversely, no differences were found for iAß40. All the analyses were adjusted for potential confounders like age, gender and Hb concentration. A direct correlation between increasing iAß42 concentration and the progression of the cognitive decline using the MMSE score as continuous variable was also found. CONCLUSION: Our findings support the evidence that iAß42 could be an instrument to early recognize dementia and predict cognitive impairment.

Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach.

In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p <  0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality.