The Association between Intracranial Calcifications and Symptoms in Patients with Primary Familial Brain Calcification.

(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02-1.12, p < 0.01), gait ataxia (OR 1.06, 95%-CI 1.00-1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00-1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01-1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.

Amount and Distribution of Intracranial Calcification in Symptomatic and Asymptomatic Primary Familial Brain Calcification.

Background and Objectives: In clinical practice, it can be difficult to differentiate between intracranial calcifications related to primary familial brain calcification (PFBC) or aging. Also, little is known about the consequences of the amount of intracranial calcifications in patients with PFBC. Therefore, we aimed to compare the amount and distribution of intracranial calcifications in persons with PFBC with controls and between asymptomatic and symptomatic PFBC cases. Methods: This was a case-control study including patients with PFBC and controls. Controls received a CT of the brain because of a trauma and had at least some basal ganglia calcification. The Nicolas score and volume of calcification were used to quantify intracranial calcifications on the CT scans. Receiver operating characteristic curves were obtained to calculate optimal cutoff points to discriminate between cases and controls. Mann-Whitney U tests and logistic regression, adjusted for age and sex, were used to compare the amount of calcification. Results: Twenty-eight cases (median age 65 years, 50.0% male) and 90 controls (median age 74 years, 46.1% male) were included. Calcification scores were higher in cases (median volume: 4.91 cm3 against 0.03 cm3, p < 0.001, median Nicolas score: 26.5 against 2.0, p < 0.001) than controls. Calcifications were also more diffusely distributed in cases. To differentiate between cases and controls, optimal cutoff points were ≥0.2 cm3 for the calcification volume and ≥6.0 for the Nicolas score. Calcification was higher for symptomatic than asymptomatic cases (calcification volume: 13.62 cm3 against 1.61 cm3, p = 0.01, Nicolas score: 39.0 against 15.5, p = 0.02). After adjustment for age and sex, the Nicolas score remained significantly higher in symptomatic patients, and the calcification volume did not. Discussion: Patients with PFBC had more severe intracranial calcifications, and these calcifications were more diffusely distributed through the brain compared with controls. Symptomatic patients with PFBC might have more intracranial calcifications than asymptomatic persons.

Prevalence and Association of Basal Ganglia Calcifications and Depressive Symptoms in Patients With Mild Cognitive Impairment or Dementia.

AIM: The aim of this study is to investigate the association between basal ganglia calcification (BGC) and depressive symptoms within older adults with mild cognitive impairment (MCI) or dementia. METHODS: For this cross-sectional study, we included patients with MCI or dementia who visited the memory clinic between April 2009 and April 2015. All patients underwent a standard diagnostic workup, including assessment of depressive symptoms with the Geriatric Depression Scale and computed tomography imaging of the brain. Computed tomography scans were assessed for presence and severity of BGC. To analyse the association between BGC and depressive symptoms, binary logistic regression models were performed with adjustment for age, sex, cardiovascular risk factors, and cardiovascular diseases. RESULTS: In total, 1054 patients were included (median age: 81.0 y; 39% male). BGC was present in 44% of the patients, of which 20% was classified as mild, 20% as moderate, and 4% as severe. There were 223 patients (21%) who had a Geriatric Depression Scale score indicative of depressive symptoms. No association was found between the presence or severity of BGC and depressive symptoms. CONCLUSIONS: Although both BGC and depressive symptoms were common in patients with MCI or dementia, no association was demonstrated between the presence or severity of BGC and depressive symptoms.

Serum biomarkers for arterial calcification in humans: A systematic review.

Aim: To clarify the role of mediators of ectopic mineralization as biomarkers for arterial calcifications. Methods: MEDLINE and Embase were searched for relevant literature, until January 4th 2022. The investigated biomarkers were: calcium, phosphate, parathyroid hormone, vitamin D, pyrophosphate, osteoprotegerin, receptor activator of nuclear factor-kappa B ligand (RANKL), fibroblast growth factor-23 (FGF-23), Klotho, osteopontin, osteocalcin, Matrix Gla protein (MGP) and its inactive forms and vitamin K. Studies solely performed in patients with kidney insufficiency or diabetes mellitus were excluded. Results: After screening of 8985 articles, a total of 129 articles were included in this systematic review. For all biomarkers included in this review, the results were variable and more than half of the studies for each specific biomarker had a non-significant result. Also, the overall quality of the included studies was low, partly as a result of the mostly cross-sectional study designs. The largest body of evidence is available for phosphate, osteopontin and FGF-23, as a little over half of the studies showed a significant, positive association. Firm statements for these biomarkers cannot be drawn, as the number of studies was limited and hampered by residual confounding or had non-significant results. The associations of the other mediators of ectopic mineralization with arterial calcifications were not clear. Conclusion: Associations between biomarkers of ectopic mineralization and arterial calcification are variable in the published literature. Future longitudinal studies differentiating medial and intimal calcification could add to the knowledge of biomarkers and mechanisms of arterial calcifications.

Intracranial artery calcifications: Risk factors and association with cardiovascular disease and cognitive function.

BACKGROUND AND AIMS: we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. METHODS: patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. RESULTS: 1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p < 0.001), diabetes mellitus (medial iICA, p = 0.004), hypertension (intimal iICA, p < 0.001) and basilar artery, p = 0.019) and smoking (intimal iICA, p = 0.008). iICA calcifications were associated with stroke and intimal calcifications also with myocardial infarction. Intracranial artery calcifications were not associated with cognitive function or type of cognitive disorder. CONCLUSION: the majority of memory clinic patients had intracranial artery calcifications. Cardiovascular risk factors are differentially related to medial or intimal iICA calcifications. iICA calcifications were associated with myocardial infarction and stroke, but not with cognitive outcomes.

A prediction model for one- and three-year mortality in dementia: results from a nationwide hospital-based cohort of 50,993 patients in the Netherlands.

OBJECTIVE: to develop a model to predict one- and three-year mortality in patients with dementia attending a hospital, through hospital admission or day/memory clinic. DESIGN: we constructed a cohort of dementia patients through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register and the national cause of death register. SUBJECTS: patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010. METHODS: logistic regression analysis techniques were used to predict one- and three-year mortality after a first hospitalisation with dementia. The performance was assessed using the c-statistic and the Hosmer-Lemeshow test. Internal validation was performed using bootstrap resampling. RESULTS: 50,993 patients were included in the cohort. Two models were constructed, which included age, sex, setting of care (hospitalised versus day clinic) and the presence of comorbidity using the Charlson comorbidity index. One model predicted one-year mortality and the other three-year mortality. Model discrimination according to the c-statistic for the models was 0.71 (95% CI 0.71-0.72) and 0.72 (95% CI 0.72-0.73), respectively. CONCLUSION: both models display acceptable ability to predict mortality. An important advantage is that they are easy to apply in daily practise and thus are helpful for individual decision-making regarding diagnostic/therapeutic interventions and advance care planning.

Risk factors of mortality in older patients with dementia in psychiatric care.

OBJECTIVE: To examine the mortality risk, and its risk factors, of older patients with dementia in psychiatric care. METHODS: We constructed a cohort of dementia patients through data linkage of four Dutch registers: the Psychiatric Case Register Middle Netherlands (PCR-MN), the hospital discharge register, the population register, and the national cause of death register. All dementia patients in PCR-MN aged between 60 and 100 years between 1 January 2000 and 31 December 2010 were included. Risk factors of mortality were investigated using Cox proportional hazard regression models with adjustment for age, sex, setting of care, nationality, marital status, dementia type, and psychiatric and somatic comorbidities. RESULTS: In total, 4297 patients were included with a median age of 80 years. The 1-year, 3-year, and 5-year mortality were 16.4%, 44.4%, and 63.5%, respectively. Determinants that increased the 1-year mortality were: male sex (adjusted hazard ratio [HR]: 1.49; 95% confidence interval [95% CI], 1.26-1.76), higher age (HR 1.08; 95% CI, 1.07-1.09), inpatient psychiatric care (HR 1.52; 95% CI, 1.19-1.93), more somatic comorbidities (HR 1.67; 95% CI, 1.49-1.87), and cardiovascular disease separately (HR 1.54; 95% CI, 1.30-1.82). Results for 3-year and 5-year mortality were comparable. Living together/married increased the 3- and 5-year mortality, and Dutch nationality increased the 5-year mortality. There were no differences in mortality with different types of psychiatric comorbidity. CONCLUSION: Mortality of dementia patients in psychiatric care was high, much higher than mortality in the general older population. The results of this study should raise awareness about their unfavourable prognosis, particularly older patients, men, inpatients, and patients with more somatic comorbidity.

Risk factors for in-hospital mortality in patients with dementia.

OBJECTIVE: To examine the in-hospital mortality rate, and its risk factors, for patients with dementia admitted to hospital. STUDY DESIGN: We constructed an observational cohort study through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register (PR) and the national cause of death register. Patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010 were included. MAIN OUTCOME MEASURES: Risk factors for in-hospital mortality were investigated using multivariable Cox proportional hazard regression models that included sex, age, marital status, ethnicity, somatic comorbidity, type of dementia and urgency of admission. RESULTS: 40,500 patients were included in the cohort. The overall in-hospital mortality rate was 11.1%. Factors that significantly increased the mortality risk were: male sex (adjusted hazard ratio (HR) 1.52, 95%-confidence interval (95%-CI) 1.43-1.63), higher age (adjusted HR 1.03, 95%-CI 1.03-1.04), living with a partner (adjusted HR 1.39, 95%-CI 1.30-1.49), acute admission (adjusted HR 2.16, 95%-CI 1.97-2.36) and Alzheimer's disease (adjusted HR 1.21, 95%-CI 1.13-1.29). Cardiovascular disease was the most common cause of in-hospital mortality. CONCLUSIONS: This nationwide study found several independent risk factors for the in-hospital mortality of patients with dementia, including male sex, higher age, living with a partner, acute admission, and Alzheimer's disease. These risk factors should be taken into account by clinicians and caregivers as they will indicate whether patients are at risk of a more unfavourable outcome during hospital admission.