Neural Functioning in Late-Life Depression: An Activation Likelihood Estimation Meta-Analysis.

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico-limbic-striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico-striatal-cerebellar network in the neurophysiopathology of LLD.

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth.

Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Comparison of Computerized Prescription Support Systems in COVID-19 Patients: INTERCheck and Drug-PIN.

The coronavirus disease 19 (COVID-19) infection requires major efforts in healthcare systems, due to the high risk of mortality, particularly in subjects with significant comorbidity (≥ 2 pathologies) and polypharmacy (≥ 5 drugs). The treatment of COVID-19 needs a careful evaluation, to reduce the risk of potentially adverse drug reactions. The aim of the study was to examine the use of computerized prescription support in the management and treatment of the COVID-19 infection. We evaluated n.33 patients (51% females) admitted to the west COVID Low-Medium Intensity of Care of Sant'Andrea Hospital during the period March-April 2020 and n.42 subjects (50% females) admitted to the Internal Medicine ward (as control group), by INTERCheck® and Drug-PIN®. The comorbidity (n. pathologies), polypharmacy (n. drugs), and total INTERCheck score in COVID-19 patients and controls were, respectively (mean ± standard deviation): 5.8 ± 3.8, 7.9 ± 4.5, and 9.2 ± 7.1 and 6.8 ± 2.6, 8.0 ± 2.6, and 4.9 ± 3.8 (statistically significant for comorbidity p < 0.01 and INTERCheck score p < 0.01). The correlation between the scores obtained by the INTERCheck and Drug-PIN software was statistically significant, either at admission (p < 0.0000001) or during hospitalization (p < 0.00000001). Both the computerized prescription support systems, INTERCheck® and Drug-PIN®, are useful to better characterize the patients and to ameliorate the drugs prescriptions in COVID-19 infection, with particular attention to the elderly population.

Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review.

Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.

Erosion of telomeric 3'-overhangs in white blood cells of aged subjects with high frequency of very short telomeres.

After extended proliferation, cells enter a state of replicative quiescence that is probably due to progressive telomere shortening. It is supposed that changes in telomere structure eventually expose the chromosome ends to undesired recombination events and thus promote cell senescence. The telomeric 3'-overhang is crucial for efficient chromosome capping, but its specific role in telomere shortening and in triggering the senescence program is uncertain. We have addressed this issue by measuring the 3'-overhangs of a human tissue cells aging in vivo. The 3'-overhangs were analyzed in blood samples from 41 individuals aged 91-106 years and 89 individuals ranging from 6 months to 85 years. We found that the overall 3'-overhang length did not significantly change with age, but did, however, find extensively eroded 3'-overhangs in 3 subjects of the 91-106 years cohort and one 61 years old subject affected with Down syndrome. These subjects had 3'-overhang length distributions skewed towards shorter tails, the shortest overall telomere lengths and the highest frequencies of very short telomeres. These data raise the possibility that during ageing very short telomeres with very poor 3'-overhangs can reach a critical point for functional telomeres.

Stress in centenarians.

Everybody is subject to a physical clock, determining the calendar age, and also to a biological clock, the speed of which depends on the interaction between the genetic reserves and the environment. Stress is taken into account more and more as one of the main factors responsible for the acceleration of the biological clock and the dishomogeneity of the aging process. Despite the fact that centenarians are prone to chronic stress due to a progressive loss of self-sufficiency, more than a half of our centenarians were not depressed and had a low trait-anxiety: they showed an emotional tendency to react with a low anxiety-intensity to stressful conditions. Their good physical conditions may be explained by a positive character-disposition and by strong adaptability to the adversities of the life. Personality traits can be reduced to five basic phenomena, the so-called Big Five: extroversion, agreeableness, conscientiousness, openness to experience and emotional stability. In our sample 65.4% were classified as extroverted, 50% as open minded and 34.5% showed good emotional stability. In the centenarians aging of all apparatuses was slowed down by a healthy lifestyle and also by good adaptability that allowed for a positive and effective response to stress throughout their whole lives.

Event related brain potentials in elderly patients with recently diagnosed isolated systolic hypertension.

OBJECTIVE: Isolated Systolic Hypertension (ISH) is a known risk factor for cognitive impairment, but the time of onset of neurocognitive changes relative to the onset of ISH has yet to be established. The purpose of this study was to investigate the relationship between systolic BP values and neurocognitive function in the early stages of ISH. METHODS: Twenty elderly patients with recently (< 2 years) diagnosed ISH and 10 elderly normotensive controls underwent Ambulatory Blood Pressure Monitoring (ABPM) and neurocognitive assessment, performed using the Mini Mental State Examination (MMSE), and the recording of ERPs with an odd ball acoustic paradigm. RESULTS: There were no significant differences in MMSE scores or in the P300 latency between ISH patients and controls. The N2 latency was significantly higher in ISH patients vs. controls (p<0.0001), and showed a significant association with both clinical and ambulatory systolic BP and pulse pressure values in the overall study population. CONCLUSIONS: These findings suggest the existence of early subclinical alterations in neurocognitive function in early ISH, detectable through ERPs. SIGNIFICANCE: Our findings underscore the ISH may constitute a threat to neurocognitive health in the elderly.

Is it possible to predict one-year survival in centenarians? A neural network study.

BACKGROUND: Human life expectancy is constantly increasing: the challenge for modern geriatric medicine is to identify the means to reach successfully extreme longevity. OBJECTIVE: To determine which are the survival determinants in centenarians using a neural network. METHODS: Sample of 110 centenarians living in Rome, mean age 101.6 years (SD=1.8) with a sex ratio males:females of 1:3. We administered an extensive health interview (lasting 1-2 h) to each subject. The questionnaire, carried out according to the Geriatric Multidimensional Assessment, is made up of 100 items including a comprehensive health and psychosocial assessment aimed at various topics of general health and well-being and some scales used in geriatric practice. We applied several three-layered feed-forward neural networks by mixing in different ways the most important of the 100 items. RESULTS: The most predicting powered net is the one constructed with 23 variables regarding comorbidity, cardiovascular risk factors, cognitive status, mood, functional status and social interactions, which therefore are strictly related to survival in centenarians. CONCLUSION: Survival in longevity is a complex biological phenomenon, which is an ideal field for using the neural network as a statistic method. The net shows us that the maintenance of social relationships even in presence of disability is of major importance for survival in the oldest old.

[Risk factors for cognitive impairment]. / Fattori di rischio per il decadimento cognitivo.

Cognitive impairment is an invalidating condition and its prevalence increases significantly with age. It is very important to identify the risk factors for cognitive impairment. Aside from age, sex, familiary history and educational level, the other major risk factors (hypertension, hypercolesterolemia, diabetes mellitus and tobacco), known to be associated frequently with different cerebrovascular diseases, might also contribute to degenerative forms of cognitive impairment because they might favour cerebral microvascular alterations with hypoperfusion, demyelinization and ischemic lesions of subcortical white matter. Longitudinal epidemiological studies detected that arterial hypertension, hypercolesterolemia and tobacco are frequently associated with degenerative forms of cognitive impairment. Some studies show there is no relationship between cognitive impairment and diabetes mellitus, while other underline its role; light alcohol drinking might protect against cognitive impairment. Other recently identified risk factors might be hyperhomocysteinemia and high C-reactive protein blood levels because they seem to be associated with cognitive impairment.

Event-related brain potentials in elderly dippers and nondippers with recently diagnosed hypertension.

Several studies have shown a relationship between blood pressure (BP) and cognitive function. Yet very few studies have addressed circadian BP patterns in this context, perhaps due to poor availability of suitable methods to detect slight changes in the cognitive state. Today, brain event-related potentials (ERPs) allow us to detect subclinical changes in cognitive function. We enrolled 30 elderly patients with recently diagnosed hypertension (<2 years) that had never been treated: 18 dippers and 12 nondippers. Patients underwent 24-h ambulatory blood pressure monitoring (ABPM). Careful assessment of their cognitive state was carried out using the mini mental state examination (MMSE), and the recording of P300 and N2 ERPs. No significant differences between the two groups were found. MMSE scores in dippers and nondippers were similar (29.5+/-0.71 vs. 29.3+/-1.07, respectively; p =0.611), as were P300 latency values (377.78+/-33.28 vs. 364.67+/-35.12 in the central (Cz) position, p =0.310; 379.22+/-32.94 vs. 365.25+/-35.07 in the occipital (Pz) position, p =0.277) and N2 wave latency values (253.83+/-24.9 vs. 249.17+/-24.47 in the Cz position, p =0.617; 251.56+/-25.86 vs. 246.58+/-25.46 in the Pz position, p =0.608). These data show no association between the nondipping pattern and lower cognitive function in elderly subjects with recent hypertension.

[Smoking and survival in centenarians]. / Abitudine al fumo e sopravvivenza nei centenari.

Cigarette smoking has been clearly linked to the most common causes of death in the elderly and contributes to the higher death rate and disability rate associated with many chronic illnesses that are common in this age group. The combination of smoking along with other risk factors like hypertension and diabetes increase high frequency disease, and disability as well as adding to an increase in mortality rate. In order to verify if a healthy lifestyle really favours longevity and how much smoking is incompatible with extreme longevity, we investigated the prevalence of smokers and the total smoking exposure of a sample of centenarians as regards residual survival and health conditions. Our sample consists of 157 centenarians selected among the registered residents of Rome: 39 males and 118 females (ratio = 1:3), mean age being 101.59 years (sd = 1.8). 83.8% of the centenarians have never smoked, 13.5% are former smokers, and 2.7% are active smokers. The average starting age of smoking was 21.2 years while the average age of quitting in former smokers was 65.7 years with an average of 44.7 smoking years (sd = 17.1). The average number of smoked cigarettes per day is quite low, less than 10 cigarettes. There seemed to be a significant difference (p < 0.001) in gender results in smokers: male centenarians were 46%, while female reached only 8.1%. Statistically significant higher prevalence of diseases illnesses were noted among centenarian smokers over the age of 65 (p < 0.02). Moreover Cox's regression has shown in centenarians a lower survival rate (p < 0.05) in smokers than in non-smokers. In conclusion, our study is evidence that smoking is for all, but some exceptional subjects, incompatible with successful aging and compromises life expectancy even in extreme longevity.

[Hypercholesterolemia, cardiovascular risk, and hypocholesteremic treatment in the elderly]. / Ipercolesterolemia, rischio cardiovascolare e terapia ipocolesterolemizzante nell'anziano.

The role of cholesterol as a cardiovascular risk factor in the elderly is not completely clear at the moment. Epidemiologic studies show a continuous relation between cholesterol levels and cardiovascular risk even in the elderly, in fact, in spite of a lower Relative Risk, they have a greater Absolute Risk and Absolute Benefit Increase. In patients over 75-80 years old cholesterol loses its role as a risk factor, probably because of comorbidity, typical in this period. Trials show the efficacy of hypocholesterolemic therapy with statins in secondary prevention in the elderly; fewer data are available for primary prevention. Therapeutic attitudes suggest a pharmacologic intervention of secondary prevention in young and old elderly to lower LDL-C levels, which are more closely related to the events. In primary prevention we should use drugs to reach a LDL-C level lower for each additional risk factor, until 75 years old; in the old elderly we should decide on drug therapy according to the biological age and expected lifespan. Statins seem to be the most effective and safest drugs to reach this aim.