Signs and symptoms method in neuropsychology: A standardized observational examination of cognitive functions can be effective in detecting mild cognitive impairment.

OBJECTIVE: The present study aimed at investigating the sensitivity and specificity of the NeuroPsychological Examination (NPE), a systematic collection of cognitive signs and symptoms based on the observation of the patient's behavior during a clinical interview, in detecting Mild Cognitive Impairment (MCI). METHOD: 475 participants, 208 suffering from MCI, 188 suffering from dementia and 79 subjective cognitive decline (SCD), have been assessed using NPE for the presence of signs and symptoms of cognitive impairment. Receiver operating characteristic (ROC) curve analysis and the Youden's test were used to determine the more appropriate cutoff points for the number of neuropsychological signs at the NPE that enabled to discriminate SCD from MCI, SCD from dementia and MCI from dementia. A sensitivity and specificity analysis and comparisons among the three groups were conducted. RESULTS: The mean number of signs at the NPE were 1.73 for SCD, 7.98 for MCI and 12.82 for dementia. Pairwise comparisons among the three group of participants showed significant differences (SCD vs. MCI, p < .001, r = -0.66; SCD vs. dementia, p < .001, r = -0.76; MCI vs. dementia, p < .001, r = -0.44). The criterion of 3 signs at the NPE showed a sensitivity of 0.95 (95% CI [0.91, 0.97]) and a specificity of 0.76 (95% CI [0.65, 0.84]) in discriminating SCD from MCI participants. CONCLUSIONS: A signs and symptoms approach could be a useful tool for clinical neuropsychologists working in the field of MCI and dementia assessment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diencephalic versus Hippocampal Amnesia in Alzheimer's Disease: The Possible Confabulation-Misidentification Phenotype.

BACKGROUND: Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants. OBJECTIVE: We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype. METHODS: We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test. RESULTS: Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (p < 0.001), temporal disorientation (p < 0.02), misidentification (p = 0.013), other delusions (p = 0.002), and logorrhea (p = 0.004) than the CA-ADs. In addition, more social disinhibition (p = 0.018), reduction of insight (p = 0.029), and hallucination (p = 0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy. CONCLUSION: We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.

Autonomic function predicts cognitive decline in mild cognitive impairment: Evidence from power spectral analysis of heart rate variability in a longitudinal study.

Background: Despite the emerging clinical relevance of heart rate variability (HRV) as a potential biomarker of cognitive decline and as a candidate target for intervention, there is a dearth of research on the prospective relationship between HRV and cognitive change. In particular, no study has addressed this issue in subjects with a diagnosis of cognitive status including cognitive impairment. Objective: To investigate HRV as a predictor of cognitive decline in subjects with normal cognition (NC) or Mild Cognitive Impairment (MCI). Specifically, we tested the literature-based hypothesis that the HRV response to different physical challenges would predict decline in different cognitive domains. Methods: This longitudinal study represents the approximately 3-year follow-up of a previous cross-sectional study enrolling 80 older outpatients (aged ≥ 65). At baseline, power spectral analysis of HRV was performed on five-minute electrocardiographic recordings at rest and during a sympathetic (active standing) and a parasympathetic (paced breathing) challenge. We focused on normalized HRV measures [normalized low frequency power (LFn) and the low frequency to high frequency power ratio (LF/HF)] and on their dynamic response from rest to challenge (Δ HRV). Extensive neuropsychological testing was used to diagnose cognitive status at baseline and to evaluate cognitive change over the follow-up via annualized changes in cognitive Z-scores. The association between Δ HRV and cognitive change was explored by means of linear regression, unadjusted and adjusted for potential confounders. Results: In subjects diagnosed with MCI at baseline a greater response to a sympathetic challenge predicted a greater decline in episodic memory [adjusted model: Δ LFn, standardized regression coefficient (ß) = -0.528, p = 0.019; Δ LF/HF, ß = -0.643, p = 0.001] whereas a greater response to a parasympathetic challenge predicted a lesser decline in executive functioning (adjusted model: Δ LFn, ß = -0.716, p < 0.001; Δ LF/HF, ß = -0.935, p < 0.001). Conclusion: Our findings provide novel insight into the link between HRV and cognition in MCI. They contribute to a better understanding of the heart-brain connection, but will require replication in larger cohorts.

Crystal Ball Health Policies: A Case Against Preventive Testing For Alzheimer's Disease.

After the recent approval of a new drug for the treatment of Alzheimer's disease, the first in almost twenty years, it is useful to consider what are the real possibilities to make a preclinical diagnosis of dementia and to treat its symptoms. The scientific community widely agrees that the drugs available today can only slow down the progression of the disease; it, therefore, seems helpful to warn against encouraging the spread of preventive testing. In fact, faced with the prospect of drugs that promise to act in the first stage of Alzheimer's, there might be an incentive to invest in the research on biomarkers and even healthy adults could be encouraged to increasingly resort to such prediction tests. Our claim, however, is that such massive use of biomarkers would eventually make things worse for many individuals and for society as well. A few examples are given to illustrate this risk. Therefore, our proposal is to limit access to prediction testing until truly effective treatments for Alzheimer's are available.

The "One Health" approach in the face of Covid-19: how radical should it be?

BACKGROUND: The 2020-2021 coronavirus (Covid-19) pandemic is just the latest epidemic event that requires us to rethink and change our understanding of health. Health should no longer be conceived only in relation to human beings, but in unitary terms, as a dimension that connects humans, animals, plants, and the environment (holistic view, One Health). In general, alterations occurring in this articulated chain of life trigger a domino effect. METHODOLOGY: In this paper, we review the One Health paradigm in the light of the Covid-19 pandemic and distinguish two approaches within it that might be dubbed the Prudent one and the Radical one. Each approach is structured in three levels - epistemological, medical, and ethical. RESULTS: In this way, we show how we humans can better address the pandemic today and how, in the future, we can treat the whole living system better, by renouncing our anthropocentric perspective on health. CONCLUSION: We hold that the Prudent approach can be very helpful, and we discuss the medical and ethical issues related to it. We also consider the Radical view and the epistemological turn it requires compared to the Prudent one.

Socially desirable responding in geriatric outpatients with and without mild cognitive impairment and its association with the assessment of self-reported mental health.

BACKGROUND: Socially desirable responding is a potentially relevant issue in older adults and can be evaluated with the Marlowe-Crowne Social Desirability Scale (MCSDS). However, the eight-item MCSDS has never been specifically administered to geriatric subjects, and there is a dearth of literature on the relationship between social desirability and cognitive impairment. Also, the connection between social desirability and subjective measures of psychological well-being is a matter of controversy. This study has three main aims. First, to determine the psychometric properties of the eight-item MCSDS in geriatric outpatients without dementia (i.e. with normal cognition (NC) or mild cognitive impairment (MCI)). Second, to investigate the link between social desirability and cognitive functioning. Third, to determine the association between social desirability and the assessment of self-reported mental health. METHODS: Community-dwelling outpatients (aged ≥ 65) were consecutively recruited and neuropsychologically tested to diagnose NC or MCI (n = 299). Social desirability was assessed with the eight-item MCSDS. Depressive and anxiety symptoms were measured with the short Geriatric Depression (GDS-s) and the State-Trait Personality Inventory Trait Anxiety (STPI-TA) scales. RESULTS: On principal components analysis, the eight-item MCSDS was found to have a multidimensional structure. Of the initial three-component solution, only two subscales had acceptable internal consistency (Cronbach's alpha > 0.6): "Acceptance of responsibility" and "Integrity". The third subscale ("Kindness towards others") appeared to gauge two distinct constructs of formal (i.e. politeness) versus substantive (i.e. forgiveness) compassion. On binary logistic regression, only higher income was a significant predictor of formal compassion. Test-retest reliability was substantial to excellent (Gwet's AC2 ≥ 0.8). There were no meaningful differences in social desirability between the NC and MCI groups. Likewise, negative Spearman's correlations between social desirability and cognitive Z-scores across the whole sample were weak (rs < |0.3|) and confined to one MCSDS item. Although social desirability was an independent predictor of the STPI-TA score in multiple linear regression, it explained only a marginal amount of incremental variance in anxiety symptoms (less than 2%). CONCLUSIONS: Our results suggest that social desirability need not be a major concern when using questionnaires to assess mental health in geriatric outpatients without dementia.

What Should We Do With People Who Cannot or Do Not Want to Be Protected From Neurotechnological Threats?

Neurotechnologies can pose a threat to people's privacy and mental integrity. Hence the proposal of establishing neurorights (Ienca and Andorno, 2017) and technical principles for the implementation of these rights (Lavazza, 2018). However, concepts such as "the extended mind" and what might be called "the post-human objection" can be said to challenge this protection paradigm. On the one hand, it may be difficult to outline the cognitive boundaries between humans and machines (with the consequent ethical and legal implications). On the other hand, those who wish to make strong use of neurotechnologies, or even hybridize with them, reject the idea that privacy and mental integrity should be protected. However, from the latter view, issues may arise relating to the protection of persons entering into relationships with posthumanist people. This article will discuss these scenarios as well as the ethical, legal, social, and political issues that could follow from them.

Signs and symptoms method in neuropsychology: A preliminary investigation of a standardized clinical interview for assessment of cognitive decline in dementia.

Psychologists usually perform a preliminary assessment of the person's cognitive status through a brief interview conducted before the formal testing. However, this exam has not yet been standardized with ad hoc recommendations in psychology literature. In this work, a standard observational NeuroPsychological Examination (NPE) designed for psychologists was proposed, and its clinical effectiveness evaluated. The NPE was administered to patients referred to a neuropsychological service in a memory clinic over a 2-year period. The NPEs of the patients with Alzheimer dementia (AD), vascular dementia (VaD), and healthy controls (HC) were retrospectively retrieved. Comparisons among the three groups were conducted. Abnormalities/signs identified during the NPE in the AD and VaD groups are more numerous compared to those reported in the HC group. About 80% of HCs show none or only one abnormal sign. Vice versa, 87.5% of both AD and VaD patients show three or more abnormalities. Accordingly, the NPE has 0.88 (95%CI = 0.81-0.95) sensitivity and 0.95 (95%CI = 0.88-1.02) specificity for detecting cognitive decline when a cut-point of three or more signs is applied. Some significant differences also emerge on the number of pathological signs between AD and VaD patients. NPE is a promising tool with demonstrated diagnostic utility in dementia patients.

Different dimensions of social support differentially predict psychological well-being in late life: opposite effects of perceived emotional support and marital status on symptoms of anxiety and of depression in older outpatients in Italy.

BACKGROUND: Social support is important to psychological well-being in late life. However, findings in the literature regarding its effects are mixed, less information is available for anxiety than for depressive symptoms, and few studies have been carried out in Italy. Therefore, the aim of this study was to investigate the influence of social support on symptoms of anxiety and of depression in a sample of geriatric outpatients in Italy. METHODS: This cross-sectional study consecutively enrolled 299 outpatients without dementia (age ≥ 65, all neuropsychologically tested). Social support was assessed with the ENRICHD Social Support Instrument and by interview. Symptoms of anxiety and of depression were evaluated with short versions of the State-Trait Personality Inventory Trait Anxiety and Geriatric Depression scales. The relationship between social support and psychological well-being was examined by multiple linear regression models with socio-demographic and clinical variables, including cognitive performance, as potential confounders. RESULTS: Perceived emotional support was a negative predictor of symptoms of anxiety (standardised beta coefficient (ß) -0.288, standard error (SE) 0.074, P < 0.001) and symptoms of depression (ß -0.196, SE 0.040, P < 0.001). On the contrary, marital status (i.e. being married) was a positive predictor of symptoms of anxiety (ß 0.199, SE 0.728, P = 0.003) and symptoms of depression (ß 0.142, SE 0.384, P = 0.035). CONCLUSIONS: Different dimensions of social support differentially affect psychological well-being. The protective effect of perceived emotional support is consistent with social cognitive models of health. The harmful effect of being married may be capturing the distress of the pre-bereavement period. Alternatively, it may reflect oppression by gender roles within marriage in a predominantly female sample in a traditional society. Our findings provide insight into the relationship between social support and psychological well-being, and identify potential targets for psychosocial interventions promoting mental health in late life.

Autonomic function in amnestic and non-amnestic mild cognitive impairment: spectral heart rate variability analysis provides evidence for a brain-heart axis.

Mild cognitive impairment (MCI) is a heterogeneous syndrome with two main clinical subtypes, amnestic (aMCI) and non-amnestic (naMCI). The analysis of heart rate variability (HRV) is a tool to assess autonomic function. Cognitive and autonomic processes are linked via the central autonomic network. Autonomic dysfunction entails several adverse outcomes. However, very few studies have investigated autonomic function in MCI and none have considered MCI subtypes or the relationship of HRV indices with different cognitive domains and structural brain damage. We assessed autonomic function during an active orthostatic challenge in 253 oupatients aged ≥ 65, [n = 82 aMCI, n = 93 naMCI, n = 78 cognitively normal (CN), neuropsychologically tested] with power spectral analysis of HRV. We used visual rating scales to grade cerebrovascular burden and hippocampal/insular atrophy (HA/IA) on neuroimaging. Only aMCI showed a blunted response to orthostasis. Postural changes in normalised low frequency (LF) power and in the LF to high frequency ratio correlated with a memory test (positively) and HA/IA (negatively) in aMCI, and with attention/executive function tests (negatively) and cerebrovascular burden (positively) in naMCI. These results substantiate the view that the ANS is differentially impaired in aMCI and naMCI, consistently with the neuroanatomic substrate of Alzheimer's and small-vessel subcortical ischaemic disease.

Does the Right Focal Variant of Alzheimer's Disease Really Exist? A Literature Analysis.

BACKGROUND: Alzheimer's disease (AD) is a clinically heterogeneous disease. Multiple atypical syndromes, distinct from the usual amnesic phenotype, have been described. In this context, the existence of a right variant of AD (RAD), characterized by enduring visuospatial impairment associated with right-sided asymmetric brain damage, has been proposed. However, to date, this phenotype remains controversial. In particular, its peculiar characteristics and the independence from more prevalent cases (especially the posterior cortical atrophy syndrome) have to be demonstrated. OBJECTIVE: To explore the existence of focal RAD on the basis of existing literature. METHODS: We performed a literature search for the description of atypical AD presentations, potentially evoking cases of focal RAD. To be considered as affected by RAD, the described cases had to present: 1) well documented right-sided asymmetry at neuroimaging; 2) predominant cognitive deficits localizable on the right hemisphere; 3) no specific diagnosis of a known variant of AD. RESULTS: Twenty-one cases were found in the literature, but some of them were subsequently excluded because some features of a different clinical syndrome were overlapped with the clinical features of RAD. Thirteen positive cases, three of them with pathologically confirmed AD, remained. A common right clinical-radiological syndrome, characterized by memory and visuospatial impairment with temporal and parietal involvement, consistently emerged. However, the heterogeneity among the reports prevented a definitive and univocal description of the syndrome. CONCLUSION: Even if sporadic observations strongly support the existence of a focal RAD, no definitive conclusions can still be drawn about it as an independent condition.

Validation study of the Italian version of Communication Activities of the Daily Living (CADL 2) as an ecologic cognitive assessment measure in older subjects.

INTRODUCTION: Communication can be affected by age related cognitive decline and mental deterioration. The second edition of the Communication Activities of the Daily Living (CADL 2) appears as an interesting ecological assessment tool of cognitive functions in old age. OBJECTIVE: The aim of this work is to (1) develop an Italian version of CADL 2, (2) to test its psychometric properties in terms of reliability and validity, and (3) to measure CADL 2 discriminative capacity between cognitively healthy and cognitively impaired older subjects. METHOD: One hundred and eleven subjects were enrolled (36 M; 75 F, age 80, 80.85 ± 7 years, education 9.3 ± 4.7 years). The CADL 2 was administered together with a standard neuropsychological battery. RESULTS: The CADL 2 showed good reliability and correlates with all the cognitive evaluation tests. The CADL 2's area under the curve was equal to 0.80, index of good diagnostic accuracy. CONCLUSIONS: The CADL 2 is an appropriate assessment tool for communication skills in aging.

Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial.

STUDY OBJECTIVE: To assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial. DESIGN: Randomized controlled pilot trial. SETTING: Perioperative care in a tertiary care teaching hospital with outpatient follow-up. PATIENTS: One hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls. INTERVENTIONS: Randomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists. MEASUREMENTS: An experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes. MAIN RESULTS: The Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ±â€¯25% vs. 49 ±â€¯28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%). CONCLUSIONS: Intraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery. A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD. TRIAL REGISTRATION NUMBER: NCT02428062www.clinicaltrials.gov.

Alzheimer's Disease Diagnosis: Discrepancy between Clinical, Neuroimaging, and Cerebrospinal Fluid Biomarkers Criteria in an Italian Cohort of Geriatric Outpatients: A Retrospective Cross-sectional Study.

BACKGROUND: The role of cerebrospinal fluid (CSF) biomarkers, and neuroimaging in the diagnostic process of Alzheimer's disease (AD) is not clear, in particular in the older patients. OBJECTIVE: The aim of this study was to compare the clinical diagnosis of AD with CSF biomarkers and with cerebrovascular damage at neuroimaging in a cohort of geriatric patients. METHODS: Retrospective analysis of medical records of ≥65-year-old patients with cognitive impairment referred to an Italian geriatric outpatient clinic, for whom the CSF concentration of amyloid-ß (Aß), total Tau (Tau), and phosphorylated Tau (p-Tau) was available. Clinical diagnosis (no dementia, possible and probable AD) was based on the following two sets of criteria: (1) the Diagnostic Statistical Manual of Mental Disorders (DSM-IV) plus the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and (2) the National Institute on Aging-Alzheimer's Association (NIA-AA). The Fazekas visual scale was applied when a magnetic resonance imaging scan was available. RESULTS: We included 94 patients, mean age 77.7 years, mean Mini Mental State Examination score 23.9. The concordance (kappa coefficient) between the two sets of clinical criteria was 70%. The mean CSF concentration (pg/ml) (±SD) of biomarkers was as follows: Aß 687 (±318), Tau 492 (±515), and p-Tau 63 (±56). There was a trend for lower Aß and higher Tau levels from the no dementia to the probable AD group. The percentage of abnormal liquor according to the local cutoffs was still 15 and 21% in patients without AD based on the DSM-IV plus NINCDS-ADRDA or the NIA-AA criteria, respectively. The exclusion of patient in whom normotensive hydrocephalus was suspected did not change these findings. A total of 80% of patients had the neuroimaging report describing chronic cerebrovascular damage, while the Fazekas scale was positive in 45% of patients overall, in 1/2 of no dementia or possible AD patients, and in about 1/3 of probable AD patients, with no difference across ages. CONCLUSION: We confirmed the expected discrepancy between different approaches to the diagnosis of AD in a geriatric cohort of patients with cognitive impairment. Further research is needed to understand how to interpret this discrepancy and provide clinicians with practical guidelines.