Graph analysis uncovers an opposing impact of methylphenidate on connectivity patterns within default mode network sub-divisions.

BACKGROUND: The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate (MPH) administration has been shown before to modulate impulsive behavior, though it is not yet clear whether these effects relate to MPH-induced changes in DMN connectivity. To address this gap, we assessed the impact of MPH administration on functional connectivity patterns within and between distinct DMN sub-networks and tested putative relations to variability in sub-scales of impulsivity. METHODS: Fifty-five right-handed healthy adults underwent two resting-state functional MRI (rs-fMRI) scans, following acute administration of either MPH (20 mg) or placebo, via a randomized double-blind placebo-controlled design. Graph modularity analysis was implemented to fractionate the DMN into distinct sub-networks based on the impact of MPH (vs. placebo) on DMN connectivity patterns with other neural networks. RESULTS: MPH administration led to an overall decreased DMN connectivity, particularly with the auditory, cinguloopercular, and somatomotor networks, and increased connectivity with the parietomedial network. Graph analysis revealed that the DMN could be fractionated into two distinct sub-networks, with one exhibiting MPH-induced increased connectivity and the other decreased connectivity. Decreased connectivity of the DMN sub-network with the cinguloopercular network following MPH administration was associated with elevated impulsivity and non-planning impulsiveness. CONCLUSION: Current findings highlight the intricate effects of MPH administration on DMN rs-fMRI connectivity, uncovering its opposing impact on distinct DMN sub-divisions. MPH-induced dynamics in DMN connectivity patterns with other neural networks may account for some of the effects of MPH administration on impulsive behavior.

The Two-Track Model of Dementia Grief and spousal response to illness and death.

This cross-sectional study examined the experiences of healthy spouses caring for their partners via the Two-Track Model of Dementia Grief thereby broadening our understanding of the functional and relational aspects of this process. The 122 participating older adults had spouses drawn from four groups: mild to moderate cognitive-impairment; advanced cognitive-impairment; deceased following dementia; and, healthy controls. They completed a battery of self-report measures. Results showed elevated scores on both tracks of the model for all affected groups. Assisting spouses of those living with cognitive-impairment begins with the earliest symptoms of decline and continues after the death of the loved one.

Cognitive dysfunction following COVID-19 infection.

The coronavirus (COVID-19) pandemic is still evolving, causing hundreds of millions of infections around the world. The long-term sequelae of COVID-19 and neurologic syndromes post COVID remain poorly understood. The present study aims to characterize cognitive performance in patients experiencing cognitive symptoms post-COVID infection. Patients evaluated at a post COVID clinic in Northern Israel who endorsed cognitive symptoms were referred for neurologic consultation. The neurologic work-up included detailed medical history, symptom inventory, neurological examination, the Montreal Cognitive Assessment (MoCA), laboratory tests and brain CT or MRI. Between December 2020 and June 2021, 46 patients were referred for neurological consultation (65% female), mean age 49.5 (19-72 years). On the MoCA test, executive functions, particularly phonemic fluency, and attention, were impaired. In contrast, the total MoCA score, and memory and orientation subscores did not differ from expected ranges. Disease severity, premorbid condition, pulmonary function tests and hypoxia did not contribute to cognitive performance. Cognitive decline may affect otherwise healthy patients post-COVID, independent of disease severity. Our examination identified abnormalities in executive function, attention, and phonemic fluency. These findings occurred despite normal laboratory tests and imaging findings.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Spousal Mourning for Partners Living with Cognitive Impairment: The Interplay of Attachment and the Two-Track Model of Dementia Grief.

The aim of the present research was to study the interplay of Attachment Theory and the Two-Track Model of Dementia Grief. To examine the research hypotheses, a cross-sectional study was designed and included 122 participants (Mean age = 72.77) drawn from four groups: spouses of people living with mild to moderate cognitive impairment, spouses of people living with advanced cognitive impairment, widowed spouses of deceased dementia patients, and a control group. Participants completed a battery of self-report questionnaires. Results showed that secure attachment constitutes a significant protective factor with regard to bio-psycho-social symptomatology (Track I) as well as difficulties in the relational bond with the spouse and grief over their deterioration (Track II). The results of the research support integrating attachment-based insights into clinical work with spouses coping with the losses accompanying cognitive decline and the grief processes that are operant in these losses.

The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters.

INTRODUCTION: One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. METHODS: A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. RESULTS: Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25-75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). CONCLUSIONS: One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. IMPLICATIONS: One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

Cannabis-related cognitive impairment: a prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study.

OBJECTIVES: In patients with cancer, the use of medical cannabis has increased significantly during the recent years. There is evidence that cannabis consumption may affect cognitive performance; however, this potential effect has not been investigated prospectively in patients with cancer to date. We aimed to evaluate the effect of cannabis consumption on cognitive abilities as well as on symptom relief in patients with cancer during chemotherapy treatment. PATIENTS AND METHODS: A prospective study was carried out on a group of 17 patients on cannabis treatment (case) who were compared with 17 patients not on cannabis treatment (control). Participants completed self-reported questionnaires (the Hospital Anxiety and Depression Scale, Brief Fatigue Inventory, European Organization of Research and Treatment of Cancer core questions on the Quality of Life Questionnaire) and underwent the following neurocognitive tests: Montreal Cognitive Assessment, Digit Symbol Substitution subtest (WAIS III) and Digital-Finger Tapping Test. The evaluation was conducted before the initiation of cannabis consumption and 3 months later during the period of cannabis use. RESULTS: Improvement in executive functioning was demonstrated in the case group. In aspects of symptoms, improvement in fatigue, appetite and sleep disorder was demonstrated after cannabis consumption. Patients consuming cannabis did not differ from the control group in cognitive functioning over 3 months of use. No significant cognitive decline was observed in either group over time. CONCLUSION: These preliminary findings suggest that the short-term use of cannabis during chemotherapy treatment improved disease-related symptoms and did not affect cognitive skills in patients with cancer.

[ADHD IN THE AGING POPULATION: A NEW DIFFERENTIAL DIAGNOSIS?]

INTRODUCTION: During midlife and aging, subjective reports regarding cognitive decline increase in frequency. Age-associated cognitive impairment, mild cognitive impairment and dementia, increase in prevalence and are frequently diagnosed. Background medical conditions and risk factors are often regarded as contributing to the cognitive decline. The contribution of prior undiagnosed ADHD (Attention Deficit Hyperactive Disorder) is seldom considered. The aim of the current study was to examine whether childhood or adult ADHD should be considered relevant in the differential diagnosis of cognitive complaints during midlife and aging. METHODS: Thirty-six subjects, aged 50-70 years, diagnosed with probable ADHD (pADHD) and 29 controls participated in the present study. The pADHD group included 12 individuals self-referred due to self-complaints regarding cognitive decline or memory impairment, previously undiagnosed with ADHD (ADHD-A) but with lifelong symptomatology of ADHD and fulfilling ADHD criteria and 24 individuals, parents of diagnosed ADHD children and reporting ADHD symptoms (ADHD-B) , without complaints regarding recent cognitive decline. The neuropsychological evaluation included the Conners' Adult ADHD Rating Scale-SL, Beck Depression Inventory, and the following cognitive tests: logical memory subscale (LM- WMS), California Verbal study was conducted at the Cognitive Neurology Clinic - Rambam Health Care Campus and was granted the approval of the local IRB committee. RESULTS: ADHD-A were impaired on attention parameters while memory and executive functions were intact. ADHD-B did not present measurable attention or other neuropsychological deficits as compared to the control group. Neither group fulfilled criteria for MCI or dementia. CONCLUSIONS: ADHD should be considered as a new/additional entity in the differential diagnosis of subjective cognitive complaints among middle-aged and older persons. The recognition of the specific cognitive and behavioral profiles of ADHD should contribute to the ability to reach optimal differentiation from pre-dementia conditions in order to tailor appropriate therapies. The pathophysiology and future trajectory of the emerging ADHD symptomatology in older patients fulfilling lifelong ADHD symptomatology remains to be clarified. When examining older adults, ADHD should be considered as a differential diagnosis.

Cognitive impairment in hodgkin lymphoma survivors.

Cancer-related cognitive impairment (CRCI) is commonly reported post-chemotherapy in adults with solid tumours. Hodgkin lymphoma (HL) mostly affects young adults. Data regarding CRCI in HL survivors (HLS) are scarce. The current study aimed to objectively assess CRCI incidence and characteristics in HLS. HLS, who completed first-line (chemotherapy ± radiation) therapy and remained in complete remission for 6 months to 5 years from therapy end, were evaluated. Age- and education-matched healthy individuals served as controls (n = 14). Test results were compared to population norms and healthy controls. Study participants completed self-reported questionnaires evaluating fatigue, depression, anxiety, quality of life and cognitive function. Subjects underwent neurocognitive evaluation, assessing processing speed, memory, attention, executive functions and intelligence domains. The present study included 51 HLS with a median age of 28 years, mean education of 14·5 ± 2·5 years. Complaints related to cognitive deterioration and fatigue were significantly more severe and frequent in HLS compared to healthy controls. Objective neurocognitive evaluation demonstrated that 30% of HLS were impaired in ≥2 cognitive domains. In conclusion, the present study demonstrates that fatigue and cognitive impairment, predominantly in executive functions and memory, constitute frequent and alarming findings in HLS. These adverse effects can persist and exert an impact on all aspects of life.

Memory, Decision-Making, and the Ventromedial Prefrontal Cortex (vmPFC): The Roles of Subcallosal and Posterior Orbitofrontal Cortices in Monitoring and Control Processes.

The ventromedial prefrontal cortex (vmPFC) prominently and separately features in neurobiological models of decision-making (e.g., value-encoding) and of memory (e.g., automatic veracity-monitoring). Recent decision-making models propose value judgments that inherently comprise of second-order confidence estimates. These demonstrate quadratic relationships with first-order judgments and are automatically encoded in vmPFC activity. Memory studies use Quantity-Accuracy Profiles to capture similar first-order and second-order meta-mnemonic processes, suggesting convergence across domains. Patients with PFC damage answered general knowledge questionnaires under 2 conditions. During forced report, they chose an answer and rated the probability of it being correct (first-order "monitoring"). During free report, they could choose to volunteer or withhold their previous answers (second-order "control") to maximize performance. We found quadratic relationships between first-order and second-order meta-mnemonic processes; voxel-based lesion-symptom mapping demonstrated that vmPFC damage diminished that relationship. Furthermore, damage to subcallosal vmPFC was specifically associated with impaired monitoring and additional damage to posterior orbitofrontal cortex led to deficient control. In decision-making, these regions typically support valuation and choice, respectively. Persistent spontaneous confabulation (false memory production) confirmed the clinical relevance of these dissociations. Compared with patients with no confabulation history, patients who currently confabulate were impaired on both monitoring and control, whereas former confabulators demonstrated impaired monitoring but intact control.

Hypercoagulability, parkinsonism, and Gaucher disease.

Gaucher disease (GD) is a lysosomal disorder caused by inherited deficiency of glucocerebrosidase (GCase), resulting in the accumulation of glucocerebroside in macrophages, termed "Gaucher cells," leading to multiorgan involvement, with hepatosplenomegaly, cytopenias, pulmonary hypertension, and skeletal complications. Various mutations, encoding the GCase gene, cause acute or chronic neuronopathic forms of the disease. The hallmark of GD is the macrophages infiltrating organs, bone marrow, and nervous system compromising their function by inflammation, infarcts, fibrosis, and neuronal damage. Coagulation abnormalities are frequent among GD patients due to reduced production and chronic consumption of coagulation factors. Splenic and bone infarcts often occur in GD patients, but hypercoagulability is not frequent. Detection of thrombophilic risk factors in GD patients may predict a more severe course of the disease. Clinical and genetic studies revealed an association between reduced GCase activity in carriers of GD mutations and GD patients and occurrence of Parkinson disease (PD) and showed that GCase gene mutations are risk factors for PD development. The mechanisms underlying the association of PD and GD are not yet elucidated and should be further explored, particularly the potential involvement of inflammation and coagulation in the neurovascular unit.

Personality type as a predictor for depressive symptoms and reduction in quality of life among stroke survivals.

OBJECTIVE: Although poststroke depression (PSD) and reduction in quality of life (QOL) are prevalent among stroke patients, little is known about the contribution of personality traits to such impairments. This study examines whether particular personality traits predict PSD symptoms (PSDS) and reduction in QOL among stroke survivals using Cloninger's biopsychosocial personality model. We hypothesized that harm avoidance (HA), expressing the tendency to respond intensely to adverse stimuli, characterizes stroke survivors at risk for PSDS and reduction in QOL. METHODS: Hospitalized stroke patients (N = 84, age 63.5 ± 9.7 years) prospectively completed Cloninger's Tridimensional Personality Questionnaire, defining HA dominancy by scoring the three personality dimensions: reward dependence, novelty seeking, and HA. The level of neurologic deficit was evaluated by the National Institutes of Health Stroke Scale. At the 3-month follow-up visit, depressive symptoms and QOL scores were assessed using the Beck Depression Inventory and the Stroke Specific Quality of Life questionnaire. RESULTS: Regression analyses revealed that higher HA scores independently predicted PSDS and reduction in QOL. After controlling for the relative contribution of stroke type and health-related variables, HA and neurologic deficit were significant risk factors for poststroke negative outcomes. CONCLUSION: Our findings emphasize the relevance of Cloninger's theory (manifested by individual HA behavior) as a distinctive means to identifying patients at risk for PSDS and lower QOL after stroke. The role of specific psychological and neurologic aspects involved in the mechanism of PSD should be further explored using biopsychosocial models.

Risk, Resilience, and the Two-Track Model of Dementia Grief Among Spouses of People Living With Cognitive Decline.

Pre-death grief in the context of dementia caregiving is a significant risk factor for depression, burden, anxiety, and adjustment difficulties. The Two-Track Model of Dementia Grief (TTM-DG) provides a bifocal perspective addressing the nature of the emotional attachment to a loved one living with cognitive impairment, along with a medico-psychiatric perspective associated with stress, trauma, and change in life. The aims of the present study were to empirically validate the components of the model as to identify salutary and risk factors for maladaptive grief responses. Participants were 62 spouses of people living with cognitive impairment, and a control group of 32 spouses. All completed a battery of self-report questionnaires. Structural Equation Modeling yielded six variables consistent with the TTM-DG: partner's behavioral disorders; caregiver's burden; social support; physical health; attachment anxiety; and dementia grief as an outcome measure. Additional findings addressed participants at risk for grief difficulties. The findings provide empirical support for the utility of the TTM-DG in the identification of risk factors associated with maladaptive responses and pre-death grief following a spousal cognitive decline. The TTM-DG can assist in the formulation of evidence-based evaluations and interventions to assist spouses caring for their loved ones living with dementia.

Sensitivity to fairness and intentions of others in the ultimatum game in patients with ventromedial prefontal lesions.

This study aimed to examine the relationship between perspective-taking and impaired decision-making in patients with ventromedial prefrontal (VM) lesions, using the Ultimatum Game (UG). In the UG, two players split a sum of money and one player proposes a division while the other can accept or reject this. Eight patients with VM damage and 18 healthy controls participated as responders in a modified version of the UG, in which identical offers can generate different rejection rates depending on the other offers available to the proposer. Participants had to either accept or reject offers of 2:8 NIS (2NIS for them and 8 NIS for the proposer), which were paired with one of four different possible offers (5:5, 4:6, 2:8, 8:2). Results indicate that the controls more often rejected offers of 2:8 when the alternative was 4:6 (a greedy alternative) than when the alternative was 5:5 (fair alternative), whereas the VM patients showed the opposite pattern of decision-making. Additionally, the overall rejection rates were higher in patients as compared to controls. Furthermore, scores on a perspective-taking scale were negatively correlated with rejection rates in the patient group, suggesting that perspective-taking deficits may account for impaired decision-making in VM patients.

Expectations, experiences, and tensions in the memory clinic: the process of diagnosis disclosure of dementia within a triad.

BACKGROUND: Health communication studies emphasize the importance of addressing the needs and expectations of patients and families with the disclosure of grave medical conditions. However, little attention has focused on their expectations and experiences of the clinical encounters in diagnosis disclosure of dementia. METHODS: In-depth post-encounter interviews with ten patients and 17 companions from two memory clinics in Israel were analyzed using grounded theory. The analysis focused on identifying their expectations, their experiences, and their perceptions of the process and outcomes. RESULTS: Major differences exist between patients' and companions' expectations. Patients' expectations were an expression of the lack of knowledge/understanding of the visit's purpose and of insight into the memory deterioration. Companions had more clear-cut expectations: some desired confirmation of the legitimacy and pertinence of their concerns about their relatives' memory problem, whereas others hoped to allay their concerns. Patients' dissatisfaction stemmed mostly from their perceptions of the process, communication, and outcome. Companions' dissatisfaction stemmed from lack of information or of tailored follow-up processes for implementing recommendations provided by the clinic. CONCLUSIONS: Our findings expose two main issues challenging fulfillment of the different and frequently opposing expectations of patients and companions. The first is a consequence of the multi-participant nature of the encounter and the second relates to the character and severity of the disease itself. The discordance between the expectations of the two participants generates conflicts that interfere with meeting their diverse needs within the encounters - with consequent disappointment. The implications of these issues merit consideration in the planning of dementia management.

Sentence comprehension following moderate closed head injury in adults.

The current study explores sentence comprehension impairments among adults following moderate closed head injury. It was hypothesized that if the factor of syntactic complexity significantly affects sentence comprehension in these patients, it would testify to the existence of syntactic processing deficit along with working-memory problems. Thirty-six adults (18 closed head injury patients and 18 healthy controls matched in age, gender, and IQ) participated in the study. A picture-sentence matching task together with various tests for memory, language, and reading abilities were used to explore whether sentence comprehension impairments exist as a result of a deficit in syntactic processing or of working-memory dysfunction. Results indicate significant impairment in sentence comprehension among adults with closed head injury compared with their non-head-injured peers. Results also reveal that closed head injury patients demonstrate considerable decline in working memory, short-term memory, and semantic knowledge. Analysis of the results shows that memory impairment and syntactic complexity contribute significantly to sentence comprehension difficulties in closed head injury patients. At the same time, the presentation mode (spoken or written language) was found to have no effect on comprehension among adults with closed head injury, and their reading abilities appear to be relatively intact.

Fronto-striatal connectivity patterns account for the impact of methylphenidate on choice impulsivity among healthy adults.

Choice impulsivity depicts a preference towards smaller-sooner rewards over larger-delayed rewards, and is often assessed using a delay discounting (DD) task. Previous research uncovered the prominent role of dopaminergic signaling within fronto-striatal circuits in mediating choice impulsivity. Administration of methylphenidate (MPH), an indirect dopaminergic agonist, was shown to reduce choice impulsivity in animals and pathological populations, although significant inter-individual variability in these effects was reported. Whether MPH impacts choice impulsivity among healthy individuals, and whether variability in the impact of MPH is related to fronto-striatal activation and connectivity patterns, has yet to be assessed. Here, fifty-seven healthy young adults completed the DD task twice during fMRI scans, after acute administration of either MPH (20 mg) or placebo, in a randomized double-blind placebo-controlled design. Acute MPH administration was found to reduce choice impulsivity at the group level, yet substantial variability in this behavioral response was observed. MPH was also found to increase activation in the bilateral putamen and the right caudate, and to enhance functional connectivity between the left putamen and medial prefrontal cortex (mPFC), particularly during non-impulsive choices. Notably, the more putamen-mPFC functional connectivity increased during non-impulsive choices following MPH administration, the less an individual was likely to make impulsive choices. These findings reveal, for the first time in healthy adults, that acute MPH administration is associated with reduced choice impulsivity and increased striatal activation and fronto-striatal connectivity; and furthermore, that the magnitude of MPH-induced change in fronto-striatal connectivity may account for individual differences in the impact of MPH on impulsive behavior.

Familial Early-Onset Alzheimer's Caused by Novel Genetic Variant and APP Duplication: A Cross-Sectional Study.

BACKGROUND: The clinical characteristics of symptomatic and asymptomatic carriers of early- onset autosomal dominant Alzheimer's (EOADAD) due to a yet-undescribed chromosomal rearrangement may add to the available body of knowledge about Alzheimer's disease and may enlighten novel and modifier genes. We report the clinical and genetic characteristics of asymptomatic and symptomatic individuals carrying a novel APP duplication rearrangement. METHODS: Individuals belonging to a seven-generation pedigree with familial cognitive decline or intracerebral hemorrhages were recruited. Participants underwent medical, neurological, and neuropsychological evaluations. The genetic analysis included chromosomal microarray, Karyotype, fluorescence in situ hybridization, and whole genome sequencing. RESULTS: Of 68 individuals, six females presented with dementia, and four males presented with intracerebral hemorrhage. Of these, nine were found to carry Chromosome 21 copy number gain (chr21:27,224,097-27,871,284, GRCh37/hg19) including the APP locus (APP-dup). In seven, Chromosome 5 copy number gain (Chr5: 24,786,234-29,446,070, GRCh37/hg19) (Chr5-CNG) cosegregated with the APP-dup. Both duplications co-localized to chromosome 18q21.1 and segregated in 25 pre-symptomatic carriers. Compared to non-carriers, asymptomatic carriers manifested cognitive decline in their mid-thirties. A third of the affected individuals carried a diagnosis of a dis-immune condition. CONCLUSION: APP extra dosage, even in isolation and when located outside chromosome 21, is pathogenic. The clinical presentation of APP duplication varies and may be gender specific, i.e., ICH in males and cognitive-behavioral deterioration in females. The association with immune disorders is presently unclear but may prove relevant. The implication of Chr5-CNG co-segregation and the surrounding chromosome 18 genetic sequence needs further clarification.

The First Word Recalled Measure - A Potential Addition to Clinical Exams.

Characterizing episodic memory abilities is highly important in the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI), and usually includes wordlist learning and recall tasks. Clinical evaluations typically focus on the number of words recalled, ignoring additional information, like serial position. Here, we tested the potential value of two serial positioning measures for clinical diagnosis - how retrieval is initiated, as measured by the first word recalled, and how it proceeds - using data from patients with AD and MCI that completed a wordlist learning and recall task. Our results show that during the early stages of learning, patients with AD are less prone to retrieve the first word from the wordlist, manifested as lower primacy effect in the first word recalled, compared with MCI patients. The first word recalled measure adds to the differentiation between the groups over and above the total number of words learned. Thus, the first word recalled during word list learning and recall tasks may be used as a simple complementary measure to distinguish between MCI and AD during standard neuropsychological evaluations.

Two systems for empathy: a double dissociation between emotional and cognitive empathy in inferior frontal gyrus versus ventromedial prefrontal lesions.

Recent evidence suggests that there are two possible systems for empathy: a basic emotional contagion system and a more advanced cognitive perspective-taking system. However, it is not clear whether these two systems are part of a single interacting empathy system or whether they are independent. Additionally, the neuroanatomical bases of these systems are largely unknown. In this study, we tested the hypothesis that emotional empathic abilities (involving the mirror neuron system) are distinct from those related to cognitive empathy and that the two depend on separate anatomical substrates. Subjects with lesions in the ventromedial prefrontal (VM) or inferior frontal gyrus (IFG) cortices and two control groups were assessed with measures of empathy that incorporate both cognitive and affective dimensions. The findings reveal a remarkable behavioural and anatomic double dissociation between deficits in cognitive empathy (VM) and emotional empathy (IFG). Furthermore, precise anatomical mapping of lesions revealed Brodmann area 44 to be critical for emotional empathy while areas 11 and 10 were found necessary for cognitive empathy. These findings are consistent with these cortices being different in terms of synaptic hierarchy and phylogenetic age. The pattern of empathy deficits among patients with VM and IFG lesions represents a first direct evidence of a double dissociation between emotional and cognitive empathy using the lesion method.