Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Background Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. Methods We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. Results The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. Conclusions Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.

Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer

PURPOSE Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. METHODS Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC – CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. RESULTS Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC – CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. CONCLUSION Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.

A-89 Age at First Psychiatric Hospitalization Predicts Deviation from Expected Cognitive Ability in Psychosis Spectrum Disorders

Objective The present study investigated whether clinical variables related to illness onset (age at symptom onset, diagnosis, first psychiatric hospitalization) predict deviation from expected cognitive ability. Additionally, we examined the potential moderating effect of psychosis groups (“biotypes”). Method Cognitive ability was predicted based on demographic variables and estimated premorbid intelligence modeled in controls. The degree to which current cognitive ability (based on Brief Assessment of Cognition in Schizophrenia) deviated from predicted ability was computed in 362 schizophrenia, schizoaffective, and bipolar with psychosis patients recruited from the community (Mage = 39.11; 52.2% male; 41.7% White, 41.4% Black, 16.9% Other). Linear regression assessed the relationship between illness onset and deviation scores and moderation analysis was performed using moderated multiple regression. Results Only age at first psychiatric hospitalization predicted deviation scores (F(1,328) = 3.93, p &lt; 0.05), such that younger individuals had a greater deviation from expected cognitive ability. The full moderated regression model significantly predicted deviation scores (F(5,330) = 14.05, p &lt; 0.001), and there was a significant effect of age at first psychiatric hospitalization and deviation scores only for biotype 3 (t = 7.37, p &lt; 0.001). Discussion Findings suggest that severity of illness at a younger age (requiring hospitalization), rather than earlier symptom onset, may be a risk factor for greater disruption of cognitive development. The association between group membership in biotype 3 (characterized by less cognitive impairment) and lower deviation scores may reflect reduced variability in deviation scores and less disruption of cognitive abilities than other biotypes. When assessing psychosis spectrum patients, clinicians should consider how factors related to illness onset and severity may impact developmental cognitive trajectories.

The Effect of CAG Repeats within the Non-Pathological Range in the HTT Gene on Cognitive Functions in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

The Huntingtin gene (HTT) is within a class of genes containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. Individuals with less than 35 repeats are not associated with HD. Increasing evidence has suggested that CAG repeats play a role in modulating brain development and brain function. However, very few studies have investigated the effect of CAG repeats in the non-pathological range on cognitive performances in non-demented individuals. In this study, we aimed to test how CAG repeats’ length influences neuropsychological scores in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We included 75 patients (46 SCD and 29 MCI). All patients underwent an extensive neuropsychological battery and analysis of HTT alleles to quantify the number of CAG repeats. Results: CAG repeat number was positively correlated with scores of tests assessing for executive function, visual–spatial ability, and memory in SCD patients, while in MCI patients, it was inversely correlated with scores of visual–spatial ability and premorbid intelligence. When we performed a multiple regression analysis, we found that these relationships still remained, also when adjusting for possible confounding factors. Interestingly, logarithmic models better described the associations between CAG repeats and neuropsychological scores. CAG repeats in the HTT gene within the non-pathological range influenced neuropsychological performances depending on global cognitive status. The logarithmic model suggested that the positive effect of CAG repeats in SCD patients decreases as the number of repeats grows.

Kognitív epidemiológia – Az intelligenciaszint prospektív összefüggése a szomatikus és pszichiátriai betegségrizikóval

A kognitív epidemiológia az intelligencia és az egészségi állapot összefüggésének tudo- mánya. A modern, sokszor több százezer fős, teljes populációkon végzett kognitív epide- miológiai vizsgálatok eredményei alapján a magasabb premorbid intelligencia gya- korlatilag valamennyi mentális betegség, illetve pszichiátriai probléma alacsonyabb kockázatával függ össze. A magasabb premorbid intelligencia a halálozás, a szív- és ér- rendszeri betegségek, a metabolikus betegségek, a rossz egészség-magatartás és számos kisebb népegészségügyi jelentőségű betegség előfordulásával is negatívan függ össze; a légzőszervi betegségekkel és a dohányzáshoz nem köthető daganatokkal azonban gyen- ge vagy hiányzik az összefüggés. A mentális betegségekkel való összefüggést nem, a szo- matikus betegségekkel és a mortalitással való összefüggést azonban részben mediálják a felnőttkori szocioökonómiai státusz mutatói. A speciális vizsgálati elrendezések – úgymint ikerkontroll-vizsgálatok, pszeudoexperimentális vizsgálatok, valamint a mendeli ran- domizáció módszerét használó molekuláris genetikai vizsgálatok – eredményei arra utal- nak, hogy az intelligencia és az egészség közötti kapcsolat jelentős részét genetikai ténye- zők közvetítik, de a szomatikus egészségre a magasabb intelligencia következményeként elérhető jobb szocioökonómiai státusz is szerény hatást gyakorol.Cognitive epidemiology is the science of the relationship between intelligence and health. Modern studies of cognitive epidemiology, often with samples of several hundreds of thousands of individuals, have revealed that higher premorbid intelligence is associated with a lower risk of virtually all of mental illnesses and psychiatric problems. Higher premorbid intelligence is also associated negatively with the incidence of mortality, circulatory illness, metabolic illness, poor health behavior and many diseases of lower epidemiological significance, but its relationship to respiratory illness and non-smoking related cancers is weaker or non-existent. Indicators of adult socioeconomic status do not mediate the association between intelligence and mental illness, but they do partially mediate the relationship with somatic illness and mortality. Studies with special designs -twin control studies, pseudo-experimental studies and molecular genetic studies using Mendelian randomization – suggest that the relationship between intelligence and health is heavily mediated by genetic factors, but somatic health may be modestly but causally improved by better social status as a consequence of higher intelligence.

Estimating premorbid intelligence in people living with dementia: a systematic review

ABSTRACT Objectives: In diagnosing dementia, estimating premorbid functioning is critical for accurate detection of the presence and severity of cognitive decline. However, which assessments of premorbid intelligence are most suitable for use in clinical practice is not well established. Here, we systematically evaluate the validity of instruments for measuring premorbid intelligence in people living with dementia. Design and setting: In this systematic review, electronic databases (EMBASE, PsycINFO, MEDLINE, CINAHL, and AMED) were searched to identify studies reporting on objective measures of premorbid intelligence in dementia. Participants from included studies were recruited from local communities and clinical settings. Participants: A total of 1082 patients with dementia and 2587 healthy controls were included in the review. Measurements: The literature search resulted in 13 eligible studies describing 19 different instruments. The majority of instruments (n = 14) consisted of language-based measures, with versions of the National Adult Reading Test (NART) being most commonly investigated. Results: Preliminary evidence suggested comparable performance of patients with mild dementia and healthy controls on word reading tasks in English, Portuguese, Swedish, and Japanese. In moderate dementia, however, the performance was significantly impaired on most verbal tasks. There was a lack of reliability and validity testing of available instruments, with only one of the included studies reporting psychometric properties within the patient group. Conclusions: The results demonstrate that there is a wide range of tools available for estimating premorbid intelligence in dementia, with cautious support for the potential of word reading tasks across different languages in individuals with mild dementia. However, the review highlights the urgent need for extensive assessments of the psychometric properties of these tasks in dementia. We propose that further longitudinal research and assessments of nonverbal measures are necessary to validate these instruments and enhance diagnostic procedures for people living with dementia worldwide.

Post-stroke Cognition at 1 and 3 Years Is Influenced by the Location of White Matter Hyperintensities in Patients With Lacunar Stroke

Lacunar strokes are a common type of ischemic stroke. They are known to have long-term cognitive deficits, but the influencing factors are still largely unknown. We investigated if the location of the index lacunar stroke or regional WMH and their change at 1 year could predict the cognitive performance at 1 and 3 years post-stroke in lacunar stroke patients. We used lacunar lesion location and WMH-segmented data from 118 patients, mean age 64.9 who had a brain MRI scan soon after presenting with symptoms, of which 88 had a repeated scan 12 months later. Premorbid intelligence (National Adult Reading Test) and current intelligence [Addenbrooke's Cognitive Exam-Revised (ACE-R)] were measured at 1, 12, and 36 months after the stroke. ANCOVA analyses adjusting for baseline cognition/premorbid intelligence, vascular risk factors, age, sex and total baseline WMH volume found that the recent small subcortical infarcts (RSSI) in the internal/external capsule/lentiform nucleus and centrum semiovale did not predict cognitive scores at 12 and 36 months. However, RSSI location moderated voxel-based associations of WMH change from baseline to 1 year with cognitive scores at 1 and 3 years. WMH increase in the external capsule, intersection between the anterior limb of the internal and external capsules, and optical radiation, was associated with worsening of ACE-R scores 1 and 3 years post-stroke after accounting for the location of the index infarct, age and baseline cognition.

Overlap Between Genetic Variants Associated With Schizophrenia and Intelligence Quotient: Protocol for a Systematic Review

BackgroundPeople with schizophrenia often exhibit a premorbid intelligence quotient (IQ) deficit. A genetic overlap between schizophrenia and IQ has been found, indicating shared genetic variants underlying the risk of schizophrenia and a low IQ. However, literature has emerged that offers contradictory findings about this issue. The aim of this systematic review will be to analyse and summarize the evidence that explores genetic variants associated with schizophrenia and IQ. MethodsA search will be carried out in four electronic databases (MEDLINE via PubMed, PsycINFO, Web of Science and Scopus). The search strategy will include terms related to “schizophrenia”, “genetic variants” and “intelligence quotient”, which will be adapted to medical subject headings (Mesh) format, Thesaurus format and free text. The team of reviewers will record the results in a bibliographic manager software and conduct the selection process. Observational studies examining human adults with schizophrenia that explore the association between genetic variants and the IQ of the participants will be considered. The risk of bias of the primary studies will be assessed using the genetic study quality tool (Q-Genie). After data extraction, the main results will be presented in a narrative synthesis.DiscussionThe findings of this systematic review may help us understand if there is genetic overlap between schizophrenia and IQ, and to identify specific genetic factors involved. Systematic review registrationPROSPERO CRD42020218842.

Causal associations of intelligence with schizophrenia and bipolar disorder: A Mendelian randomization analysis

Background Intelligence is inversely associated with schizophrenia (SCZ) and bipolar disorder (BD); it remains unclear whether low intelligence is a cause or consequence. We investigated causal associations of intelligence with SCZ or BD risk and a shared risk between SCZ and BD and SCZ-specific risk. Methods To estimate putative causal associations, we performed multi-single nucleotide polymorphism (SNP) Mendelian randomization (MR) using generalized summary-data-based MR (GSMR). Summary-level datasets from five GWASs (intelligence, SCZ vs. control [CON], BD vs. CON, SCZ + BD vs. CON, and SCZ vs. BD; sample sizes of up to 269,867) were utilized. Results A strong bidirectional association between risks for SCZ and BD was observed (odds ratio; ORSCZ → BD = 1.47, p = 2.89 × 10−41, ORBD → SCZ = 1.44, p = 1.85 × 10−52). Low intelligence was bidirectionally associated with a high risk for SCZ, with a stronger effect of intelligence on SCZ risk (ORlower intelligence → SCZ = 1.62, p = 3.23 × 10−14) than the reverse (ORSCZ → lower intelligence = 1.06, p = 3.70 × 10−23). Furthermore, low intelligence affected a shared risk between SCZ and BD (OR lower intelligence → SCZ + BD = 1.23, p = 3.41 × 10−5) and SCZ-specific risk (ORlower intelligence → SCZvsBD = 1.64, p = 9.72 × 10−10); the shared risk (ORSCZ + BD → lower intelligence = 1.04, p = 3.09 × 10−14) but not SCZ-specific risk (ORSCZvsBD → lower intelligence = 1.00, p = 0.88) weakly affected low intelligence. Conversely, there was no significant causal association between intelligence and BD risk (p > 0.05). Conclusions These findings support observational studies showing that patients with SCZ display impairment in premorbid intelligence and intelligence decline. Moreover, a shared factor between SCZ and BD might contribute to impairment in premorbid intelligence and intelligence decline but SCZ-specific factors might be affected by impairment in premorbid intelligence. We suggest that patients with these genetic factors should be categorized as having a cognitive disorder SCZ or BD subtype.