The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol.

BACKGROUND: Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion. METHODS: The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an "in-depth" visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a "brief" visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one "in-depth" visit, similar to the baseline visit of healthy relatives. DISCUSSION: This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions. TRIAL REGISTRATION: The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

Vocabulary changes in adulthood: Main findings and methodological considerations.

BACKGROUND: Vocabulary scores increase until approximately age 65 years and then remain stable or decrease slightly, unlike scores on tests of other cognitive abilities that decline significantly with age. AIMS: To review the findings on ageing-related changes in vocabulary, and to discuss four methodological issues: research design; test type; measurement; and vocabulary ability as a proxy for general intelligence. MAIN CONTRIBUTION: A discussion of cross-sectional and longitudinal research designs shows that cohort membership accounts for some but not all ageing-related changes in vocabulary, and that drop-out and test-retest effects do not alter conclusions regarding these changes. Test type affects age trends in vocabulary, and if researchers use only one test, they should choose a multiple-choice synonym test. While some authors suggest that vocabulary tests do not measure the same underlying ability in younger and older adults, more research of this suggestion is needed. A brief examination of the use of vocabulary ability as a proxy for general intelligence in healthy ageing and for premorbid abilities in dementia indicates that such practice is often questionable. CONCLUSIONS: Vocabulary knowledge increases through the mid-60s regardless of measurement method. However, there is little information on how word knowledge serves other verbal skills in old age, how and when adults learn new words, or how much exposure is necessary for meanings to remain in storage for a lifetime. Research of these issues may require new methodologies, as well as novel theoretical accounts of ageing-related effects on vocabulary. WHAT THIS PAPER ADDS: What is already known on this subject Unlike many cognitive abilities that decline with ageing, vocabulary knowledge continues to increase until approximately age 65, and then remains stable or decreases slightly. These findings have been replicated in different research designs and across languages. What this paper adds to existing knowledge The article presents a summary of findings on changes in vocabulary across adulthood, and a discussion of four key methodological issues: research design, test type, measurement, and the use of vocabulary ability as a proxy for general intelligence. What are the potential or actual clinical implications of this work? To better understand changes in vocabulary knowledge across adulthood, clinicians must be aware of methodological considerations that affect the field. Such considerations have direct clinical implications regarding the choice of vocabulary tests and their use as a proxy for other abilities in both healthy older adults and in individuals with dementia.

Memory impairment and Alzheimer's disease pathology in individuals with MCI who underestimate or overestimate their decline.

OBJECTIVES: The aim of this study was to examine whether the discrepancy between participant and informant estimation of memory decline can predict MCI prognosis. METHODS: Analyses involved data from individuals with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire. Participants who underestimated (N = 112) and overestimated (N = 157) their memory decline were compared on memory tasks, brain volume, and cerebrospinal markers, at study entry and after 24 months. RESULTS: Individuals who underestimated their memory decline performed more poorly on memory tests, had smaller hippocampus volume, and greater Alzheimer's disease pathology than did individuals who overestimated their cognitive decline. Longitudinal comparisons demonstrated that individuals who underestimated their decline deteriorated more significantly in memory and in brain measures. CONCLUSIONS: Underestimation of memory decline should raise clinicians' suspicion of the existence of AD pathology in individuals with MCI.

Distinguishing Dementia With Lewy Bodies From Alzheimer Disease: What is the Influence of the GBA Genotype in Ashkenazi Jews?

Cognitive deficits beyond memory impairment, such as those affecting language production or executive functioning, can be useful in clinically distinguishing between dementia syndromes. We tested the hypothesis that Ashkenazi Jewish (AJ) patients who have dementia with Lewy bodies (DLB) and carry glucocerebrosidase (GBA) mutations will have verbal fluency deficits different from those found in Alzheimer disease (AD), whereas AJ patients with DLB who have no GBA mutations will have similar deficits in verbal fluency to those found in AD. We compared performance in phonemic and semantic verbal fluency tasks in 44 AJ patients with DLB and 20 patients with AD, matched for age, education, and age of immigration. All groups were found to have a deficit in semantic verbal fluency. On conducting the phonemic task, patients with DLB who carried GBA mutations scored more poorly than patients with AD, whereas DLB-noncarriers performed similarly to patients with AD. We suggest that verbal fluency tasks could serve as a possible clinical marker to subtype patients with DLB, with phonemic fluency being a marker for GBA-associated DLB.

Dissociation in awareness of memory and language decline in Alzheimer's disease.

OBJECTIVES: The aim of this study was to examine awareness of decline in memory and in language in individuals with Alzheimer's disease (AD), by comparing participant and informant ratings, as well as these ratings and actual test performance. METHODS: We analyzed data from 149 individuals with AD enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire and performed memory and language tasks. RESULTS: Participants provided significantly lower assessments of decline than did informants for both memory and language. There was a negative association between informant ratings and memory test scores but no association between participant ratings and memory test scores. Both participant and informant ratings correlated negatively with performance on the language tests. Informant, but not participant, ratings contributed to the prediction of one memory variable beyond demographic factors. Participant ratings contributed to the prediction of language scores beyond demographic factors more than did informant ratings. CONCLUSIONS: The findings reflect better awareness of decline in language than of decline in memory in individuals with AD.

Technology makes older adults feel older.

The current study aims to examine the effect of technology use on the assessment of subjective age across the adult lifespan, with the assumption that using technology might make older people feel older. One-hundred and fifty-one participants (ages 18-83) assessed their subjective age before and after using familiar and unfamiliar applications on a touchscreen tablet. Subjective age was assessed either by line marking or by numerical response. The oldest participants felt older after the manipulation relative to their pre-manipulation baseline, unlike the youngest participants in the sample. This effect was stronger for the unfamiliar application than for the familiar application. We suggest that using technology evokes stereotype threat. Although this threat does not impair performance, it still changes self perception. These findings could have far-reaching implications for the well-being of older adults in an ever more technological world.

An investigation of the efficiency of the mini-Kingston standardized cognitive assessment-revised in classifying patients according to DSM-5 major and mild neurocognitive disorders due to possible Alzheimer's disease.

BACKGROUND: The aim of this study was to examine the efficiency of the mini-Kingston standardized cognitive assessment-revised (mini-KSCAr) in classifying patients according to DSM-5 major and mild neurocognitive disorders (NCD) due to possible Alzheimer's disease (AD). METHODS: Files of 85 individuals who were tested on the Kingston standardized cognitive assessment-revised were reviewed and scores were calculated for the mini-KSCAr. Medical history, psychiatric and physical status, basic and instrumental activities of daily living, as well as scores on the Cambridge cognitive examination-revised (CAMCOG-R), and the clinical dementia rating (CDR) scale were used to establish DSM-5 diagnoses of major or mild neurocognitive disorders (NCD) due to possible AD or no cognitive decline. All participants were tested on the Mini-Mental State Examination (MMSE) and the clock drawing test (CDT), and a subset (N = 28) were also tested on three well-known memory tasks. RESULTS: Scores on the MMSE, CDT, and mini-KSCAr differed across groups, but only the mini-KSCAr significantly distinguished each group from the other two. The mini-KSCAr showed better sensitivity, specificity, and likelihood ratios (LRs) than did the MMSE and the CDT. A regression analysis revealed that the mini-KSCAr accounted for almost half of the variance in memory performance, whereas the MMSE and the CDT contributed nothing to this prediction once the mini-KSCAr was used. CONCLUSIONS: The mini-KSCAr is an efficient instrument for the diagnosis of DSM-5 major and mild NCD due to possible AD in a specialized psychogeriatric setting, and its utility is greater than that of the MMSE and the CDT.

Stronger left-hemisphere lateralization in older versus younger adults while processing conventional metaphors.

Thirty younger (age 20-30) and 30 older (age 69-85) right-handed Hebrew speakers performed a semantic judgement task while processing literal word pairs and conventional metaphors, presented in the divided visual field paradigm. Older adults responded more accurately to conventional metaphors in the right visual field/left hemisphere versus the left visual field/right hemisphere, whereas younger adults showed no lateralization. Vocabulary scores cancelled group differences in lateralization. An additional lexical decision task replicated the main finding of left-hemisphere lateralization in older but not in younger participants. We suggest that accumulated knowledge increases left-hemisphere lateralization on tasks of language comprehension in older relative to younger adults.

Perspective judgment across adulthood: Evidence from bilinguals.

Judging the perspective of others often requires ignoring one's own accessible knowledge. Aging increases reliance on the most available knowledge and may decrease the adjustment of this knowledge to adopt another perspective. Using a dominant language also decreases control demands, while using a nondominant language promotes deliberation. We examined whether aging and language dominance shape the way in which individuals judge someone else's interpretation of ambiguous messages. Russian-Hebrew bilinguals (N = 237, ages 19-80) read 20 ambiguous messages and judged how a recipient would interpret them. Half of the texts contained information that suggested that the message was sincere, and half of the texts contained information that implied that the message was sarcastic. This information was available only to the participant and should not have affected the recipient's interpretation. An egocentric bias emerged in both languages since participants could not ignore their own knowledge when judging the recipient's perspective. Aging was associated with a greater bias, but the results were similar in both languages. A second study included 60 younger (ages 18-39) and 62 older (ages 60-80) Israeli-born participants, who performed the same task as well as a flanker task (i.e., judging the direction of a central arrow flanked by congruent and incongruent distractors). Age interacted with the egocentric bias, but there was no correlation between the flanker effect and perspective judgment. Thus, decreased inhibition, as measured by the flanker task, cannot account for the egocentric bias. We suggest that the findings reflect difficulty in overriding highly accessible information, especially in older age. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Long-term cognitive outcomes in Susac syndrome: A case series.

Susac syndrome (SuS) presents with encephalopathy, visual disturbances, and hearing loss from immune-mediated microvascular occlusion. While acute SuS is well-described, long-term cognitive outcomes with current treatments are underknown. We assessed ten SuS patients treated in accordance with evidence-based guidelines using immunotherapies targeting humoral and cell-mediated pathways. Patients were followed for a median 3.6 years. Initially, cognition inversely correlated with corpus callosum lesions on MRI. All reported cognitive improvement; 5/10 patients had residual deficits in visual attention and executive function. Early, aggressive treatment was associated with good outcomes; extensive early corpus callosum lesions may identify patients at-risk of persistent cognitive deficits.

Environmental contributions to preschoolers' semantic fluency.

Semantic fluency was examined in Hebrew-speaking 5-year-old monozygotic and dizygotic twins (N = 396, 198 pairs), 22% of them with mother-reported speech-related problems. There were positive correlations of similar magnitudes among monozygotic, same-sex dizygotic, and opposite-sex dizygotic twins. Analyses showed no genetic effects, alongside significant shared (39%) and non-shared environmental (61%) effects on fluency scores. The presence of speech-related problems in one twin affected the fluency score of the co-twin. A multivariate regression analysis revealed that parental education and length of stay at daycare significantly predicted fluency scores. We suggest that semantic fluency performance is highly affected by environmental factors at age 5 although genetic effects might emerge later on.

Differences Between Semantic and Phonemic Verbal Fluency in Adolescents With Reading Disorders.

OBJECTIVES: This study aimed to examine which verbal fluency task is most useful in assessing adolescents with reading disorders (RD). METHOD: Eighty-three Hebrew-speaking adolescents (ages 12-15), 42 of them with RD, completed semantic and phonemic fluency tasks, and their scores were converted to standardized scores according to population norms. RESULTS: Scores on the semantic task were similar in the RD and the control group, unlike scores on the phonemic task, which were significantly lower in the RD group. The RD group demonstrated higher semantic than phonemic scores, unlike the control group whose standardized scores on both tasks were similar. Phonemic but not semantic fluency scores predicted spelling scores within the RD group. CONCLUSIONS: Adolescents with RD have no difficulty on a semantic fluency task, but perform below expected age-matched levels on the phonemic fluency task. To document this task-difference, practitioners must administer both fluency tasks when assessing RD.

The number of different digits determines solution and verification of multiplication problems.

The solution and verification of single-digit multiplication problems vary in speed and accuracy. The current study examines whether the number of different digits in a problem accounts for this variance. In Experiment 1, 41 participants solved all 2-9 multiplication problems. In Experiment 2, 43 participants verified these problems. In Experiment 3, 26 participants solved 10 problems that differed in shared-digit network (SDN) size and matched in problem size. In Experiment 4, 24 participants verified these matched sets. Results show faster and more accurate responses to problems that include fewer different digits relative to problems with more different digits, and faster and more accurate responses to problems whose SDN is small relative to problems whose SDN is large. We thus show that the number of different digits in a problem, including the operands and the solution, determines the speed and accuracy of its solution and verification. This parsimonious account also explains why responses to five and tie problems, which include fewer different digits relative to nonfive and nontie problems, are faster and more accurate than responses to other problems. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preserved morphological processing in semantic dementia.

Individuals with semantic dementia (SD) show progressive worsening of lexical-conceptual single word knowledge alongside preservation of nonsemantic aspects of language. The current study examines morphological processing in SD. S.H.S., a Hebrew-speaking person with SD, completed eight tasks that tested inflection, linear derivation, and nonlinear derivation at three time points over six and a half years. S.H.S. correctly produced plural nouns and judged the grammaticality of noun-verb and noun-adjective inflectional agreement. A steeper decline was seen in the ability to judge irregularly versus regularly inflected forms. S.H.S. judged nationality suffixes accurately and produced diminutive and agentive suffixes successfully. He also relied on morphological decomposition when performing lexical decision. Judgement of sentences consisting of derived verbal participles was intact with regard to morphological considerations alone, but impaired when semantic considerations determined grammaticality. S.H.S.'s performance suggests that structural aspects of word knowledge might be functional in the face of a severe semantic impairment.

Entrepreneurial tendency across the adult lifespan.

This study examines whether age associates with entrepreneurship tendencies across the lifespan, after taking into account aspects of personality that affect entrepreneurship. Participants (N = 963) aged 18-81, including 200 actual entrepreneurs, completed questionnaires about entrepreneurship tendency, personality traits, and attachment orientations. Results show that age is associated with a reduced tendency to engage in entrepreneurial activity. However, this decline is quite limited, it weakens with age, and is absent after age 50. In addition, the negative association of age with entrepreneurial tendency is smaller in participants with above-median entrepreneurship tendency scores relative to those with below-median scores, and it disappears in actual entrepreneurs. Furthermore, most of the traits that have been previously associated with entrepreneurial tendencies, especially Openness to Experience and Extraversion, remain unchanged with age, accounting for the stability of entrepreneurial tendency over time. The results have implications for policy makers who wish to encourage older adults to engage in entrepreneurial activity.

Explaining vocabulary knowledge in adulthood through comparison with knowledge of math concepts.

Previous research has assumed that all types of semantic knowledge are similarly affected by aging. We investigate whether knowledge of vocabulary and math concepts show comparable lifetime change. A sample of 252 participants aged 17-91 completed two multiple-choice tasks that examined knowledge of infrequent word meanings and knowledge of basic math concepts. Up to age 64, vocabulary scores improved, whereas math scores remained stable. After that age, vocabulary scores remained stable, while math scores declined. We suggest that the fact that the learning and use of infrequent vocabulary are incidental, incremental, and contextual contributes to maintenance of word knowledge into old age. In contrast, learning of basic math concepts occurs relatively early in life in an intentional manner, and both learning and use of these concepts involve constrained contexts. Thus, the nature of the acquisition and use of semantic knowledge across the lifespan affects its fate in old age.

On the importance of using local tests and local norms in the assessment of memory.

The current study compared the assessment of memory with a translated story recall test and its original published norms and an equivalent local test with local norms. Analyses used data from 232 individuals with memory complaints who underwent neuropsychological evaluation at an outpatient memory clinic. One group of participants completed a translated test (N = 126) and another group completed a local test (N = 106). Additionally, participants completed tasks of word list recall, picture naming, and verbal fluency, all having local norms. The results showed that raw scores on the delayed story recall test, and on all other cognitive tasks, did not differ across groups, and the cross-task correlations were significant and similar in size in both groups. Yet, there was an interaction between group and standardized tests scores, whereby the standardized scores on the translated story recall test were equivalent to population mean, whereas all other scores fell below the mean. Conversion of raw scores to the original norms indicated that the performance of individuals with memory complaints was intact, while conversion of scores on a local test to local norms revealed the expected memory impairment. The findings highlight the importance of using local tests and local norms in the assessment of memory.

The Association Between Views of Aging and Subjective Cognitive Complaints in Older Adults: Findings From Two Samples.

This cross-sectional study examined whether views of aging (VoA) relate to subjective cognitive complaints in two separate cohorts of older adults. Ageist attitudes, attitudes to aging (psychological loss, physical change, and psychological growth), subjective age, and subjective successful aging were examined. A moderating effect of chronological age was also examined. Samples included 572 adults aged 50 or older (Sample 1; mean age = 67.63, SD = 11.39, 49.4% female) and 224 adults aged 65 or older (Sample 2; mean age = 81.50, SD = 6.61, 75.3% female). More negative VoA (higher ageist attitudes, lower psychological growth, lower physical change, older subjective age, and less successful aging) were associated with more subjective cognitive complaints after controlling for covariates. An increase in chronological age strengthened some of these associations. Findings suggest that improving dimensions of VoA may have a complementary positive effect on subjective cognitive complaints in older adults.

Subjective Age and Late-Life Functional Status: Mediating and Moderating Effects.

OBJECTIVES: This study examined the longitudinal relationships between subjective age (SA) and future functional status in later life, via depressive symptoms. Additionally, we assessed the role of subjective nearness to death (SNtD) as a potential moderator within these pathways. METHODS: Older adults (average age 81.14 years at T1) were interviewed once a year for 3 consecutive years (N = 224 at T1, N = 178 at T2, and N = 164 at T3). Participants reported their SA, SNtD, depressive symptoms, and functional status. Additionally, grip strength was employed as an objective measure of functional status. RESULTS: Data analysis revealed distinct pathways leading from T1 SA to T3 functional status through T2 depressive symptoms. Moreover, T1 SNtD was found to significantly moderate most of these indirect pathways, so that the mediation model of T1 SA-T2 depressive symptoms-T3 functional status was mostly significant among those who felt closer to death. DISCUSSION: The findings contribute to our understanding of the underlying mechanism through which SA predicts long-term functioning sequelae by underscoring the indirect effect of depressive symptoms. They further indicate the importance of gauging the effects of SNtD on these longitudinal relationships. Present results may further contribute to establishing an integrative model for predicting long-term functional outcomes based on older adults' earlier subjective views of aging.