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BACKGROUND: Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). METHODS: Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. RESULTS: Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P = .040). Hispanic participants endorsed more depressive symptoms at baseline (P = .048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P = .023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (ß = .40 SE: .17, P = .023), and in specific BCRS domains: concentration (ß = .13, SE: .07, P = .047), past memory (ß = .13, SE: .06, P = .039) and functional abilities (ß = .10, SE: .05, P = .037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (ß = -.27, SE: .13, P = .039), MoCA (ß = -.80 SE: .34, P = .032), Trails A (ß = 2.75, SE: .89, P = .002), Trails B (ß = 9.18, SE: 2.71, P = .001) and Guild Paragraph Recall Delayed (ß = -.80 SE: .28, P = .005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.
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OBJECTIVES: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting-state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. METHODS: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. RESULTS: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity.
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Sinais (Psicologia) , Transtorno Depressivo Maior/complicações , Hipocampo/patologia , Deficiências da Aprendizagem , Vias Neurais/fisiopatologia , Descanso , Semântica , Adolescente , Aprendizagem por Associação/fisiologia , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Deficiências da Aprendizagem/diagnóstico por imagem , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/patologia , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Oxigênio/sangue , Escalas de Graduação Psiquiátrica , Análise de Regressão , Adulto JovemRESUMO
OBJECTIVES: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. METHODS: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. RESULTS: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. CONCLUSIONS: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.
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Aprendizagem por Associação/fisiologia , Córtex Cerebral/diagnóstico por imagem , Sinais (Psicologia) , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/patologia , Deficiências da Aprendizagem/etiologia , Sistema Límbico/diagnóstico por imagem , Semântica , Adolescente , Adulto , Idoso , Análise de Variância , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Deficiências da Aprendizagem/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
We evaluated risk factor differences and cognitive domain markers associated with progression in subjects with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer Disease Research Center. We included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline. Overall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) vs. 17.3 (2.1)), Hispanic ethnicity (50.0% vs. 11.0%), and hypercholesterolemia (aOR: 6.67), p ≤ 0.05 for all, were risk factors for progression in SCD, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all). These findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.
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Memory difficulties are consistently reported in Major Depressive Disorder (MDD). Nonetheless, it has not been thoroughly investigated as to whether these deficits persist during remission from MDD. A group of 32 healthy young adults with no history of a mood disorder (Mage = 20.8, SD = 2.1) and 62 remitted depressed young adults (Mage = 21.1, SD = 1.9) completed a neuropsychological battery. The test battery included two measures of nonverbal memory, two measures of verbal memory, and a measure of performance validity. The testing session was repeated three to six weeks later to determine performance stability. No differences were found between healthy controls and remitted depressed patients in either memory domain (all ps > .05) and improvement in performance was exhibited over time for both groups (p = 0.004). Potential practice effects are examined. We found a stronger performance for women than men (p = 0.003), particularly for the Semantic List Learning Task (SLLT) (p = .047). Verbal and nonverbal memory and effort may not be impacted in those who are in a remitted state of MDD, early in the course of the illness. Women demonstrated auditory memory superiority over men, similar to prior research.
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Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtornos da Memória/fisiopatologia , Desempenho Psicomotor/fisiologia , Adulto , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Feminino , Seguimentos , Humanos , Masculino , Transtornos da Memória/complicações , Indução de Remissão , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. OBJECTIVE: Two-year interval behavioral markers were investigated herein. METHODS: Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12±8.75 years, with a mean educational background of 15.55±2.60 years, and mean baseline MMSE scores of 28.9±1.24 were followed for 2.13±0.30 years. RESULTS: Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (pâ<â0.001), with component declines in Remote memory (pâ<â0.01), and Functioning/self-care (pâ=â0.01). CONCLUSION: SCD(I) persons decline at an annual rate of approximately 6.7% /year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.
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Comportamento , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Afeto , Idoso , Ansiedade/complicações , Ansiedade/psicologia , Biomarcadores , Depressão/complicações , Depressão/psicologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Psicometria , Autocuidado , Resultado do TratamentoRESUMO
Poor cognitive control (CC) is common among older individuals with major depressive disorder (OMDD). At the same time, studies of CC in OMDD with fMRI are relatively limited and often have small samples. The present study was conducted to further examine poor CC in OMDD with early onset depression, as well as to investigate the interactive effects of MDD and aging on cognitive control. Twenty OMDD, 17 older never-depressed comparisons (ONDC), 16 younger adults with MDD (YMDD), and 18 younger never-depressed comparisons (YNDC) participated. All participants completed the Go level of the Parametric Go/No-Go Test, which requires sustained attention and inhibitory control while undergoing functional MRI (fMRI). YNDC were faster in reaction times (RTs) to go targets relative to the other 3 groups, and the YMDD group was faster than the OMDD group. fMRI effects of both age and diagnosis were present, with greater activation in MDD, and in aging. Additionally, the interaction of age and MDD was also significant, such that OMDD exhibited greater recruitment of fronto-subcortical regions relative to older comparisons. These results are consistent with prior research reporting that OMDD recruit more fronto-striatal regions in order to perform at the same level as their never-depressed peers, here on a task of sustained attention and inhibitory control. There may be an interaction of cognitive aging and depression to create a double burden on the CC network in OMDD, including possible fronto-striatal compensation during CC that is unique to OMDD, as younger MDD individuals do not show this pattern.
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Envelhecimento/psicologia , Cognição , Transtorno Depressivo Maior/psicologia , Adolescente , Adulto , Idade de Início , Idoso , Atenção/fisiologia , Mapeamento Encefálico , Estudos de Casos e Controles , Cognição/fisiologia , Depressão/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tempo de Reação , Adulto JovemRESUMO
INTRODUCTION: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults. METHOD: The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown-Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated. RESULTS: Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex. CONCLUSIONS: This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.
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Encéfalo/fisiologia , Rememoração Mental/fisiologia , Semântica , Aprendizagem Verbal/fisiologia , Adolescente , Adulto , Idoso , Análise de Variância , Encéfalo/irrigação sanguínea , Sinais (Psicologia) , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Individualidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiologia , Testes Neuropsicológicos , Oxigênio/sangue , Reconhecimento Psicológico , Fatores de Tempo , Adulto JovemRESUMO
Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control.