Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
J Int Neuropsychol Soc ; 30(5): 439-447, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38263745

RESUMEN

OBJECTIVE: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. METHOD: 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aß42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. RESULTS: Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. CONCLUSIONS: MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.


Asunto(s)
Disfunción Cognitiva , Pruebas Neuropsicológicas , Trastornos por Estrés Postraumático , Veteranos , Guerra de Vietnam , Proteínas tau , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Masculino , Anciano , Persona de Mediana Edad , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Pruebas Neuropsicológicas/normas , Proteínas tau/líquido cefalorraquídeo , Femenino , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/sangre , Anciano de 80 o más Años
2.
J Neuropsychiatry Clin Neurosci ; : appineuropsych20230119, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38988190

RESUMEN

OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.

3.
Alzheimers Dement ; 20(5): 3442-3454, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38574399

RESUMEN

INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.


Asunto(s)
Disfunción Cognitiva , Progresión de la Enfermedad , Pruebas Neuropsicológicas , Humanos , Disfunción Cognitiva/diagnóstico , Anciano , Femenino , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Análisis por Conglomerados , Anciano de 80 o más Años , Factores de Riesgo
4.
Alzheimers Dement ; 19(5): 2182-2196, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36642985

RESUMEN

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/patología , Encéfalo/patología , Biomarcadores , Progresión de la Enfermedad
5.
Learn Mem ; 29(10): 367-378, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36180130

RESUMEN

Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults (N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested.


Asunto(s)
Disfunción Cognitiva , Memoria Episódica , Anciano , Amnesia Retrógrada , Disfunción Cognitiva/diagnóstico , Humanos , Lenguaje , Pruebas Neuropsicológicas
6.
Magn Reson Med ; 87(4): 1816-1831, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34792198

RESUMEN

PURPOSE: The locus coeruleus (LC) is implicated as an early site of protein pathogenesis in Alzheimer's disease (AD). Tau pathology is hypothesized to propagate in a prion-like manner along the LC-transentorhinal cortex (TEC) white matter (WM) pathway, leading to atrophy of the entorhinal cortex and adjacent cortical regions in a progressive and stereotypical manner. However, WM damage along the LC-TEC pathway may be an earlier observable change that can improve detection of preclinical AD. THEORY AND METHODS: Diffusion-weighted MRI (dMRI) allows reconstruction of WM pathways in vivo, offering promising potential to examine this pathway and enhance our understanding of neural mechanisms underlying the preclinical phase of AD. However, standard dMRI analysis tools have generally been unable to reliably reconstruct this pathway. We apply a novel method, geometric-optics based entropy spectrum pathways (GO-ESP) and produce a new measure of connectivity: the equilibrium probability (EP). RESULTS: We demonstrated reliable reconstruction of LC-TEC pathways in 50 cognitively normal older adults and showed a negative association between LC-TEC EP and cerebrospinal fluid tau. Using Human Connectome Project data, we demonstrated replicability of the method across acquisition schemes and scanners. Finally, we compared our findings with the only other existing LC-TEC tractography template, and replicated their pathway as well as investigated the source of these discrepant findings. CONCLUSIONS: AD-related tau pathology may be detectable within GO-ESP-identified LC-TEC pathways. Furthermore, there may be multiple possible routes from LC to TEC, raising important questions for future research on the LC-TEC connectome and its role in AD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer , Locus Coeruleus , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Entropía , Humanos , Locus Coeruleus/diagnóstico por imagen , Locus Coeruleus/metabolismo , Locus Coeruleus/patología , Imagen por Resonancia Magnética , Proteínas tau/metabolismo
7.
J Neurovirol ; 28(1): 162-167, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35103880

RESUMEN

Given the co-occurrence of memory impairment in HIV-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment/Alzheimer's disease (aMCI/AD), biomarkers are needed that can disentangle these conditions among people with HIV (PWH). We assessed whether cerebrospinal fluid (CSF) markers of AD could help in this effort by determining their relationship to learning and memory deficits versus cognitive deficits more characteristic of HAND than aMCI/AD (processing speed and complex visual/motor coordination) among 31 older PWH. CSF amyloid-ß42 phosphorylated-tau, amyloid-ß40/amyloid-ß42 and phosphorylated-tau/amyloid-ß42 ratio related to learning/memory performance but not HAND-related deficits, suggesting that these biomarkers may have utility in disentangling aMCI/AD from HAND.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Infecciones por VIH , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/psicología , Infecciones por VIH/complicaciones , Humanos , Trastornos de la Memoria , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Proyectos Piloto , Proteínas tau/líquido cefalorraquídeo
8.
Aging Ment Health ; 26(12): 2440-2446, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34842012

RESUMEN

OBJECTIVES: To examine associations between alcohol use and cognitive performance among older adults in Greece and the United States, and assess potential differences due to differing drinking practices in the two countries. METHODS: Data came from Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) and National Alzheimer's Coordinating Center Uniform Dataset (NACC). We examined those aged 65-90 years at baseline who had no cognitive impairment and complete data for cognitive and alcohol use variables (N = 1110 from HELIAD; N = 2455 from NACC). We examined associations between current alcohol use and frequency of such use with cognitive performance on various cognitive tasks stratified by gender. RESULTS: In NACC, use of alcohol was associated with better cognitive performance. Men drinkers performed better than non-drinkers on Trail A (standardized mean 0.07 vs. -0.24, p<.001), Trail B (0.06 vs. -0.19, p=.001), and women drinkers performed better on Trail A (0.04 vs. -0.09, p=.016), Trail B (0.04 vs. -0.10, p=.005), verbal fluency (Animals: 0.05 vs. -0.13, p<.001; Vegetables: 0.04 vs. -0.09, p=.027), and MoCA (0.03 vs. -0.08, p=.039). In HELIAD, fewer differences were seen with only women drinkers exhibiting better performance than non-drinkers on the Boston Naming Task (0.11 vs. -0.05, p=.016). In general, more frequent drinkers performed better on cognitive tasks than less frequent drinkers, although this was only statistically significant in the NACC dataset. CONCLUSION: While drinking alcohol may be associated with better cognitive performance across both the US and Greece, more research is needed to assess the cultural factors that may modify this association.


Asunto(s)
Consumo de Bebidas Alcohólicas , Disfunción Cognitiva , Masculino , Estados Unidos/epidemiología , Humanos , Femenino , Anciano , Grecia/epidemiología , Consumo de Bebidas Alcohólicas/epidemiología , Envejecimiento , Disfunción Cognitiva/epidemiología , Etanol
9.
J Infect Dis ; 224(3): 435-442, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-33319235

RESUMEN

BACKGROUND: Memory impairment occurs in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment (aMCI), the precursor to Alzheimer disease (AD). Methods are needed to distinguish aMCI-associated from HAND-associated impairment in people with HIV (PWH). We developed a neuropsychological method of identifying aMCI in PWH and tested this by relating AD neuropathology (ß-amyloid, phospho-Tau) to aMCI versus HAND classification. METHODS: Seventy-four HIV-positive cases (aged 50-68 years) from the National NeuroAIDS Tissue Consortium had neurocognitive data within 1 year of death and data on ß-amyloid and phospho-Tau pathology in frontal brain tissue. High aMCI risk was defined as impairment (<1.0 SD below normative mean) on 2 of 4 delayed recall or recognition outcomes from a verbal and nonverbal memory test (at least 1 recognition impairment required). Differences in ß-amyloid and phospho-Tau by aMCI and HAND classification were examined. RESULTS: High aMCI risk was more common in HAND (69.0%) versus no HAND (37.5%) group. ß-amyloid pathology was 4.75 times more likely in high versus low aMCI risk group. Phospho-Tau pathology did not differ between aMCI groups. Neither neuropathological feature differed by HAND status. CONCLUSIONS: Amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.


Asunto(s)
Disfunción Cognitiva , Infecciones por VIH , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Infecciones por VIH/complicaciones , Humanos , Pruebas Neuropsicológicas
10.
Alzheimers Dement ; 17(10): 1756-1762, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33860596

RESUMEN

INTRODUCTION: Neurofilament light (NFL) reflects neuroaxonal damage and is implicated in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known about NFL in pre-MCI stages, such as in individuals with objectively-defined subtle cognitive decline (Obj-SCD). METHODS: Two hundred ninety-four participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent baseline blood draw and serial neuropsychological testing over 5 years of follow-up. RESULTS: Individuals with Obj-SCD and MCI showed elevated baseline plasma NFL relative to the cognitively normal (CN) group. Across the sample, elevated NFL predicted faster rate of cognitive and functional decline. Within the Obj-SCD and MCI groups, higher NFL levels predicted faster rate of decline in memory and preclinical AD composite score compared to the CN group. DISCUSSION: Findings demonstrate the utility of plasma NFL as a biomarker of early AD-related changes, and provide support for the use of Obj-SCD criteria in clinical research to better capture subtle cognitive changes.


Asunto(s)
Enfermedad de Alzheimer/sangre , Disfunción Cognitiva/sangre , Estado Funcional , Proteínas de Neurofilamentos/sangre , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino
11.
Alzheimers Dement ; 17(1): 61-69, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32886451

RESUMEN

INTRODUCTION: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. METHODS: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aß) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aß, including interactions with APOE ε4-carrier status. RESULTS: Adjusting for tau PET, Aß was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aß PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4-carriers, even among Aß-negative individuals. DISCUSSION: Findings suggest that APOE may interact with tau independently of Aß and that elevated MTL tau confers negative cognitive consequences in Aß-negative ε4 carriers.


Asunto(s)
Péptidos beta-Amiloides/genética , Apolipoproteínas E/metabolismo , Trastornos de la Memoria/diagnóstico por imagen , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Apolipoproteína E4/sangre , Apolipoproteínas E/genética , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Cognición , Demencia/genética , Demencia/psicología , Femenino , Heterocigoto , Humanos , Masculino , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Proteínas tau/genética
12.
Alzheimer Dis Assoc Disord ; 34(1): 10-17, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31305320

RESUMEN

OBJECTIVE: The current study examined the interactive effect of type 2 diabetes and Alzheimer disease (AD) risk factors on the rate of functional decline in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative. METHODS: Participants underwent annual assessments that included the Functional Activities Questionnaire, an informant-rated measure of everyday functioning. Multilevel modeling, controlling for demographic variables and ischemic risk, examined the interactive effects of diabetes status (diabetes, n=69; no diabetes, n=744) and AD risk factors in the prediction of 5-year longitudinal change in everyday functioning. One model was run for each AD risk factor, including: objectively-defined subtle cognitive decline (Obj-SCD), and genetic susceptibility [apolipoprotein E ε4 (APOE ε4) as well as cerebrospinal fluid ß-amyloid (Aß), total tau (tau), and hyperphosphorylated tau (p-tau). RESULTS: The 3-way diabetes×AD risk factor×time interaction predicted increased rates of functional decline in models that examined Obj-SCD, APOE ε4, tau, and p-tau positivity, but not Aß positivity. CONCLUSIONS: Participants with both diabetes and at least 1 AD risk factor (ie, Obj-SCD, APOE ε4, tau, and p-tau positivity) demonstrated faster functional decline compared with those without both risk factors (diabetes or AD). These findings have implications for early identification of, and perhaps earlier intervention for, diabetic individuals at risk for future functional difficulty.


Asunto(s)
Actividades Cotidianas , Disfunción Cognitiva , Diabetes Mellitus Tipo 2/complicaciones , Voluntarios Sanos , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteína E4/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Proteínas tau/líquido cefalorraquídeo
13.
Alzheimers Dement ; 16(7): 1013-1022, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32418367

RESUMEN

INTRODUCTION: We examined differences in cortical thickness in empirically derived mild cognitive impairment (MCI) subtypes in the Mayo Clinic Study of Aging. METHODS: We compared cortical thickness of four incident MCI subtypes (n = 192) to 1257 cognitive unimpaired individuals. RESULTS: The subtle cognitive impairment cluster had atrophy in the entorhinal and parahippocampal cortex. The amnestic, dysnomic, and dysexecutive clusters also demonstrated entorhinal cortex atrophy as well as thinning in temporal, parietal, and frontal isocortex in somewhat different patterns. DISCUSSION: We found patterns of atrophy in each of the incident MCI clusters that corresponded to their patterns of cognitive impairment. The identification of MCI subtypes based on cognitive and structural features may allow for more efficient trial and study designs. Given individuals in the subtle cognitive impairment cluster have less structural changes and cognitive decline and may represent the earliest group, this could be a unique group to target with early interventions.


Asunto(s)
Grosor de la Corteza Cerebral , Encéfalo/patología , Disfunción Cognitiva/epidemiología , Anciano , Anciano de 80 o más Años , Atrofia/diagnóstico por imagen , Atrofia/patología , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas
14.
Neuroimage ; 202: 116162, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31493534

RESUMEN

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) gene increases risk for cognitive decline in normal and pathologic aging. However, precisely how APOE ε4 exerts its negative impact on cognition is poorly understood. The present study aimed to determine whether APOE genotype (ε4+ vs. ε4-) modifies the interaction of medial temporal lobe (MTL) resting cerebral blood flow (CBF) and brain structure (cortical thickness [CT], volume [Vo]) on verbal memory performance. METHODS: Multiple linear regression models were employed to investigate relationships between APOE genotype, arterial spin labeling MRI-measured CBF and FreeSurfer-based CT and Vo in four MTL regions of interest (left and right entorhinal cortex and hippocampus), and verbal memory performance among a sample of 117 cognitively normal older adults (41 ε4+, 76 ε4-) between the ages of 64 and 89 (mean age â€‹= â€‹73). RESULTS: Results indicated that APOE genotype modified the interaction of CBF and CT on memory in the left entorhinal cortex, such that the relationship between entorhinal CBF and memory was negative (lower CBF was associated with better memory) in non-carriers with higher entorhinal CT, positive (higher CBF was associated with better memory) in non-carriers with lower entorhinal CT, and negative (higher CBF was associated with worse memory) in ε4 carriers with lower entorhinal CT. CONCLUSIONS: Findings suggest that older adult APOE ε4 carriers may experience vascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect memory even in the absence overt clinical symptoms, providing potential insight into the mechanistic link between APOE ε4 and detriments in cognition. Moreover, findings suggest a distinct multimodal neural signature in ε4 carriers (higher CBF and lower CT in the entorhinal cortex) that could aid in the identification of candidates for future clinical trials aimed at preventing or slowing cognitive decline. Differential findings with respect to ε4 carriers and non-carriers are discussed in the context of neurovascular compensation.


Asunto(s)
Apolipoproteínas E/fisiología , Corteza Cerebral/anatomía & histología , Corteza Entorrinal/irrigación sanguínea , Corteza Entorrinal/fisiología , Memoria/fisiología , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/fisiología , Circulación Cerebrovascular , Corteza Entorrinal/anatomía & histología , Femenino , Genotipo , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad
15.
J Int Neuropsychol Soc ; 25(8): 878-883, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31060638

RESUMEN

OBJECTIVES: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer's disease (AD) and other neurological disorders, including Huntington's disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. METHODS: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes - across-trial novel intrusions and across/within trial repeated intrusions - in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. RESULTS: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. CONCLUSIONS: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Función Ejecutiva , Enfermedad de Huntington/diagnóstico , Trastornos de la Memoria/diagnóstico , Pruebas de Memoria y Aprendizaje/normas , Desempeño Psicomotor , Aprendizaje Verbal , Anciano , Enfermedad de Alzheimer/complicaciones , Atención/fisiología , Función Ejecutiva/fisiología , Femenino , Humanos , Enfermedad de Huntington/complicaciones , Masculino , Trastornos de la Memoria/etiología , Recuerdo Mental/fisiología , Persona de Mediana Edad , Desempeño Psicomotor/fisiología , Reconocimiento en Psicología/fisiología , Aprendizaje Verbal/fisiología
16.
Alzheimers Dement ; 15(7): 878-887, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31128864

RESUMEN

INTRODUCTION: We evaluated whether incident mild cognitive impairment (MCI) subtypes could be empirically derived in the Mayo Clinic Study of Aging. METHODS: We performed cluster analysis on neuropsychological data from 506 participants with incident MCI. RESULTS: The 3-cluster solution resulted in (1) amnestic, (2) dysexecutive, (3) dysnomic subtypes. The 4-cluster solution produced these same three groups and a fourth group with subtle cognitive impairment (SCI). The SCI cluster was a subset of the amnestic cluster and distinct from well-matched cognitively unimpaired participants based on memory and global z-score area under the receiver operating characteristic curve analyses and probability of progression to MCI/dementia. DISCUSSION: We empirically identified three neuropsychological subtypes of MCI that share some features with MCI subtypes identified in the Alzheimer's Disease Neuroimaging Initiative. The fourth subtype with SCI in the Mayo Clinic Study of Aging differed from the fourth cluster-derived normal group in Alzheimer's Disease Neuroimaging Initiative and could represent a group to target with early interventions.


Asunto(s)
Envejecimiento , Análisis por Conglomerados , Disfunción Cognitiva/clasificación , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Estados Unidos
17.
Alzheimers Dement ; 15(5): 699-708, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30737119

RESUMEN

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) separates "early" and "late" mild cognitive impairment (MCI) based on a single memory test. We compared ADNI's MCI classifications to our neuropsychological approach, which more broadly assesses cognitive abilities. METHODS: Three hundred thirty-six ADNI-2 participants were classified as "early" or "late" MCI. Cluster analysis was performed on neuropsychological test data, and participants were reclassified based on cluster results. These two staging approaches were compared on progression rates, cerebrospinal fluid biomarkers, and cortical thickness profiles. RESULTS: There was little correspondence between the two staging methods. ADNI's early MCI group included a large proportion of false-positive diagnostic errors. The reclassified neuropsychological MCI groups showed steeper survival curves and more abnormal biomarkers. CONCLUSIONS: Our novel neuropsychological approach improved the staging of MCI by (1) capturing individuals at an early symptomatic stage, (2) minimizing false-positive cases, and (3) identifying a late MCI group further along the disease trajectory.


Asunto(s)
Biomarcadores , Disfunción Cognitiva/diagnóstico , Errores Diagnósticos/prevención & control , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano , Biomarcadores/líquido cefalorraquídeo , Análisis por Conglomerados , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Neuroimagen
18.
Alzheimers Dement ; 15(10): 1322-1332, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31495605

RESUMEN

INTRODUCTION: The low mild cognitive impairment (MCI) to cognitively normal (CN) reversion rate in the Alzheimer's Disease Neuroimaging Initiative (2-3%) suggests the need to examine reversion by other means. We applied comprehensive neuropsychological criteria (NP criteria) to determine the resulting MCI to CN reversion rate. METHODS: Participants with CN (n = 641) or MCI (n = 569) were classified at baseline and year 1 using NP criteria. Demographic, neuropsychological, and Alzheimer's disease biomarker variables as well as progression to dementia were examined across stable CN, reversion, and stable MCI groups. RESULTS: NP criteria produced a one-year reversion rate of 15.8%. Reverters had demographics, Alzheimer's disease biomarkers, and risk-of-progression most similar to the stable CN group and showed the most improvement on neuropsychological measures from baseline to year 1. DISCUSSION: NP criteria produced a reversion rate that is consistent with, albeit modestly improved from, reversion rates in meta-analyses. Reverters' biomarker profiles and progression rates suggest that NP criteria accurately tracked with underlying pathophysiologic status.


Asunto(s)
Cognición/fisiología , Disfunción Cognitiva , Neuroimagen , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano , Biomarcadores , Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Demografía , Femenino , Humanos
19.
Alzheimers Dement ; 15(4): 561-569, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30610833

RESUMEN

INTRODUCTION: We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 in addition to Alzheimer's disease biomarkers by group were examined. RESULTS: The MCI-to-CN reversion rate was 3.0%. When specific components were examined, 22.5% of stable MCI participants had normal memory performance at Year 1 and their Alzheimer's disease biomarkers were consistent with the stable CN group. At Year 1, when all MCI criteria were not met, the more subjective Clinical Dementia Rating rather than objective memory measure appeared to drive continuation of the MCI diagnosis. DISCUSSION: Results demonstrate an artificially low 1-year MCI-to-CN reversion rate in ADNI-diagnosed participants. If the Logical Memory cutoffs had been consistently applied, the reversion rate would have been at least 21.8%.


Asunto(s)
Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Neuroimagen , Pruebas Neuropsicológicas , Anciano , Biomarcadores/líquido cefalorraquídeo , Encéfalo , Femenino , Humanos , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas/normas , Pruebas Neuropsicológicas/estadística & datos numéricos , Estados Unidos , Proteínas tau/líquido cefalorraquídeo
20.
Dement Geriatr Cogn Disord ; 46(5-6): 253-265, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30391953

RESUMEN

BACKGROUND/AIMS: Mild cognitive impairment (MCI) lacks a "gold standard" operational definition. The Jak/Bondi actuarial neuropsychological criteria for MCI are associated with improved diagnostic stability and prediction of progression to dementia compared to conventional MCI diagnostic approaches, although its utility in diagnosing MCI in old-old individuals (age 75+) is unknown. Therefore, we investigated the applicability of neuropsychological MCI criteria among old-old from the Framingham Heart Study. METHODS: A total of 347 adults (ages 79-102) were classified as cognitively normal or MCI via Jak/Bondi and conventional Petersen/Winblad criteria, which differ on cutoffs for cognitive impairment and number of impaired scores required for a diagnosis. Cox models examined MCI status in predicting risk of progression to dementia. RESULTS: MCI diagnosed by both the Jak/Bondi and Petersen/Winblad criteria was associated with incident dementia; however, when both criteria were included in the regression model together, only the Jak/Bondi criteria remained statistically significant. At follow-up, the Jak/Bondi criteria had a lower MCI-to-normal reversion rate than the Petersen/Winblad criteria. CONCLUSIONS: Our findings are consistent with previous research on the Jak/Bondi criteria and support the use of a comprehensive neuropsychological diagnostic approach for MCI among old-old individuals.


Asunto(s)
Envejecimiento/psicología , Disfunción Cognitiva , Demencia , Pruebas Neuropsicológicas/normas , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Demencia/diagnóstico , Demencia/psicología , Progresión de la Enfermedad , Femenino , Evaluación Geriátrica/métodos , Humanos , Estudios Longitudinales , Masculino , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA