Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

peer reviewed[en] BACKGROUND AND OBJECTIVES: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI). METHODS: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181), total tau and Aβ42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD. RESULTS: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups. DISCUSSION: Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Background and ObjectivesTo determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI).MethodsThis study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-beta (A beta)42/A beta 40, phosphorylated tau (p-tau181), total tau and A beta 42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M +/- SD: 40.6 +/- 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD.ResultsIn our sample (N = 672, mean age: 70.7 +/- 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215;HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups.DiscussionOur results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD

Looking back - Looking forward : A novel multi-time slice weight-of-evidence approach for defining reference conditions to assess the impact of human activities on lake systems

Lake ecosystems are sensitive recorders of environmental changes that provide continuous archives at annual to decadal resolution over thousands of years. The systematic investigation of land use changes and emission of pollutants archived in Holocene lake sediments as well as the reconstruction of contamination, background conditions, and sensitivity of lake systems offer an ideal opportunity to study environmental dynamics and consequences of anthropogenic impact that increasingly pose risks to human well-being. This paper discusses the use of sediment and other lines of evidence in providing a record of historical and current contamination in lake ecosystems. We present a novel approach to investigate impacts from human activities using chemical-analytical, bioanalytical, ecological, paleolimnological, paleoecotoxicological, archeological as well as modeling techniques. This multi-time slice weight-of-evidence (WOE) approach will generate knowledge on conditions prior to anthropogenic influence and provide knowledge to (i) create a better understanding of the effects of anthropogenic disturbances on biodiversity, (ii) assess water quality by using quantitative data on historical pollution and persistence of pollutants archived over thousands of years in sediments, and (iii) define environmental threshold values using modeling methods. This technique may be applied in order to gain insights into reference conditions of surface and ground waters in catchments with a long history of land use and human impact, which is still a major need that is currently not yet addressed within the context of the European Water Framework Directive

Paleohydraulic reconstruction of a 40 kyr-old terrace sequence implies that water discharge was larger than today

The evolution of landscapes crucially depends on the climate history. This is particularly evident in South America where landscape responses to orbital climate shifts have been well documented. However, while most studies have focused on inferring temperature variations from paleoclimate proxy data, estimates of water budget changes have been complicated because of a lack of adequate physical information. Here, we present a methodology and related results, which allowed us to extract water discharge values from the sedimentary record of the 40 Ka-old fluvial terrace deposits in the Pisco valley, western Peru. In particular, this valley hosts a Quaternary cut-and-fill succession that we used, in combination with beryllium-10 (10Be)-based sediment flux, gauging records, channel geometries and grain size measurements, to quantitatively assess sediment and water discharge values c. 40 Ka ago in relation to present-day conditions. We compare these discharge estimates to the discharge regime of the modern Pisco River and find that the water discharge of the paleo-Pisco River, during the Minchin pluvial period c. 40 Ka ago, was c. 7–8 times greater than the modern Pisco River if considering the mean and the maximum water discharge. In addition, the calculations show that inferred water discharge estimates are mainly dependent on channel gradients and grain size values, and to a lesser extent on channel width measures. Finally, we found that the c. 40 Ka-old Minchin terrace material was poorer sorted than the modern deposits, which might reflect that sediment transport during the past period was characterized by a larger divergence from equal mobility compared to the modern situation. In summary, the differences in grain size distribution and inferred water discharge estimates between the modern and the paleo-Pisco River suggests that the 40 Ka-old Minchin period was characterized by a wetter climate and more powerful flood events