A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.     

Prospective memory on a novel clinical task in older adults with mild cognitive impairment and subjective cognitive decline

Despite the relevance of prospective memory to everyday functioning and the ability to live independently, prospective memory tasks are rarely incorporated into clinical evaluations of older adults. We investigated the validity and clinical utility of a recently developed measure, the Royal Prince Alfred Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented, community-dwelling sample of 257 older adults (mean age = 80.78?years, 67.7% female) with amnestic mild cognitive impairment (aMCI, n = 18), nonamestic mild cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83) despite intact performance on traditional episodic memory tests, and healthy controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse than controls on the RPA-ProMem and its subtasks (time-based, event-based, short-term, long-term). Also, those with SCD scored significantly lower than controls on long-term, more naturalistic subtasks. Additional results supported the validity and inter-rater reliability of the RPA-ProMem and demonstrated a relation between test scores and informant reports of real-world functioning. The RPA-ProMem may help detect subtle cognitive changes manifested by individuals in the earliest stages of dementia, which may be difficult to capture with traditional episodic memory tests. Also, assessment of prospective memory can help guide the development of cognitive interventions for older adults at risk for dementia.     

Implementation of subjective cognitive decline criteria in research studies

Introduction

Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed.

Impaired digit span can predict further cognitive decline in older people with subjective memory complaint: a preliminary result

Subjective memory complaint (SMC) is common among elderly people, and is thought to be part of mild cognitive impairment (MCI). We evaluated whether impaired digit span (IDS) in older people with SMC can predict wider impairment in future neuropsychological tests that correspond to MCI. After a mean of 6.6 years from the initial assessment, we reevaluated 16 subjects with SMC and normal digit span (NDS) scores (mean age 57.6 ± 8.1 years) and 28 subjects with SMC and IDS scores (mean age 59.7 ± 9.9 years). The IDS group showed wider cognitive decline in tests of short-term verbal memory and category verbal fluency compared to the NDS group. IDS scores indicate an earlier step for conversion of SMC to MCI.     

The effect of schooling on reported age of onset of cognitive decline: A collaborative study

Higher education has been reported to be a protective factor against dementia. We suggest that the strength of a risk factor may be measured by the length of time by which it delays disease onset; therefore, we examined whether people with lower education develop cognitive decline at an earlier age than people with more schooling. The study population was based on patients referred to our Memory Clinics from 1994 to 2004. Analysis of covariance was used to evaluate the effect of schooling on the reported age of memory decline, in patients with mild cognitive impairment (MCI) and in patients diagnosed with Alzheimer’s disease (AD). The mean reported age of onset of cognitive decline was unexpectedly lower in patients with higher education than in patients with fewer schooling years, with a relatively small effect size (beta = −0.6), and the effect was more marked in the MCI group. Every year of schooling advanced the reported age of onset by 6 months among patients with MCI (t = −6.18, p < .001) and by 3 months among patients with AD (t = −2.4, p = 0.017). Education may affect the reported age of onset of cognitive decline, but its magnitude is small. It is possible that increased awareness in more educated people leads them to consult earlier; this could explain the paradoxical finding of earlier reported age of onset of cognitive decline in patients with higher education.     

Association between sleep quality and subjective cognitive decline: evidence from a community health survey

ObjectivesLittle is known concerning whether subjective cognitive decline (SCD) is associated with sleep quality. This study aimed to identify the association between self-reported quality of sleep and SCD in a large population of middle-aged and older adults in Korea.MethodsWe conducted this study based on data collected from the 2018 Korean Community Health Survey. Individuals aged 40 years and older who responded to the Behavioral Risk Factor Surveillance System (BRFSS) and Pittsburgh Sleep Quality Index (PSQI) assessments and did not lack data about multiple covariates were included. A total of 37,712 respondents with SCD and 135,119 those without SCD were included. Sleep quality was estimated using the PSQI, which includes seven self-reported components for sleep health assessment. SCD was assessed using the BRFSS. Logistic regression models adjusted for confounders were used to examine whether each component of the sleep quality index was related to SCD. Additional analysis of the correlation between quantified scores for each component and SCD-related functional limitations as ordinal variables was performed.ResultsThe mean age was 62.7 years in the SCD group and 56.4 years in the control group. In total, 13,777 (28.9%) respondents were male in the SCD group and 62,439 (50.7%) in the control group. The adjusted odds ratios of SCD were 1.25 for very bad sleep quality, 1.26 for long sleep latency, 1.16 for <5 h of sleep duration, 1.08 for <65% habitual sleep efficiency, 2.29 for high sleep disturbance, 1.26 for use of sleep medication ≥3 times a week, and 2.47 for high daytime dysfunction due to sleep problems compared to good sleep conditions. Furthermore, a higher score for each component of the sleep quality index correlated with greater SCD-related functional limitations.ConclusionsOur study provides evidence that poor sleep quality is closely related to both SCD and SCD-related functional limitations.     

Is brain connectome research the future frontier for subjective cognitive decline? A systematic review

ObjectiveWe performed a systematic literature review on Subjective Cognitive Decline (SCD) in order to examine whether the resemblance of brain connectome and functional connectivity (FC) alterations in SCD with respect to MCI, AD and HC can help us draw conclusions on the progression of SCD to more advanced stages of dementia.MethodsWe searched for studies that used any neuroimaging tool to investigate potential differences/similarities of brain connectome in SCD with respect to HC, MCI, and AD.ResultsSixteen studies were finally included in the review. Apparent FC connections and disruptions were observed in the white matter, default mode and gray matter networks in SCD with regards to HC, MCI, and AD. Interestingly, more apparent connections in SCD were located over the posterior regions, while an increase of FC over anterior regions was observed as the disease progressed.ConclusionsElders with SCD display a significant disruption of the brain network, which in most of the cases is worse than HC across multiple network parameters.SignificanceThe present review provides comprehensive and balanced coverage of a timely target research activity around SCD with the intention to identify similarities/differences across patient groups on the basis of brain connectome properties.     

The role of cognitive function and physical activity in physical decline in older adults across the cognitive spectrum

Objectives: The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum.

Methods: Physical function was assessed using the Physiological Profile Assessment (PPA) in 593 participants (cognitively normal [CN]: n = 342, mild cognitive impairment [MCI]: n = 77, dementia: n = 174) at baseline and in 490 participants available for reassessment 1-year later. Neuropsychological performance and physical activity (PA) were assessed at baseline.

Results: Median baseline PPA scores for CN, MCI and dementia groups were 0.41 (IQR = ?0.09–1.02), 0.66 (IQR = ?0.06–1.15) and 2.37 (IQR = 0.93–3.78) respectively. All baseline neuropsychological domains and PA were significantly associated with baseline PPA. There were significant interaction terms (Time × Cognitive Group, Global Cognition, Processing Speed, Executive Function and PA) in the models investigating PPA decline. In multivariate analysis the Time × Executive Function and PA interaction terms were significant, indicating that participants with poorer baseline executive function and reduced PA demonstrated greater physical decline when compared to individuals with better executive function and PA respectively.

Discussion: Having MCI or dementia is associated with greater physical decline compared to CN older people. Physical inactivity and executive dysfunction were associated with physical decline in this sample, which included participants with MCI and dementia. Both factors influencing physical decline are potentially amenable to interventions e.g. exercise.     

The role of diet in cognitive decline

Summary. Recent findings suggest a possible role of diet in age-related cognitive decline, and cognitive impairment of both degenerative (Alzheimer's disease, AD) or vascular origin. In particular, in an older population of Southern Italy with a typical Mediterranean diet, high monounsaturated fatty acids energy intake appeared to be associated with a high protection against cognitive decline. In addition, dietary fat and energy in older people seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in the European and North American countries. Moreover, foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD. Vitamin deficiencies, especially vitamin B6, B12 and folates, and antioxidant deficiencies (vitamins E and C) could also influence the memory capabilities and have an effect on cognitive decline. Dietary anti-oxidants and supplements and specific macronutrients of the diet may act synergistically with other protective factors opening new possibilities of intervention for cognitive decline. Received March 7, 2002; accepted June 12, 2002 Published online August 22, 2002 Acknowledgements This study was supported by Italian Longitudinal Study on Ageing (ILSA) (Italian National Research Council – CNR-Targeted Project on Ageing – Grants 9400419PF40 and 95973PF40), by Targeted Project on Mediterranean Diet (Italian National Research Council – CNR), by MURST 40% and 60%, by CARSO Consortium, Cancer Research Center, University of Bari, and by AFORIGE (“Associazione per la FOrmazione e la RIcerca in Geriatria”). VS and FP participate in the Ph.D.: “Carcinogenesis, Ageing, and Immunoregulation”, supported by European Union. The authors wish to thank Ms D. Calamita, Ms N. Lobascio, Dr G. Castellaneta, and Dr A. Terralavoro, Pfizer Inc., for skilful assistance. Authors' address: F. Panza, M.D., Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Piazza Giulio Cesare, 11, I-70124 Bari, Italy, e-mail: geriat.dot@geriatria.uniba.it     

事件相关诱发电位对阿尔茨海默病与轻度认知功能障碍的诊断价值

目的 探讨事件相关诱发电位(event-related potentials,ERPs)对阿尓茨海默病(Alzheimer's disease,AD)和轻度认知功能障碍(mild cognitive impairment,MCI)的诊断价值.方法 前瞻性的研究130例受试者,分3组:AD组60例,MCI组35例,和正常...     

Leg length, cognitive impairment and cognitive decline in an African-Caribbean population

BACKGROUND: Shorter leg length is associated with an adverse environment in early childhood and has been found to be associated with a variety of disorders occurring in mid- to late-life, including dementia in a Korean population. In a community population of African-Caribbean elders, in whom leg length had been measured, we sought to compare associations with cognitive impairment at baseline and cognitive decline over a three-year follow-up period. METHODS: Of 290 African-Caribbean residents in south London recruited at baseline, 216 (74%) were re-interviewed after a three-year period and 203 had sufficient data for this analysis. Cognitive impairment was derived as a binary category from a battery of cognitive tests administered at baseline and cognitive decline was derived from change in performance on a subset of these tests. Leg length (iliac crest to lateral malleolus) was also measured. RESULTS: Shorter leg length was associated with female sex, lower occupational social class and reported hypertension and diabetes. Shorter leg length (lowest quartile) was significantly associated with cognitive impairment but there were no apparent associations with cognitive decline. The association with cognitive impairment was independent of age, sex and education. Social class appeared to be an important mediating factor. CONCLUSIONS: Shorter leg length may be a marker of early life stressors which result in reduced cognitive reserve. Interestingly this association was mediated more strongly by social class (previous occupational status) than by education in this population.     

Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: Differential affective and imaging correlates

Introduction

Subjective cognitive decline (SCD) could indicate preclinical Alzheimer's disease, but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic.

轻度认知功能障碍患者的神经心理学测试

目的探讨轻度认知功能障碍(MCI)患者是否有神经心理方面的损害及损害的特点,以期为早期筛查出MCI患者提供参考指标。方法采用数字颜色连线测验(CTT)、数字广度测试(DS)、词汇流畅性测试(VFT)、中文听觉词汇(CALT)、线段方向判断(JLOT)和Stroop测验对30名MCI患者和30名性别、年龄和教育程度相匹配的正常对照组进行评定。结果MCI患者的CTT、VFT、数字广度倒背和CALT与正常对照组相比差异均有显著性。JLOT、Stroop测验和数字广度顺背成绩虽有所下降,但差异均无显著性。结论MCI患者的神经心理方面有损害。对MCI危险人群进行神经心理学测试能早期筛选出MCI患者。     

轻度认知功能障碍淋巴细胞及炎症蛋白检测

目的探讨MCI认知功能与淋巴细胞及炎症蛋白的关系。方法研究阿尔茨海默病（AD,36例）、轻度认知障碍（MCI,34例）及认知功能正常老年人（认知正常组,36人）的外周血淋巴细胞亚群、免疫球蛋白及炎性蛋白的差异。结果认知正常组、MCI组与AD患者的免疫球蛋白G（IgG）浓度中位数依次为10.5g/L、10.6g/L、13.1g/L（χ2=14.28,P〈0.01）;辅助性T淋巴细胞（TH）比例的中位数依次为41%、35%、37%（χ2=9.96,P〈0.01）;三组间差异有统计学意义。其中认知正常组与MCI组的IgG差异无统计学意义（Z=0.64,P=0.52）,而AD组IgG水平高于MCI组（Z=3.26,P〈0.01）和认知正常组（Z=3.22,P〈0.01）;认知正常组TH高于AD组（Z=2.55,P〈0.05）和MCI组（Z=2.95,P〈0.01）,而MCI组与AD组的TH差异无统计学意义（Z=0.18,P=0.86）。结论 IgG可能在AD与MCI、认知功能正常者的鉴别方面具有重要意义;TH水平降低可能是认知功能受损的标志。     

老年认知功能损害的脑诱发电位研究

目的：探讨阿尔茨海默病（AD）和老年轻度认知功能损害（MCI）的脑诱发电位（BEPs）变化。方法：用美国Nicolet Spirit脑电生理仪记录24例AD病人（AD组）和23例MCI患者（MCI组）的脑干听觉反应（ABR）、关联性负变（CNV）、P300和视觉诱发电位（VEP），并与29名认知功能正常的老年人（NC组）进行比较。结果：（1）3组间大部分的BEPs检测指标的差异有显著性，AD组与NC组之间差异有显著性的指标比AD组与MCI组之间要多；（2）MCI与NC组相比，MCI组的ABR波V绝对波幅和P300的P3靶波幅显著降低；（3）多元逐步判别分析，ABR波Ⅲ绝对潜伏期及绝对波幅、波V对波幅及绝对潜伏期、CNV的反应时间和P300的P3靶波幅具有显著性判别意义，3组的判别总正确率为84.2%。结论：多项BEPs检测有助于AD的诊断，ABR的波V绝对波幅和P300的P3靶波幅显著降低具有早期诊断价值。     

Prospective memory and subjective memory decline: A neuropsychological indicator of memory difficulties in community-dwelling older people

Introduction: Prospective memory difficulties are known to occur in Alzheimer’s disease, and may provide an early indicator of cognitive decline. Older people reporting high levels of subjective memory decline (SMD) but without evidence of cognitive decline on standard neuropsychological tests are increasingly considered at increased risk for Alzheimer’s disease. Therefore, the objective of this study was to investigate whether prospective memory performance is differentially impaired in older people reporting high levels of SMD as compared to a control group. Method: A total of 195 community-dwelling older adults (M_age = 73.48 years) were assessed for self-reported complaints of memory decline and allocated to either a group reporting high levels of SMD (SMD, n = 96) or a healthy control group (HC, n = 99). Groups were assessed on neuropsychological tests, an experimental prospective memory task (focal vs. nonfocal cue conditions), and a naturalistic prospective memory task. Results: The groups did not differ in performance on standard neuropsychological tests of working memory, executive attention, and episodic retrospective memory. Furthermore, on an experimental task of prospective memory (the Supermarket Shopping Trip task), although performance of both groups was better when cues for prospective memory were focal to the ongoing activity (η² = .35), the SMD group were not impaired relative to the control group. On a naturalistic prospective memory task, however, there was a small but significant effect, with the SMD group performing more poorly than the HC group (η² = .02). Conclusions: In older adults with high levels of SMD, naturalistic measures of prospective memory provide an approach to assessing memory performance that can offer a means of investigating the memory complaints of people with SMD. Identifying prospective memory difficulties in SMD also offers a focus for intervention.     

Complexity changes in preclinical Alzheimer’s disease: An MEG study of subjective cognitive decline and mild cognitive impairment

ObjectiveTo analyse magnetoencephalogram (MEG) signals with Lempel-Ziv Complexity (LZC) to identify the regions of the brain showing changes related to cognitive decline and Alzheimeŕs Disease (AD).MethodsLZC was used to study MEG signals in the source space from 99 participants (36 male, 63 female, average age: 71.82 ± 4.06) in three groups (33 subjects per group): healthy (control) older adults, older adults with subjective cognitive decline (SCD), and adults with mild cognitive impairment (MCI). Analyses were performed in broadband (2–45 Hz) and in classic narrow bands (theta (4–8 Hz), alpha (8–12 Hz), low beta (12–20 Hz), high beta (20–30 Hz), and, gamma (30–45 Hz)).ResultsLZC was significantly lower in subjects with MCI than in those with SCD. Moreover, subjects with MCI had significantly lower MEG complexity than controls and SCD subjects in the beta frequency band. Lower complexity was correlated with smaller hippocampal volumes.ConclusionsBrain complexity – measured with LZC – decreases in MCI patients when compared to SCD and healthy controls. This decrease is associated with a decrease in hippocampal volume, a key feature in AD progression.SignificanceThis is the first study to date characterising the changes of brain activity complexity showing the specific spatial pattern of the alterations as well as the morphological correlations throughout preclinical stages of AD.