Multidimensional assessment of time perception along the continuum of Alzheimer's Disease and evidence of alterations in subjective cognitive decline.
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ABSTRACT:
SUBMITTER: Teghil A
PROVIDER: S-EPMC10719320 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
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Multidimensional assessment of time perception along the continuum of Alzheimer's Disease and evidence of alterations in subjective cognitive decline.
Teghil Alice A Boccia Maddalena M Di Vita Antonella A Zazzaro Giulia G Sepe Monti Micaela M Trebbastoni Alessandro A Talarico Giuseppina G Campanelli Alessandra A Bruno Giuseppe G Guariglia Cecilia C de Lena Carlo C D'Antonio Fabrizia F
Scientific reports 20231213 1
Timing alterations occur in Alzheimer's disease (AD), even in early stages (mild cognitive impairment, MCI). Moreover, a stage named subjective cognitive decline (SCD), in which individuals perceive a change in cognitive performance not revealed by neuropsychological tests, has been identified as a preclinical phase of AD. However, no study to date has investigated different dimensions of time processing along the continuum from physiological to pathological aging, and whether timing alterations ...[more]
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Project description:Subjective memory decline is associated with neurodegeneration and increased risk of cognitive decline in participants with no or subjective cognitive impairment, while in patients with mild cognitive impairment or Alzheimer's-type dementia, findings are inconsistent. Our aim was to provide a comprehensive overview of subjective memory decline changes, relative to objective memory performances, and of their relationships with neurodegeneration, across the clinical continuum of Alzheimer's disease. Two hundred participants from the Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce (IMAP+) primary cohort and 731 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) replication cohort were included. They were divided into four clinical groups (Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce/Alzheimer's Disease Neuroimaging Initiative): controls (n = 67/147, age: 60-84/60-90, female: 54/55%), patients with subjective cognitive decline (n = 30/84, age: 54-84/65-80, female: 44/63%), mild cognitive impairment (n = 50/369, age: 58-86/55-88, female: 45/44%) or Alzheimer's-type dementia (n = 36/121, age: 51-86/61-90, female: 41/41%). Subjective and objective memory scores, and their difference (i.e. delta score reflecting memory awareness), were compared between groups. Then, voxelwise relationships between subjective memory decline and neuroimaging measures of neurodegeneration [atrophy (T1-MRI) and hypometabolism (18F-fluorodeoxyglucose-PET)] were assessed across clinical groups and the interactive effect of the level of cognitive impairment within the entire sample was assessed. Analyses were adjusted for age, sex and education, and repeated including only the amyloid-positive participants. In Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce, the level of subjective memory decline was higher in all patient groups (all P < 0.001) relative to controls, but similar between patient groups. In contrast, objective memory deficits progressively worsened from the subjective cognitive decline to the dementia group (all P < 0.001). Accordingly, the delta score showed a progressive decline in memory awareness across clinical groups (all P < 0.001). Voxelwise analyses revealed opposite relationships between the subjective memory decline score and neurodegeneration across the clinical continuum. In the earliest stages (i.e. patients with subjective cognitive decline or Mini Mental State Examination > 28), greater subjective memory decline was associated with increased neurodegeneration, while in later stages (i.e. patients with mild cognitive impairment, dementia or Mini Mental State Examination < 27) a lower score was related to more neurodegeneration. Similar findings were recovered in the Alzheimer's Disease Neuroimaging Initiative replication cohort, with slight differences according to the clinical group, and in the amyloid-positive subsamples. Altogether, our findings suggest that the subjective memory decline score should be interpreted differently from normal cognition to dementia. Higher scores might reflect greater neurodegeneration in earliest stages, while in more advanced stages lower scores might reflect decreased memory awareness, i.e. more anosognosia associated with advanced neurodegeneration.
| S-EPMC8421692 | biostudies-literature
Project description:Subjective cognitive decline (SCD) is a subclinical cognitive impairment that is complained by the individual without being objectively supported at clinical, diagnostic, and neuropsychological levels. It can negatively impact on patient's frailty and quality of life, as well as on the caregiver's burden. Moreover, it can be prodromal to Mild Cognitive Impairment or dementia. Although the clinical manifestations of SCD can differ along with several cognitive domains, to date there are only screening tools to investigate subjective memory complaints. Thus, the first aim of this paper is to propose a preliminary English and Italian version of a new screening tool called MASCoD (Multidimensional Assessment of Subjective Cognitive Decline); the second aim is to propose its preliminary adoption on a pilot sample. This schedule is a brief test derived from the review of the literature and the clinical experience provided by an experts panelist. From pilot tests, it seems promising as it can help the professional to make differential diagnosis and to predict the risk of developing severe cognitive impairment over time, developing a personalized care path. This screening tool is brief, easily embeddable in usual clinical assessment, and administrable by different professionals. Furthermore, following validation, it will allow to collect manifold cognitive manifestations of SCD, addressing the shortage of previous validated instruments globally assessing cognition affected by this condition.
| S-EPMC9748696 | biostudies-literature
Project description:BackgroundImpairment in daily functioning is a clinical hallmark of dementia. Difficulties with "instrumental activities of daily living" (IADL) seem to increase gradually over the course of Alzheimer's disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD.MethodsIn a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging-Alzheimer's Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized.ResultsThe rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p = .453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = - 0.32 [- 0.55, - 0.09], p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (- 1.06 [- 1.27, - 0.85], p < .001) and nearly two SD units per year in stage 4+ (1.93 [- 2.19, - 1.67], p < .001). Overall, results were similar between community-based and memory clinic study cohorts.ConclusionsOur results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.
| S-EPMC7597034 | biostudies-literature
Project description:Objective: The aim of this study was to analyze quantitative sleep changes and their implication on subjective cognitive decline (SCD). Objective sleep patterns were investigated by an actigraph and recorded at the baseline and 2-year after in order to examine specific sleep alterations in SCD. Background: Sleep disorders are very common among average elderly adults and an altered sleep pattern is known to be a risk factor for future development of mild cognitive impairment (MCI) and dementia. Recent studies have shown how sleep is objectively altered in average senior adults with SCD, without any other significant change in cognition and behavior or brain structure. Considering that both SCD and disrupted sleep are risk factors for future MCI and dementia, with sleep only as a modifiable risk factor, further research is required to deeply investigate the interaction between sleep and SCD. Methods: Among 70 community-dwelling elderly individuals who had been enrolled at baseline, 35 (64.6 ± 5.6 years, 15 M/20 F) underwent a complete neuropsychological battery and 1-week wrist actigraphy recording 2 years later during the follow-up stage. Individuals were divided into two groups according to their SCD Questionnaire (SCD-Q) score. Sleep hours, sleep efficiency and onset latency, napping and time awake after sleep onset (WASO) were collected. All individuals underwent structural magnetic resonance imaging (MRI) examination to exclude brain disorders. Data collection was performed at baseline and after 2 years at the follow-up phase. Results: A significantly different night sleep time between the two groups was observed: SCD showed a lower total sleep time (TST) than non-SCD subjects. Moreover, a total time spent in bed (TIB) was significantly lower in SCD subjects over 2 years of observation. Conclusions: Objective changes over time of the sleep pattern, specifically TIB and TST, are present in SCD individuals. The results of the study show that sleep alterations are common in SCD and underline the clinical importance of screening in order to assess sleep alterations as well as improve sleep in average adults with SCD complaints.
| S-EPMC6614445 | biostudies-literature
Project description:Subjective cognitive decline (SCD) is regarded as the first clinical manifestation in the Alzheimer's disease (AD) continuum. Investigating populations with SCD is important for understanding the early pathological mechanisms of AD and identifying SCD-related biomarkers, which are critical for the early detection of AD. With the advent of advanced neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), accumulating evidence has revealed structural and functional brain alterations related to the symptoms of SCD. In this review, we summarize the main imaging features and key findings regarding SCD related to AD, from local and regional data to connectivity-based imaging measures, with the aim of delineating a multimodal imaging signature of SCD due to AD. Additionally, the interaction of SCD with other risk factors for dementia due to AD, such as age and the Apolipoprotein E (ApoE) ɛ4 status, has also been described. Finally, the possible explanations for the inconsistent and heterogeneous neuroimaging findings observed in individuals with SCD are discussed, along with future directions. Overall, the literature reveals a preferential vulnerability of AD signature regions in SCD in the context of AD, supporting the notion that individuals with SCD share a similar pattern of brain alterations with patients with mild cognitive impairment (MCI) and dementia due to AD. We conclude that these neuroimaging techniques, particularly multimodal neuroimaging techniques, have great potential for identifying the underlying pathological alterations associated with SCD. More longitudinal studies with larger sample sizes combined with more advanced imaging modeling approaches such as artificial intelligence are still warranted to establish their clinical utility.
| S-EPMC7507636 | biostudies-literature
Project description:BackgroundIndividuals with subjective cognitive decline (SCD) are at risk of developing Alzheimer's Disease (AD). Traditional seed-based analysis has shown biased functional connectivity (FC) in SCD individuals. To investigate unbiased altered FC by the brain-wide association study (BWAS) and to determine its association with cognition in SCD individuals.MethodsMeasure of association (MA) analysis was applied to detect significant voxels with FC changes. Based on these changes, we identified regions of interest (ROIs) and conducted ROI-wise FC analyses. Correlation analyses were then performed between these FC circuits and cognition.ResultsMA analysis identified 10 ROIs with significantly altered voxels. ROI-wise FC analyses revealed 14 strengthened FC, predominantly parietal-occipital link alterations. The FC between the right superior occipital gyrus and the right postcentral gyrus correlated positively with executive function, while the FC between the right middle occipital gyrus and the left angular gyrus correlated positively with episodic memory in SCD individuals.ConclusionSCD involves multifocal impairments, of which regions of default mode network (DMN) and occipital lobe should be specially focused. Cross-hemispheric alterations indicate an internal interactive impairment pattern in SCD. The reduced FC between the right superior occipital gyrus and the right postcentral gyrus, and between the right middle occipital gyrus and the left angular gyrus, which correlate with specific cognitive functions, could serve as potential biomarkers for SCD diagnosis.
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Project description:Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients.
| S-EPMC10743700 | biostudies-literature
Project description:Purpose: To investigate the dynamic functional connectivity (DFC) and static parameters of graph theory in individuals with subjective cognitive decline (SCD) and the associations of DFC and topological properties with cognitive performance. Methods: Thirty-three control subjects and 32 SCD individuals were enrolled in this study, and neuropsychological evaluations and resting-state functional magnetic resonance imaging scanning were performed. Thirty-three components were selected by group independent component analysis to construct 7 functional networks. Based on the sliding window approach and k-means clustering, distinct DFC states were identified. We calculated the temporal properties of fractional windows in each state, the mean dwell time in each state, and the number of transitions between each pair of DFC states. The global and local static parameters were assessed by graph theory analysis. The differences in DFC and topological metrics, and the associations of the altered neuroimaging measures with cognitive performance were assessed. Results: The whole cohort demonstrated 4 distinct connectivity states. Compared to the control group, the SCD group showed increased fractional windows and an increased mean dwell time in state 4, characterized by hypoconnectivity both within and between networks. The SCD group also showed decreased fractional windows and a decreased mean dwell time in state 2, dominated by hyperconnectivity within and between the auditory, visual and somatomotor networks. The number of transitions between state 1 and state 2, between state 2 and state 3, and between state 2 and state 4 was significantly reduced in the SCD group compared to the control group. No significant differences in global or local topological metrics were observed. The altered DFC properties showed significant correlations with cognitive performance. Conclusion: Our findings indicated DFC network reconfiguration in the SCD stage, which may underlie the early cognitive decline in SCD subjects and serve as sensitive neuroimaging biomarkers for the preclinical detection of individuals with incipient Alzheimer's disease.
| S-EPMC7886811 | biostudies-literature
Project description:Subjective cognitive decline (SCD) is considered to be the preclinical stage of Alzheimer's disease (AD) and has the potential for the early diagnosis and intervention of AD. It was implicated that CSF-tau, which increases very early in the disease process in AD, has a high sensitivity and specificity to differentiate AD from normal aging, and the highly connected brain regions behaved more tau burden in patients with AD. Thus, a highly connected state measured by dynamic functional connectivity may serve as the early changes of AD. In this study, forty-five normal controls (NC), thirty-six individuals with SCD, and thirty-five patients with AD were enrolled to obtain the resting-state functional magnetic resonance imaging scanning. Sliding windows, Pearson correlation, and clustering analysis were combined to investigate the different levels of information transformation states. Three states, namely, the low state, the middle state, and the high state, were characterized based on the strength of functional connectivity between each pair of brain regions. For the global dynamic functional connectivity analysis, statistically significant differences were found among groups in the three states, and the functional connectivity in the middle state was positively correlated with cognitive scales. Furthermore, the whole brain was parcellated into four networks, namely, default mode network (DMN), cognitive control network (CCN), sensorimotor network (SMN), and occipital-cerebellum network (OCN). For the local network analysis, statistically significant differences in CCN for low state and SMN for middle state and high state were found in normal controls and patients with AD. Meanwhile, the differences were also found in normal controls and individuals with SCD. In addition, the functional connectivity in SMN for high state was positively correlated with cognitive scales. Converging results showed the changes in dynamic functional states in individuals with SCD and patients with AD. In addition, the changes were mainly in the high strength of the functional connectivity state.
| S-EPMC9108158 | biostudies-literature
Project description:INTRODUCTION:In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. METHODS:Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. RESULTS:In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ?4 (1.8 [1.3-2.5]) increased the risk of dementia. DISCUSSION:SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.
| S-EPMC6465066 | biostudies-literature