Sources of cortical rhythms in adults during physiological aging: a multicentric EEG study

This electroencephalographic (EEG) study tested whether cortical EEG rhythms (especially delta and alpha) show a progressive increasing or decreasing trend across physiological aging. To this aim, we analyzed the type of correlation (linear and nonlinear) between cortical EEG rhythms and age. Resting eyes-closed EEG data were recorded in 108 young (Nyoung; age range: 18-50 years, mean age 27.3+/-7.3 SD) and 107 elderly (Nold; age range: 51-85 years, mean age 67.3+/-9.2 SD) subjects. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that delta sources in the occipital area had significantly less magnitude in Nold compared to Nyoung subjects. Similarly, alpha 1 and alpha 2 sources in the parietal, occipital, temporal, and limbic areas had significantly less magnitude in Nold compared to Nyoung subjects. These nine EEG sources were given as input for evaluating the type (linear, exponential, logarithmic, and power) of correlation with age. When subjects were considered as a single group there was a significant linear correlation of age with the magnitude of delta sources in the occipital area and of alpha 1 sources in occipital and limbic areas. The same was true for alpha 2 sources in the parietal, occipital, temporal, and limbic areas. In general, the EEG sources showing significant linear correlation with age also supported a nonlinear correlation with age. These results suggest that the occipital delta and posterior cortical alpha rhythms decrease in magnitude during physiological aging with both linear and nonlinear trends. In conclusion, this new methodological approach holds promise for the prediction of dementia in mild cognitive impairment by regional source rather than surface EEG data and by both linear and nonlinear predictors.     

Resting state cortical rhythms in mild cognitive impairment and Alzheimer's disease: electroencephalographic evidence

Physiological brain aging is characterized by a combination of synaptic pruning, loss of cortico-cortical connections and neuronal apoptosis that provoke age-dependent decline of cognitive functions. Neural/synaptic redundancy and plastic remodeling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. Unfortunately, in pathological situations, aging triggers neurodegenerative processes that impact on cognition, like Alzheimer's disease (AD). Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including digital electroencephalography (EEG) allow non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing, and coherence of brain rhythmic oscillations at various frequencies. The present review of field EEG literature suggests that discrimination between physiological and pathological brain aging clearly emerges at the group level, with some promising result on the informative value of EEG markers at the individual level. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost, widely available on the territory and non-invasive screening of at-risk populations.     

Reactivity of cortical alpha rhythms to eye opening in mild cognitive impairment and Alzheimer's disease: an EEG study

Cortical sources of resting eyes-closed alpha rhythms are typically abnormal in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. Here we tested the hypothesis of a progressive impairment of cortical alpha reactivity to eye-opening across amnesic MCI and mild AD subjects, reflecting another aspect of the impairment of cortical neural synchronization. Resting electroencephalography (EEG) data were recorded in 36 normal elderly subjects (Nold), 91 amnesic MCI, and 31 mild AD subjects during eyes-closed and -open conditions. EEG sources were estimated by LORETA software. In the eye-closed condition, posterior alpha 1 (8-10.5 Hz) sources were lower in MCI and AD than Nold subjects. The opposite was true for occipital delta sources (2-4 Hz). Reactivity to the eyes-open condition showed posterior alpha 1 and alpha 2 (10.5-13 Hz) sources was high in the Nold, intermediate in the MCI, and low in the AD subjects. Furthermore, occipital alpha 1 reactivity across MCI and AD subjects was correlated to the cognitive impairment as revealed by Mini-Mental State Examination score. In conclusion, at least at group level, the continuum across amnesic MCI and mild AD status is related to an impaired reactivity of cortical neuronal synchronization to eyes opening at alpha rhythms.     

Fronto-parietal coupling of brain rhythms in mild cognitive impairment: a multicentric EEG study

Electroencephalographic (EEG) data were recorded in 69 normal elderly (Nold), 88 mild cognitive impairment (MCI), and 109 mild Alzheimer's disease (AD) subjects at rest condition, to test whether the fronto-parietal coupling of EEG rhythms is in line with the hypothesis that MCI can be considered as a pre-clinical stage of the disease at group level. Functional coupling was estimated by synchronization likelihood of Laplacian-transformed EEG data at electrode pairs, which accounts for linear and non-linear components of that coupling. Cortical rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). Compared to the Nold subjects, the AD patients presented a marked reduction of the synchronization likelihood (delta to gamma) at both fronto-parietal and inter-hemispherical (delta to beta 2) electrodes. As a main result, alpha 1 synchronization likelihood progressively decreased across Nold, MCI, and mild AD subjects at midline (Fz-Pz) and right (F4-P4) fronto-parietal electrodes. The same was true for the delta synchronization likelihood at right fronto-parietal electrodes (F4-P4). For these EEG bands, the synchronization likelihood correlated with global cognitive status as measured by the Mini Mental State Evaluation. The present results suggest that at group level, fronto-parietal coupling of the delta and alpha rhythms progressively becomes abnormal though MCI and mild AD. Future longitudinal research should evaluate whether the present EEG approach is able to predict the cognitive decline in individual MCI subjects.     

Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study

The authors investigated whether engaging in cognitive activities is associated with aging and mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, MN. A random sample of 1,321 study participants ages 70 to 89 (N=1,124 cognitively normal persons, and N=197 subjects with MCI) were interviewed about the frequency of cognitive activities carried out in late life (within 1 year of the date of interview). Computer activities; craft activities, such as knitting, quilting, etc.; playing games; and reading books were associated with decreased odds of having MCI. Social activities, such as traveling, were marginally significant. Even though the point-estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none of these reached statistical significance. The equally high prevalence of reading newspapers in both groups yielded no significant between-group difference.     

Stability of clinical condition in mild cognitive impairment is related to cortical sources of alpha rhythms: an electroencephalographic study

Previous evidence has shown that resting eyes-closed cortical alpha rhythms are higher in amplitude in mild cognitive impairment (MCI) than Alzheimer's disease (AD) subjects (Babiloni et al. [2006a]: Human Brain Mapp 27:162-172; [2006b]: Clin Neurophysiol 117:252-268; [2006c]: Neuroimage 29:948-964; [2006d]: Ann Neurol 59:323-334; [2006e]: Clin Neurophysiol 117:1113-1129; [2006f]: Neuroimage 31:1650-1665). This study tested the hypothesis that, in amnesic MCI subjects, high amplitude of baseline cortical alpha rhythms is related to long-term stability of global cognition on clinical follow-up. Resting electroencephalographic (EEG) data were recorded in 100 amnesic MCI subjects during eyes-closed condition. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Cortical EEG sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Global cognition was indexed by mini mental state evaluation (MMSE) score at the time of EEG recordings (baseline) and about after 1 year. Based on the MMSE percentage difference between baseline and 1-year follow-up (MMSEvar), the MCI subjects were retrospectively divided into three arbitrary groups: DECREASED (MMSEvar ≤ -4%; N = 43), STABLE (MMSEvar ≈ 0; N = 27), and INCREASED (MMSEvar ≥ +4%; N = 30). Subjects' age, education, individual alpha frequency, gender, and MMSE scores were used as covariates for statistical analysis. Baseline posterior cortical sources of alpha 1 rhythms were higher in amplitude in the STABLE than in the DECREASED and INCREASED groups. These results suggest that preserved resting cortical neural synchronization at alpha frequency is related to a long-term (1 year) stable cognitive function in MCI subjects. Future studies should use serial MMSE measurements to confirm and refine the present results.     

Apolipoprotein E and alpha brain rhythms in mild cognitive impairment: a multicentric electroencephalogram study

OBJECTIVE: Relationships between the apolipoprotein E epsilon4 allele and electroencephalographic (EEG) rhythmicity have been demonstrated in Alzheimer's disease (AD) patients but not in the preclinical stage prodromic to it, namely, mild cognitive impairment (MCI). The present multicentric EEG study tested the hypothesis that presence of epsilon4 affects sources of resting EEG rhythms in both MCI and AD subjects. METHODS: We enrolled 89 MCI subjects (34.8% with epsilon4) and 103 AD patients (50.4% with epsilon4). Resting eyes-closed EEG data were recorded for all subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. RESULTS: Results showed that amplitude of alpha 1 and 2 sources in occipital, temporal, and limbic areas was lower in subjects carrying the epsilon4 allele than in those not carrying the epsilon4 allele (p < 0.01). This was true for both MCI and AD. For the first time to our knowledge, a relationship was shown between ApoE genotype and global neurophysiological phenotype (ie, cortical alpha rhythmicity) in a preclinical AD condition, MCI, in addition to clinically manifest AD. INTERPRETATION: Such a demonstration motivates future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.     

血管性认知障碍不同亚型患者认知功能及MRI检查的对比研究

目的探讨血管性认知障碍各亚型患者之间及其与认知功能正常者之间的认知功能及脑组织影像学表现的差异。方法采用简易智能状态检查量表、认知能力筛查量表和简易智能-认知能力联合检查量表对62例血管性认知障碍患者(无痴呆型血管性认知障碍34例、血管性痴呆18例、混合性痴呆10例)和50例正常对照者的认知功能进行评价,通过磁共振成像分析其容积测量值、脑叶萎缩、皮质下白质疏松和腔隙性脑梗死等影像学参数的差异。结果与对照组比较,血管性认知障碍各亚组患者认知功能评分呈逐步递减趋势(均P<0.05),但血管性痴呆与混合性痴呆患者之间差异无统计学意义(P>0.05)。血管性认知障碍各亚组患者双侧前额角容积、第三脑室容积测量值以及额叶、颞叶、顶叶、枕叶萎缩,皮质下白质疏松和腔隙性脑梗死评分均高于对照组(P<0.05),其影像学异常改变在进展为痴呆后更为明显。混合性痴呆患者的特征性表现为双侧海马容积、内嗅叶皮质容积减小,颞叶萎缩(均P<0.05),但无明显的腔隙性脑梗死(P>0.05)。结论血管性认知障碍患者的影像学异常改变可部分反映不同亚型的病理改变,但对认知障碍程度的反映尚缺乏敏感性,能否联合认知功能评分共同作为血管性认知障碍临床预测指标尚待进一步研究。     

Normal rates of cognitive change in successful aging: the freedom house study.

We determined the rates of cognitive change associated with twenty individual measures. Participants included 547 noninstitutionalized septuagenarians and octogenarian residents of a comprehensive care retirement community who were studied over three years. Latent growth curves (LGC) of multiple cognitive measures were compared to a LGC model of the rates of change in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). All curves were standardized relative to each variable's baseline distribution. Baseline scores were within their expected normal age-specific ranges. Most measures showed significant rates of change over time. There was also significant variability about those rates, suggesting clinical heterogeneity. Many deteriorated over time, as did ADLs and IADLs. However, performance on some measures improved, consistent with learning effects. The rates of change in two measures, the Executive Interview and the Trail Making Test, were closely related to decline in IADLs. These results suggest that age-related cognitive decline is a dynamic longitudinal process affecting multiple cognitive domains. Heterogeneity in the rates of cognitive change may reflect the summed effects of age and comorbid conditions affecting cognition. Some measures may be ill-suited for measuring age-related changes in cognition, either because they are insensitive to change, or hindered by learning effects. Nonverbal measures appear to be particularly well suited for the prediction of age-related functional decline. These observations are relevant to the definition and diagnosis of "dementing" conditions.     

Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study

Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia.     

Leisure activity and risk of cognitive impairment: the Chongqing aging study

The authors followed 5,437 people aged 55 years and older with normal baseline Mini-Mental State Examination score annually for 5 years. The mean incidence of cognitive impairment was 2.3% per year. Cognitive activities in both the individual item (playing board games and reading) and the composite measure were associated with the reduced risk of cognitive impairment, while watching television was associated with an increased risk of cognitive impairment.     

Cognitive training changes hippocampal function in mild cognitive impairment: a pilot study

A randomized pilot experiment examined the neural substrates of response to cognitive training in participants with mild cognitive impairment (MCI). Participants performed exercises previously demonstrated to improve verbal memory and an active control group performed other computer activities. An auditory-verbal fMRI task was conducted before and after the two-month training program. Verbal memory scores improved significantly and left hippocampal activation increased significantly in the experimental group (gains in 5 of 6 participants) relative to the control group (reductions in all 6 participants). Results suggest that the hippocampus in MCI may retain sufficient neuroplasticity to benefit from cognitive training.     

Catatonia causing permanent cognitive impairment: a case study.

OBJECTIVE: We describe a case of psychogenic malignant catatonia resulting in permanent cognitive impairment. BACKGROUND: Catatonia is a neuropsychiatric syndrome characterized by catalepsy, negativism, mutism, muscular rigidity, and mannerisms, often accompanied by autonomic instability and fever. Little is known about the long-term cognitive consequences of the syndrome. METHOD: Medical history includes neurologic examination, neuropsychological evaluation, electroencephalographic data, magnetic resonance imaging, sodium amytal interview, and treatment with electroconvulsive therapy. RESULTS: Selective deficits in executive function and an anterograde amnesia were evident a week post-ECT treatment and continued to be present at follow-up after 2 years and 8 months. CONCLUSION: The permanent cognitive impairments are considered in the context of catatonia as a frontal lobe syndrome.     

Brain function during multi-trial learning in mild cognitive impairment: a PET activation study

We explored functional brain changes with positron emission tomography (PET) in mild cognitive impairment (MCI) patients and elderly normal controls by employing an episodic memory task that included two successive encoding trials of semantically related word-pairs and final retrieval. Both groups demonstrated significant learning across the two trials. The control group showed predominantly left frontal activity during encoding, and right frontal plus left temporal activity during retrieval. However, the MCI patients recruited partly different brain regions. They failed to activate right frontal and left temporal areas during retrieval, and failed to show any different activation for encoding on the first and second trials, whereas the controls activated a region of posterior cingulate. There was indication of compensatory increases in rCBF of the occipital cortex during incremental learning and the left frontal lobe during retrieval in the patients. These results suggest different episodic memory processing in the MCI group, and a possible over-reliance on semantic processing. Subtle functional changes occur in the pre-Alzheimer brain before there are marked structural or behavioural abnormalities.     

Longitudinal change in neuropsychological performance using latent growth models: a study of mild cognitive impairment

The goal of the current study was to examine cognitive change in both healthy controls (n?=?229) and individuals with mild cognitive impairment (MCI) (n?=?397) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We applied latent growth modeling to examine baseline and longitudinal change over 36 months in five cognitive factors derived from the ADNI neuropsychological test battery (memory, executive function/processing speed, language, attention and visuospatial). At baseline, MCI patients demonstrated lower performance on all of the five cognitive factors when compared to controls. Both controls and MCI patients declined on memory over 36 months; however, the MCI patients declined at a significantly faster rate than controls. The MCI patients also declined over 36 months on the remaining four cognitive factors. In contrast, the controls did not exhibit significant change over 36 months on the non-memory cognitive factors. Within the MCI group, executive function declined faster than memory, while the other factor scores changed slower than memory over time. These findings suggest different patterns of cognitive change in healthy older adults and MCI patients. The findings also suggest that, when compared with memory, executive function declines faster than other cognitive factors in patients with MCI. Thus, decline in non-memory domains may be an important feature for distinguishing healthy older adults and persons with MCI.     

Disability and mild cognitive impairment: a longitudinal population-based study.

OBJECTIVE: To determine whether mild cognitive deficit is associated with parallel changes in ability to perform activities of daily living. BACKGROUND: While considerable research has been conducted on the effect of senile dementia and other neurodegenerative disorders on ability to perform everyday activities, little is known about the much larger group of elderly persons suffering from mild cognitive deficits. METHODS: Disability prevalence was estimated in 368 persons over the age of 65 years recruited from the general population via a general practitioner network. Subjects were followed over a 3-year period using computerized cognitive assessment and observations of everyday functioning. Standardized neurological assessment in the third year permitted the identification of subjects who have evolved towards dementia. RESULTS: An overall disability prevalence was found in the general population of 26.3%, with 30.8% in subjects with sub-clinical cognitive impairment. Longitudinal follow-up showed cognitive decline over time without dementia to be paralleled by changes in activity performance, with visuospatial deficits having the most marked effect on overall functioning. High intelligence quotient (IQ) and education are seen to reduce the degree of activity loss, but only when senile dementia is not present. CONCLUSIONS: Difficulties in the performance of everyday activities were found more frequently in non-demented subjects with mild cognitive deficits than in the general population. High pre-morbid levels of ability are seen to have a protective effect. A diagnosis of dementia should not therefore be required by persons with cognitive impairment applying for home help.     

Association between circadian rhythms, sleep and cognitive impairment in healthy older adults: an actigraphic study

There is increasing evidence for the relationship between circadian rhythm disturbance and cognitive decline in the older adult. This study measured circadian activity rhythms in a small group of healthy community-dwelling older adults (n?=?26). Each participant completed a battery of neuropsychological tests and completed sleep diaries and 6?days of actigraphy. Ten participants were identified as having very early signs of cognitive decline as indicated by their performance on the memory tests. Results showed minimal differences on the sleep/activity and circadian parameters across the two groups (declined vs. intact), although there was a significant difference in the acrophase between the declined and intact groups. These findings, although exploratory, suggest that very subtle changes in circadian rhythm may be detected in older adults showing pre-clinical changes in cognitive performance.