To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and ...controls.
We included 64 patients with AD (67 +/- 9 years; F/M 38/26), 44 patients with MCI (71 +/- 6 years; 21/23), and 34 controls (67 +/- 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 +/- 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools.
All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio HR: 5.7 95% confidence interval: 1.5-22.2), hippocampal atrophy rate (5.2 1.9-14.3), and whole brain atrophy rate (2.8 1.1-7.2) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1-606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression.
Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD.
In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of ...lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression.
After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016).
Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.
Epidemiology and risk factors of dementia van der Flier, W M; Scheltens, P
Journal of neurology, neurosurgery and psychiatry,
12/2005, Letnik:
76, Številka:
suppl 5
Journal Article
Recenzirano
Odprti dostop
...epidemiological studies often focus on dementia as a whole, sometimes giving separate numbers for the two most important subtypes-AD and VaD. ...the conflicting reports with respect to the effect ...of blood pressure on the development of dementia may be entirely explained by the moment of measuring the risk factor. Risk factors for dementia include age and the female sex, especially at high age. ...genetic factors (APOE epsilon4) and vascular risk factors play an important role.
Abstract Alzheimer’s disease (AD) is the most common form of dementia, affecting millions of people worldwide. One of the prominent causative factors of AD pathogenesis is cerebral vascular ...dysfunction, which results in diminished cerebral perfusion. Moreover, due to the loss of the protective function of the blood-brain barrier (BBB), impaired clearance of excess neurotoxic amyloid beta (Aβ) occurs, causing vascular perturbation and diminished cognitive functioning. The relationship between the prevalence of AD and vascular risk factors is complex and not fully understood. In this review we illustrate the vascular risk factors, their effects on BBB function and their contributions to the onset of AD. Additionally, we discuss the underlying factors that may lead to altered neurovascular function and/or cerebral hypoperfusion in AD.
The relation between pathology and cognitive dysfunction in dementia is still poorly understood, although disturbed communication between different brain regions is almost certainly involved. In this ...study we combine magneto-encephalography (MEG) and network analysis to investigate the role of functional sub-networks (modules) in the brain with regard to cognitive failure in Alzheimer's disease. Whole-head resting-state (MEG) was performed in 18 Alzheimer patients (age 67±9, 6 females, MMSE 23±5) and 18 healthy controls (age 66±9, 11 females, MMSE 29±1). We constructed functional brain networks based on interregional synchronization measurements, and performed graph theoretical analysis with a focus on modular organization. The overall modular strength and the number of modules changed significantly in Alzheimer patients. The parietal cortex was the most highly connected network area, but showed the strongest intramodular losses. Nonetheless, weakening of intermodular connectivity was even more outspoken, and more strongly related to cognitive impairment. The results of this study demonstrate that particularly the loss of communication between different functional brain regions reflects cognitive decline in Alzheimer's disease. These findings imply the relevance of regarding dementia as a functional network disorder.
► Network analysis applied to MEG data to study functional sub-networks (modules). ► In Alzheimer's disease, altered modular organization relates to cognitive symptoms. ► Intermodular connectivity is damaged most, parietal region has highest local damage.
Highlights • MEG activity in AD is slower, more regular, less complex and less well organized compared to healthy controls. • Posterior and temporal areas are the most affected regions. • MEG has ...currently not been used to its full potential.
Cognitive reserve (CR) is thought to protect against the consequence of age- or disease-related structural brain changes across multiple cognitive domains. The neural basis of CR may therefore ...comprise a functional network that is actively involved in many different cognitive processes. To investigate the existence of such a “task-invariant” CR network, we measured functional connectivity in a cognitively normal sample between 20 and 80 years old (N = 265), both at rest and during the performance of 11 separate tasks that aim to capture four latent cognitive abilities (i.e. vocabulary, episodic memory, processing speed, and fluid reasoning). For each individual, we determined the change in functional connectivity from the resting state to each task state, which is referred to as “task potency” (Chauvin et al., 2018, 2019). Task potency was calculated for each pair among 264 nodes (Power et al., 2012) and then summarized across tasks reflecting the same cognitive ability. Subsequently, we established the correlation between task potency and IQ or education (i.e. CR factors). We identified a set of 57 pairs in which task potency showed significant correlations with IQ, but not education, across all four cognitive abilities. These pairs were included in a principal component analysis, from which we extracted the first component to obtain a latent variable reflecting task potency in this task-invariant CR network. This task potency variable was associated with better episodic memory (β = 0.19, p < .01) and fluid reasoning performance (β = 0.17, p < .01) above and beyond the effects of cortical thickness (range absolute β = 0.28-0.32, p < .001). Our identification of this task-invariant network contributes to a better understanding of the mechanism underlying CR, which may facilitate the development of CR-enhancing treatments. Our work also offers a useful alternative operational measure of CR for future studies.
•Cognitive reserve (CR) protects cognition in the face of structural brain changes.•We studied the neural basis of CR in healthy individuals across the adult age span.•We identified a generic, “task-invariant” functional network underlying CR.•“Task potency” in this network related to IQ across four cognitive abilities.•The CR network predicted cognitive performance above and beyond brain structure.
To determine prevalence and severity of microbleeds (MBs) in a large cohort of patients attending a memory clinic.
The authors consecutively included patients attending their memory clinic between ...January 2002 and April 2005. They analyzed prevalence and number of MBs according to demographic, diagnostic, and MRI data.
The authors included 772 patients (53% men, age 66 +/- 11). One hundred twenty-seven patients (17%) exhibited at least one MB. The prevalence differed according to diagnostic groups (p < 0.0001): Sixty-five percent of patients with vascular dementia exhibited MBs vs 18% of Alzheimer disease patients, 20% of mild cognitive impairment patients, and 10% of patients with subjective complaints. The presence of MBs was associated with age, white matter hyperintensities, lacunar infarcts, and infarcts.
The prevalence of microbleeds (MBs) in a large cohort of patients attending a memory clinic is higher than previously described in community samples and lower than reported in stroke patients. This finding of a relatively high proportion of MBs in Alzheimer disease and mild cognitive impairment provides further evidence for the involvement of vascular factors in neurodegenerative diseases such as Alzheimer disease.
To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study.
In 199 patients with Alzheimer's disease (AD), 10 with ...vascular dementia (VaD), 26 with dementia with Lewy bodies (DLB), 20 with behavioural variant frontotemporal dementia (bvFTD), 15 with language variant frontotemporal dementia (lvFTD) and 112 controls we assessed five cognitive domains: memory, language, attention, executive and visuospatial functioning, and global cognition (Mini-Mental State Examination, MMSE). All subjects had at least two neuropsychological assessments (median 2, range 2-7). Neuropsychological data were standardized into z scores using baseline performance of controls as reference. Linear mixed models (LMMs) were used to estimate baseline cognitive functioning and cognitive decline over time for each group, adjusted for age, gender and education.
At baseline, patients with dementia performed worse than controls in all cognitive domains (p < 0.05) except visuospatial functioning, which was only impaired in patients with AD and DLB (p < 0.001). During follow-up, patients with AD declined in all cognitive domains (p < 0.001). DLB showed decline in every cognitive domain except language and global cognition. bvFTD showed rapid decline in memory, language, attention and executive functioning (all p < 0.01) whereas visuospatial functioning remained fairly stable. lvFTD declined mostly in attention and executive functioning (p < 0.01). VaD showed decline in attention and executive functioning.
We show cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.
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