| 1. |
- Olofsson, Jonas K, 1965-, et al.
(författare)
-
Odor identification impairment in carriers of ApoE-ε4 is independent of clinical dementia
- 2010
-
Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 31:4, s. 567-577
-
Tidskriftsartikel (refereegranskat)abstract
- The ApoE gene is expressed in olfactory brain structures and is believed to play a role in neuronal regenerative processes as well as in development of Alzheimer's disease (AD), the most common form of dementia. The ε4 allele has been reported to be associated with compromised odor identification ability in the elderly, and this deficit has been interpreted as a sign of pre-diagnostic AD. However, because it has not been demonstrated that the relationship between the ε4 allele and odor identification is mediated by dementia, it is possible that the ε4 allele may have an effect on odor identification over and above any effects of dementia. The present study investigated effects of ApoE-status on odor identification in a large, population-based sample (n = 1236) of adults (45–80 years), who were assessed for dementia at time of testing and 5 years later. The results showed that the ε4 allele was associated with an odor identification deficit among elderly participants (75–80). Critically, this effect remained after current and pre-diagnostic dementia, vocabulary, global cognitive status and health variables were partialled out. The present results suggest that the ApoE gene plays a role in olfactory functioning that is independent of dementia conversion within 5 years.
|
|
| 2. |
- Nilsson, Lars-Göran, 1944-, et al.
(författare)
-
Challenging the notion of an early-onset of cognitive decline.
- 2009
-
Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 30:4, s. 521-524; discussion 530
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Salthouse claims that cognitive aging starts around 20 years of age. The basis for this claim is cross-sectional data. He dismisses longitudinal data, which typically show the cognitive decline to start much later, around 60 years of age. He states that longitudinal data cannot be trusted because they are flawed. There is a confounding between the effects of maturation and retest effects. We challenge Salthouse's strong claim on four accounts.
|
|
| 3. |
- Persson, Jonas, et al.
(författare)
-
Longitudinal assessment of default-mode brain function in aging
- 2014
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:9, s. 2107-2117
-
Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.
|
|
| 4. |
- Pudas, Sara, et al.
(författare)
-
Midlife memory ability accounts for brain activity differences in healthy aging
- 2014
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:11, s. 2495-2503
-
Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex functions underlie individual differences in memory ability in older individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, we investigated the relative influences of midlife memory ability and age-related memory change on memory-related BOLD-signal variability at one time point, using a sample from a longitudinal population-based aging study (N = 203, aged 55–80 years). Hierarchical regression analyses showed that midlife memory ability, assessed 15–20 years earlier, explained at least as much variance as memory change in clusters in the left inferior prefrontal cortex and the bilateral hippocampus, during memory encoding. Furthermore, memory change estimates demonstrated higher sensitivity than current memory levels in identifying distinct frontal regions where activity was selectively related to age-related memory change, as opposed to midlife memory. These findings highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data and also demonstrate the improved sensitivity of longitudinal measures.
|
|
| 5. |
- Rademakers, R, et al.
(författare)
-
Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.
- 2005
-
Ingår i: Neurobiology of Aging. - New York : Elsevier BV. - 0197-4580 .- 1558-1497. ; 26:8, s. 1145-1151
-
Tidskriftsartikel (refereegranskat)abstract
- Malfunctioning of cyclin-dependent kinase 5 (CDK5) through aberrant proteolytic cleavage of its neuronal activators p35 and p39 is involved in neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative brain diseases. By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients. We performed an association study with five informative SNPs in CDK5 in two independent samples of early-onset AD patients and matched control individuals from The Netherlands and northern Sweden. Association was observed with g.149800G>C in intron 5 of CDK5, and a two times increased risk was observed in both patient samples for carriers of the C-allele. Our data are indicative for a role of the CDK5 molecular complex in the genetic etiology of early-onset AD, and suggest that a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset AD.
|
|
| 6. |
- Varrone, Andrea, et al.
(författare)
-
Positron emission tomography imaging of 5-hydroxytryptamine(1B) receptors in Parkinson's disease
- 2014
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:4, s. 867-875
-
Tidskriftsartikel (refereegranskat)abstract
- Impairment of the central serotonin system in Parkinson's disease (PD) has been shown postmortem and in vivo with positron emission tomography (PET). The aim of this PET study was to examine and compare the availability of the 5-hydroxytryptamine (5-HT)(1B)-receptor subtype in patients with PD and age-matched control subjects. Twelve control subjects and 12 PD patients were examined with PET using the 5-HT1B-radioligand [C-11]AZ10419369. In PD patients, 5-HT1B-receptor availability in the right orbitofrontal cortex was lower than in control subjects. A statistically significant negative correlation between 5-HT1B-receptor availability and age was obtained for the right temporal cortex in control subjects and for the right midbrain and left parahippocampal gyrus in PD patients. The lower regional 5-HT1B-receptor availability is in line with previous studies showing a decrease of serotonin imaging markers in PD and corroborates a role of the serotonin system in the pathophysiology of PD. The demonstrated age effect on 5-HT1B receptors suggest a physiologic and PD-related decline of serotonin function, indicating the importance of controlling for age in clinical studies.
|
|
| 7. |
- Wikgren, Mikael, 1981-, et al.
(författare)
-
APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
- 2012
-
Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:2, s. 335-344
-
Tidskriftsartikel (refereegranskat)abstract
- Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41–81 yr. The authors found that ε4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among ε4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among ε4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among ε3/ε3 carriers. In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
|
|
| 8. |
- Söderlund, Hedvig, et al.
(författare)
-
Cerebral changes on MRI and cognitive function: The CASCADE Study.
- 2006
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 27:1, s. 16-23
-
Tidskriftsartikel (refereegranskat)abstract
- The aging, non-demented brain undergoes several physiological changes, some of which may and some of which may not affect cognitive function. The goal of the present study was to examine the effects of subcortical and periventricular white matter hyperintensities (WMHs), and cortical and subcortical atrophy on cognitive function (episodic and semantic memory, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, CASCADE (Cardiovascular Determinants of Dementia), in which Magnetic Resonance Imaging (MRI) was performed on community-dwelling individuals. The study includes 1,254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4 + 3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WHMS predicted lower performance in motor speed and Stroop (errors). The findings are consistent with findings from lesion and functional neuroimaging studies.
|
|
