| 1. |
- Ekström, Ingrid, et al.
(author)
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Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
- 2017
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In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:6, s. 1238-1243
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Journal article (peer-reviewed)abstract
- ObjectivesTo determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.DesignProspective cohort study.SettingBetula Study, Umeå, Sweden.ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).MeasurementsOlfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.ResultsWithin the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.ConclusionPoor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
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| 2. |
- Larsson, Maria, et al.
(author)
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Loss of Olfactory Function Predicts Mortality Irrespective of Dementia Conversion : 10-year follow-up of an age-varied sample
- 2016
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In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 41:9, s. e111-e288
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Journal article (peer-reviewed)abstract
- The objective of this study was to examine the association between performance in odor identification and future mortality in a community cohort of adults aged between 40 and 90 years. We assessed olfactory performance with a 13-item-version of the Scandinavian Odor Identification Test (SOIT). The results showed that during follow-up (mean=9.4 years, standard deviation=2.23), 411 of 1774 (23.2%) participants died. In a Cox model, the association between higher SOIT score and mortality was highly significant (hazard ratio [HR]=0.74, per point interval, 95% confidence interval [CI]=0.71–0.77, p<0.001). The effect was attenuated, but remained significant after controlling for age, sex, education, and health and cognitive variables that were also associated with an increased risk of mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Controlling for dementia conversion prior to death did not attenuate the association between SOIT score and mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Similar results were obtained for olfactory sensitivity as assessed by self-report. Overall, the present findings show that poor odor identification performance is associated with an increased likelihood of future mortality in middle-aged and older adults, after controlling for social, cognitive, and medical risk factors. Most importantly, controlling for the development of dementia did not attenuate the association between odor identification and mortality, suggesting that olfactory decline might mark deteriorating health also irrespective of dementia.
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| 3. |
- Lind, Johanna, et al.
(author)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Journal article (peer-reviewed)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 4. |
- Lind, Johanna, et al.
(author)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Journal article (peer-reviewed)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 5. |
- Olofsson, Jonas K., et al.
(author)
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Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
- 2016
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In: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 85, s. 1-9
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Journal article (peer-reviewed)abstract
- The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memoryand olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45–90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10–20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.
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| 6. |
- Persson, Jonas, 1971-, et al.
(author)
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Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele : A risk for AD?
- 2006
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 66, s. 1029-1033
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood.METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance.RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe.CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.
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| 7. |
- Persson, Jonas, et al.
(author)
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Altered deactivation in individuals with genetic risk for Alzheimer's disease
- 2008
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In: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 46:6, s. 1679-1687
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Journal article (peer-reviewed)abstract
- Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (APOE4) allele and the common form of Alzheimer’s disease (AD), and altered functional brain activation has been observed in non-demented APOE4 carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented APOE4 carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigatin altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.
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| 8. |
- Stanciu, Ingrid, et al.
(author)
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Olfactory Impairment and Subjective Olfactory Complaints Independently Predict Conversion to Dementia : A Longitudinal, Population-Based Study
- 2014
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In: Journal of the International Neuropsychological Society. - 1355-6177 .- 1469-7661. ; 20:2, s. 209-217
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Journal article (peer-reviewed)abstract
- We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as worse than normal were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion. (JINS, 2014, 20, 1-9)
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| 9. |
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