Depressed individuals are twice as likely to develop Alzheimer’s disease (AD) as compared to cont... more Depressed individuals are twice as likely to develop Alzheimer’s disease (AD) as compared to controls. Brain amyloid-β (Aβ) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aβ dynamics and depression. The aim of this study was to test if plasma Aβ levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-β1-40 (Aβ40) and amyloid-β1-42 (Aβ42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the Aβ42/Aβ40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, Aβ42/Aβ40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression sev...
ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy r... more ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline. Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin. For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and w...
Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise bio... more Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between the two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-β42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-β40, total...
Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thou... more Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer's disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in ...
Delayed recall of the first words of a list-the primacy position-is thought to be particularly de... more Delayed recall of the first words of a list-the primacy position-is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI). We investigated serial position performance in 88 subjects with aMCI using a 16-word list (the California Verbal Learning Test [CVLT]). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes. After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or del...
Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of o... more Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of order of recall in neuropsychological free recall tests. These are the position on the study list of the first recalled item, and the degree of variability in the order in which items are reported at test (i.e., the temporal distance across the first four recalled items). We tested two hypotheses in separate experiments: 1) whether these measures predicted generalized cognitive ability, and 2) whether they predicted gray matter hippocampal volume. To test hypothesis 1, we conducted ordinal regression analyses on data from a group of 452 participants, aged 60 or above. Memory performance was measured with Rey's AVLT and generalized cognitive ability was measured with the MMSE test. To test hypothesis 2, we conducted a linear regression analysis on data from a sample of 79 cognitively intact individuals aged 60 or over. Memory was measured with the BSRT and hippocampal volume was extrac...
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2015
IntroductionVolumes of hippocampus and cholinergic basal forebrain are associated with delayed re... more IntroductionVolumes of hippocampus and cholinergic basal forebrain are associated with delayed recall performance and may modulate the effect of a muscarinic receptor antagonist on delayed recall in healthy volunteers.MethodsWe studied 15 older adults before and after the oral administration of a single dose of 1 or 2 mg of the preferential M1 muscarinic receptor antagonist trihexyphenidyl (Artane™) or placebo in a double‐blind randomized cross‐over design. Hippocampus and basal forebrain volumes were measured using magnetic resonance imaging.ResultsWe found a significant interaction between treatment and hippocampus volume and a trend level effect between treatment and anterior basal forebrain volume on task performance, with an attenuation of the association between volume size and performance with trihexyphenidyl.DiscussionThese findings suggest a reduction of delayed recall performance with increasing doses of the muscarinic antagonist that is related to an uncoupling of the ass...
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2015
BackgroundPrimacy performance in recall has been shown to predict cognitive decline in cognitivel... more BackgroundPrimacy performance in recall has been shown to predict cognitive decline in cognitively intact elderly and conversion from mild cognitive impairment to Alzheimer's disease (AD). Delayed primacy performance, but not delayed nonprimacy performance, has been shown to be associated with hippocampal volume in cognitively intact older individuals. Because presence of neurofibrillary tangles is an early sign of AD‐related pathology, we set out to test whether cerebrospinal fluid (CSF) levels of tau had an effect on delayed primacy performance, while controlling for hippocampal volume and CSF amyloid‐β 1‐42 levels.MethodsForty‐seven individuals, aged 60 years or older and cognitively intact, underwent a multisession study including lumbar puncture, a magnetic resonance imaging (MRI) scan of the head, and memory testing.ResultsOur regression analyses show that CSF levels of hyperphosphorylated (P) tau are only associated with reduced delayed primacy performance when hippocampa...
Depressed individuals are twice as likely to develop Alzheimer’s disease (AD) as compared to cont... more Depressed individuals are twice as likely to develop Alzheimer’s disease (AD) as compared to controls. Brain amyloid-β (Aβ) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aβ dynamics and depression. The aim of this study was to test if plasma Aβ levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-β1-40 (Aβ40) and amyloid-β1-42 (Aβ42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the Aβ42/Aβ40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, Aβ42/Aβ40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression sev...
ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy r... more ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline. Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin. For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and w...
Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise bio... more Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between the two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-β42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-β40, total...
Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thou... more Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer's disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in ...
Delayed recall of the first words of a list-the primacy position-is thought to be particularly de... more Delayed recall of the first words of a list-the primacy position-is thought to be particularly dependent on intact memory consolidation. Hippocampal volume has been suggested as the primary neuronal correlate of delayed primacy recall in cognitively normal elderly individuals. Here, we studied the association of hippocampal volume with primacy recall in individuals with amnestic mild cognitive impairment (aMCI). We investigated serial position performance in 88 subjects with aMCI using a 16-word list (the California Verbal Learning Test [CVLT]). Primacy and recency performance were measured during learning and delayed recall. Hippocampal volumes were automatically determined from structural MRI scans. We conducted regression analyses with bilateral hippocampal volumes as predictors and serial position indices as outcomes. After controlling for age, gender, and total intracranial volume, bilateral hippocampal volume was not associated with primacy recall either during learning or del...
Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of o... more Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of order of recall in neuropsychological free recall tests. These are the position on the study list of the first recalled item, and the degree of variability in the order in which items are reported at test (i.e., the temporal distance across the first four recalled items). We tested two hypotheses in separate experiments: 1) whether these measures predicted generalized cognitive ability, and 2) whether they predicted gray matter hippocampal volume. To test hypothesis 1, we conducted ordinal regression analyses on data from a group of 452 participants, aged 60 or above. Memory performance was measured with Rey's AVLT and generalized cognitive ability was measured with the MMSE test. To test hypothesis 2, we conducted a linear regression analysis on data from a sample of 79 cognitively intact individuals aged 60 or over. Memory was measured with the BSRT and hippocampal volume was extrac...
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2015
IntroductionVolumes of hippocampus and cholinergic basal forebrain are associated with delayed re... more IntroductionVolumes of hippocampus and cholinergic basal forebrain are associated with delayed recall performance and may modulate the effect of a muscarinic receptor antagonist on delayed recall in healthy volunteers.MethodsWe studied 15 older adults before and after the oral administration of a single dose of 1 or 2 mg of the preferential M1 muscarinic receptor antagonist trihexyphenidyl (Artane™) or placebo in a double‐blind randomized cross‐over design. Hippocampus and basal forebrain volumes were measured using magnetic resonance imaging.ResultsWe found a significant interaction between treatment and hippocampus volume and a trend level effect between treatment and anterior basal forebrain volume on task performance, with an attenuation of the association between volume size and performance with trihexyphenidyl.DiscussionThese findings suggest a reduction of delayed recall performance with increasing doses of the muscarinic antagonist that is related to an uncoupling of the ass...
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2015
BackgroundPrimacy performance in recall has been shown to predict cognitive decline in cognitivel... more BackgroundPrimacy performance in recall has been shown to predict cognitive decline in cognitively intact elderly and conversion from mild cognitive impairment to Alzheimer's disease (AD). Delayed primacy performance, but not delayed nonprimacy performance, has been shown to be associated with hippocampal volume in cognitively intact older individuals. Because presence of neurofibrillary tangles is an early sign of AD‐related pathology, we set out to test whether cerebrospinal fluid (CSF) levels of tau had an effect on delayed primacy performance, while controlling for hippocampal volume and CSF amyloid‐β 1‐42 levels.MethodsForty‐seven individuals, aged 60 years or older and cognitively intact, underwent a multisession study including lumbar puncture, a magnetic resonance imaging (MRI) scan of the head, and memory testing.ResultsOur regression analyses show that CSF levels of hyperphosphorylated (P) tau are only associated with reduced delayed primacy performance when hippocampa...
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