| 1. |
- Bruno, Davide, et al.
(author)
-
A study on the specificity of the association between hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.
- 2015
-
In: Neuropsychologia. - : Elsevier BV. - 1873-3514 .- 0028-3932. ; 69, s. 1-8
-
Journal article (peer-reviewed)abstract
- Delayed recall at the primacy position (first few items on a list) has been shown to predict cognitive decline in cognitively intact elderly participants, with poorer delayed primacy performance associated with more pronounced generalized cognitive decline during follow-up. We have previously suggested that this association is due to delayed primacy performance indexing memory consolidation, which in turn is thought to depend upon hippocampal function. Here, we test the hypothesis that hippocampal size is associated with delayed primacy performance in cognitively intact elderly individuals. Data were analyzed from a group (N=81) of cognitively intact participants, aged 60 or above. Serial position performance was measured with the Buschke selective reminding test (BSRT). Hippocampal size was automatically measured via MRI, and unbiased voxel-based analyses were also conducted to explore further regional specificity of memory performance. We conducted regression analyses of hippocampus volumes on serial position performance; other predictors included age, family history of Alzheimer's disease (AD), APOE ε4 status, education, and total intracranial volume. Our results collectively suggest that there is a preferential association between hippocampal volume and delayed primacy performance. These findings are consistent with the hypothesis that delayed primacy consolidation is associated with hippocampal size, and shed light on the relationship between delayed primacy performance and generalized cognitive decline in cognitively intact individuals, suggesting that delayed primacy consolidation may serve as a sensitive marker of hippocampal health in these individuals.
|
|
| 2. |
- Bruno, Davide, et al.
(author)
-
Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants.
- 2012
-
In: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 47:5, s. 347-52
-
Journal article (peer-reviewed)abstract
- Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE ε4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE ε4. Our results show that the presence of APOE ε4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ε4 have higher CSF NFL levels than non-ε4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of ε4.
|
|
| 3. |
- Bruno, Davide, et al.
(author)
-
The recency ratio is associated with reduced CSF glutamate in late-life depression.
- 2017
-
In: Neurobiology of learning and memory. - : Elsevier BV. - 1095-9564 .- 1074-7427. ; 141, s. 14-18
-
Journal article (peer-reviewed)abstract
- 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 individuals with late-life MDD. For comparison, glutamine or GABA were not correlated with any memory performance measure.
|
|
| 4. |
- Bruno, Davide, et al.
(author)
-
The relationship between CSF tau markers, hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.
- 2015
-
In: Alzheimer's & dementia : diagnosis, assessment & disease monitoring. - : Wiley. - 2352-8729. ; 1:1, s. 81-86
-
Journal article (peer-reviewed)abstract
- Primacy performance in recall has been shown to predict cognitive decline in cognitively intact elderly, and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Delayed primacy performance, but not delayed non-primacy performance, has been shown to be associated with hippocampal volume in cognitively intact older individuals. Since 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 Aβ 1-42 levels.
|
|
| 5. |
- Pillai, Anilkumar, et al.
(author)
-
Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder.
- 2019
-
In: Biomarkers in neuropsychiatry. - : Elsevier BV. - 2666-1446. ; 1
-
Journal article (peer-reviewed)abstract
- Late-life major depression (LLMD) is a risk factor for the development of mild cognitive impairment and dementia, including Alzheimer's disease (AD) and vascular dementia. Immune dysregulation and changes in innate immune responses in particular, have been implicated in the pathophysiology of both LLMD and AD. Complement system, a key component of the innate immune mechanism, is known to play an important role in synaptic plasticity and cognitive functions. However, its role in LLMD remains unknown. In the present study, we examined the levels of complement component 3 (C3, the convergence point of all complement activation pathways) in the cerebrospinal fluid (CSF) of elderly depressed subjects compared to healthy controls; as well as the relationship of CSF C3 levels with amyloid-beta (Aβ42 and Aβ40), total tau (T-tau) and phosphorylated tau (P-tau) proteins and cognition scores. CSF was obtained from 50 cognitively intact volunteers (major depression group, N = 30; comparison group, N = 20) and analyzed for levels of C3 by ELISA. C3 levels were marginally lower in the major depression group relative to the comparison group. We did not find any significant association of C3 with the AD biomarkers Aβ42 reflecting plaque pathology, P-tau related to tau pathology or the neurodegeneration biomarker T-tau. In contrast, C3 was positively correlated with CSF Aβ40, which may reflect Aβ deposition in cerebral vessel walls. We observed a negative correlation between C3 levels and Total Recall on the Buschke Selective Reminding Test (BSRT) for memory performance in the depressed subjects when controlling for education. This initial evidence on C3 status in LLMD subjects may have implications for our understanding of the pathophysiology of major depression especially in late life.
|
|
| 6. |
- Pomara, Nunzio, et al.
(author)
-
Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder.
- 2012
-
In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 169:5, s. 523-30
-
Journal article (peer-reviewed)abstract
- Major depressive disorder is common in the elderly, and symptoms are often not responsive to conventional antidepressant treatment, especially in the long term. Soluble oligomeric and aggregated forms of amyloid beta peptides, especially amyloid beta 42, impair neuronal and synaptic function. Amyloid beta 42 is the main component of plaques and is implicated in Alzheimer's disease. Amyloid beta peptides also induce a depressive state in rodents and disrupt major neurotransmitter systems linked to depression. The authors assessed whether major depression was associated with CSF levels of amyloid beta, tau protein, and F2-isoprostanes in elderly individuals with major depressive disorder and age-matched nondepressed comparison subjects.
|
|
| 7. |
- Pomara, Nunzio, et al.
(author)
-
State-dependent alterations in cerebrospinal fluid Aβ42 levels in cognitively intact elderly with late-life major depression.
- 2016
-
In: Neuroreport. - 1473-558X. ; 27:14, s. 1068-71
-
Journal article (peer-reviewed)abstract
- Depression has been linked to Alzheimer's disease as either an increased risk factor for its development or as a prodromal symptom. The neurobiological basis for such an association, however, remains poorly understood. Numerous studies have examined whether changes in amyloid beta (Aβ) metabolism, which are implicated in the pathogenesis of Alzheimer's disease, are also found in depression. In this paper, we investigated the relationship between depressive symptoms and cerebrospinal fluid (CSF) Aβ indices in otherwise healthy, cognitively normal elderly with late-life major depression (LLMD) and controls using a longitudinal approach, which is a novel contribution toward the literature. Significantly lower levels of CSF Aβ42 were observed in the LLMD group at baseline and were associated with more severe depressive symptoms. During longitudinal follow-up, the depressed group remained cognitively unchanged, but was significantly less depressed than at baseline. A greater improvement in depressive symptoms was associated with increases in CSF Aβ42 levels in both groups. Increases in CSF Aβ42 and Aβ40 were also associated with increased CSF total-tau levels. Our results suggest that LLMD may be associated with state-dependent effects of CSF Aβ42 levels. Future studies should determine whether the association reflects state-dependent changes in neuronal activity and/or brain amyloid burden in depression.
|
|
| 8. |
- Pomara, Nunzio, et al.
(author)
-
TOMM40 poly-T variants and cerebrospinal fluid amyloid beta levels in the elderly.
- 2011
-
In: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 36:6, s. 1124-8
-
Journal article (peer-reviewed)abstract
- A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer's disease in APOE ε3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, in cognitively intact elderly subjects. APOE ε4 carriers showed significant reductions in Aβ 1-42 levels compared to non-ε4 carriers, but no differences were detected across TOMM40 variants. Neither Aβ 1-40 nor tau levels were affected by APOE or TOMM40.
|
|
