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Cognitive decline

About: Cognitive decline is a research topic. Over the lifetime, 29308 publications have been published within this topic receiving 1174689 citations.


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Journal ArticleDOI
TL;DR: It is shown that the antiepileptic drug valproic acid (VPA) potently blocked seizure-induced neurogenesis, an effect that appeared to be mainly mediated by inhibiting histone deacetylases (HDAC) and normalizing HDAC-dependent gene expression within the epileptic dentate area.
Abstract: The conceptual understanding of hippocampal function has been challenged recently by the finding that new granule cells are born throughout life in the mammalian dentate gyrus (DG). The number of newborn neurons is dynamically regulated by a variety of factors. Kainic acid-induced seizures, a rodent model of human temporal lobe epilepsy, strongly induce the proliferation of DG neurogenic progenitor cells and are also associated with long-term cognitive impairment. We show here that the antiepileptic drug valproic acid (VPA) potently blocked seizure-induced neurogenesis, an effect that appeared to be mainly mediated by inhibiting histone deacetylases (HDAC) and normalizing HDAC-dependent gene expression within the epileptic dentate area. Strikingly, the inhibition of aberrant neurogenesis protected the animals from seizure-induced cognitive impairment in a hippocampus-dependent learning task. We propose that seizure-generated granule cells have the potential to interfere with hippocampal function and contribute to cognitive impairment caused by epileptic activity within the hippocampal circuitry. Furthermore, our data indicate that the effectiveness of VPA as an antiepileptic drug may be partially explained by the HDAC-dependent inhibition of aberrant neurogenesis induced by seizure activity within the adult hippocampus.

338 citations

Journal ArticleDOI
TL;DR: It is shown that transient depletion of Foxp3+ regulatory T cells (Tregs), or pharmacological inhibition of their activity, is followed by amyloid-β plaque clearance, mitigation of the neuroinflammatory response and reversal of cognitive decline in AD.
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder in which chronic neuroinflammation contributes to disease escalation. Nevertheless, while immunosuppressive drugs have repeatedly failed in treating this disease, recruitment of myeloid cells to the CNS was shown to play a reparative role in animal models. Here we show, using the 5XFAD AD mouse model, that transient depletion of Foxp3(+) regulatory T cells (Tregs), or pharmacological inhibition of their activity, is followed by amyloid-β plaque clearance, mitigation of the neuroinflammatory response and reversal of cognitive decline. We further show that transient Treg depletion affects the brain's choroid plexus, a selective gateway for immune cell trafficking to the CNS, and is associated with subsequent recruitment of immunoregulatory cells, including monocyte-derived macrophages and Tregs, to cerebral sites of plaque pathology. Our findings suggest targeting Treg-mediated systemic immunosuppression for treating AD.

338 citations

Journal ArticleDOI
TL;DR: Assessment of apathy in Alzheimer's disease requires clinicians to distinguish loss of motivation from loss of ability due to cognitive decline, and current research has shown apathy to be a discrete syndrome.
Abstract: Apathy, or loss of motivation, is arguably the most common change in behavior in Alzheimer's disease (AD) but is underrecognized. Apathy represents a form of executive cognitive dysfunction. Patients with apathy suffer from decreased daily function and specific cognitive deficits and rely on families to provide more care, which results in increased stress for families. Apathy is one of the primary syndromes associated with frontal and subcortical pathology, and apathy in AD appears to have multiple neuroanatomical correlates that implicate components of frontal subcortical networks. Despite the profound effects of this common syndrome, only a few instruments have been designed to specifically assess apathy, and these instruments have not been directly compared. Assessment of apathy in AD requires clinicians to distinguish loss of motivation from loss of ability due to cognitive decline. Although apathy may be misdiagnosed as depression because of an overlap in symptoms, current research has shown apathy to be a discrete syndrome. Distinguishing apathy from depression has important treatment implications, because these disorders respond to different interventions. Further research is required to clarify the specific neuroanatomical and neuropsychological correlates of apathy and to determine how correct diagnosis and treatment of apathy may improve patient functioning and ease caregiver burden.

338 citations

Journal ArticleDOI
TL;DR: High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age, and the association remained significant with further control of cardiovascular-related conditions and risk factors.
Abstract: Objective: To examine the association between rates of cognitive change and dietary consumption of fruits and vegetables among older persons Methods: The authors conducted a prospective cohort study of 3,718 participants, aged 65 years and older of the Chicago Health and Aging Project Participants completed a food frequency questionnaire and were administered at least two of three cognitive assessments at baseline, 3-year, and 6-year follow-ups Cognitive function was measured using the average z-score of four tests: the East Boston Tests of immediate memory and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test Results: The mean cognitive score at baseline for the analyzed cohort was 018 (range: –35 to 16), and the overall mean change in score per year was a decline of 004 standardized units In mixed effects models adjusted for age, sex, race, and education, compared with the rate of cognitive decline among persons in the lowest quintile of vegetable intake (median of 09 servings/day), the rate for persons in the fourth quintile (median, 28 servings/day) was slower by 0019 standardized units per year ( p = 001), a 40% decrease, and by 0018 standardized units per year ( p = 002) for the fifth quintile (median, 41 servings/day), or a 38% decrease in rates The association remained significant ( p for linear trend = 002) with further control of cardiovascular-related conditions and risk factors Fruit consumption was not associated with cognitive change Conclusion: High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age

337 citations

Journal ArticleDOI
TL;DR: By generating biomarker profiles that encompass peripheral metabolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and cognitive decline can be created.

336 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023914
20221,895
20213,389
20202,982
20192,551
20182,022