Depression and the Risk of Alzheimer Disease

Andersen, Kjeld; Lolk, Annette; Kragh‐Sörensen, P.; Petersen, Niels Erik; Green, Anders

doi:10.1097/01.ede.0000152116.32580.24

Cited by 102 publications

(79 citation statements)

References 32 publications

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“…Risk increased with increasing age a finding that is consistent with the known decline of genetic risk with increasing age [102]. Other chronic inflammatory diseases, for example, depression [103], atherosclerosis [104], and obesity [105] have a clearer epidemiological basis for being proposed to be risk factors in the development of AD. For all of these risk factors the individual attributable risk is likely to be small [81,103,106].…”

Section: Environmental Factorssupporting

confidence: 66%

Systemic and Central Immunity in Alzheimer's Disease: Therapeutic Implications

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Holmes

2011

CNS Neuroscience & Therapeutics

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SUMMARYClinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system.

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Section: Environmental Factorssupporting

confidence: 66%

Systemic and Central Immunity in Alzheimer's Disease: Therapeutic Implications

Butchart

Holmes

2011

CNS Neuroscience & Therapeutics

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“…In addition, PET imaging studies revealed that cognitive status in patients with AD is inversely correlated with microglial activation, but not Aβ load. 52,53 Finally, in accordance with the above mentioned genome-wide association studies, 7,8 chronic inflammatory diseases and conditions in humans, including atherosclerosis, obesity, diabetes, depression, and periodontitis, [54][55][56][57][58][59][60] all represent either risk factors for or correlate strongly with the risk of late-onset AD.…”

Section: Inflammation-a Key Playermentioning

confidence: 96%

Deciphering the mechanism underlying late-onset Alzheimer disease

2012

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Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-(A) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between A and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of A accumulation in late-onset AD. Abstract | Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence ...

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“…Generally speaking, depression in later life shares some characteristics with frailty which also leads to deficits that change the course of normal aging, such as cognitive impairment (Andersen et al 2005); disability (Bruce 2001), fractures (Whooley et al 1999), pain, isolation (Tavares 2004), mortality (Laursen et al 2007) and frailty. The relationship between frailty and depression among elderly is known but not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Frailty and depressive symptoms in older adults: data from the FIBRA study - UNICAMP

Nascimento

Batistoni

Néri

2016

Psicol. Refl. Crít.

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The relationship between the presence of depression, as measured by total score on the GDS-15 scale, and both pre-frailty and frailty status in community-dwelling elderly was determined. Two thousand four hundred and two elderly residents from seven Brazilian cities (M = 72.3 years, SD = 5.5; 66 % female) were evaluated according to the five criteria comprising the frailty phenotype. Participants answered a self-report inventory of diseases, of performance on advanced and instrumental activities of daily living, and the Geriatric Depression Scale (GDS-15). The number and types of depressive symptoms were found to be higher among frail and pre-frail elderly. Thus, besides variability in depression prevalence among the frailty profiles there were also characteristic depressive symptoms for each profile of the syndrome.

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Depression and the Risk of Alzheimer Disease

Abstract: Depression was associated with an increased risk of Alzheimer disease. The odds ratios were lower than generally reported from follow-up studies and are similar to cross-sectional studies.

Cited by 102 publications

References 32 publications

Systemic and Central Immunity in Alzheimer's Disease: Therapeutic Implications

Systemic and Central Immunity in Alzheimer's Disease: Therapeutic Implications

Deciphering the mechanism underlying late-onset Alzheimer disease

Frailty and depressive symptoms in older adults: data from the FIBRA study - UNICAMP

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