Risk factors for transitions from normal to mild cognitive impairment and dementia

Kryscio, Richard J.; Schmitt, Frederick A.; Salazar, Juan Carlos; Mendiondo, Marta S.; Markesbery, William R.

doi:10.1212/01.wnl.0000203264.71880.45

Cited by 150 publications

(124 citation statements)

References 40 publications

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“…Data from the Mayo Clinic cohort, which is a relatively young group, demonstrated that APOE ε4 genotype is the best predictor of conversion to dementia [101]. These findings were recently confirmed by a longitudinal cohort study in which the presence of at least one APOE ε4 allele affected the transition from cognitively normal aging into amnestic MCI or into dementia [64]. According to these data, APOE ε4 may represent a predictor of dementia only for aMCI but not for other MCI subtypes.…”

Section: Predictors Of Progression Of MCI To Dementiamentioning

confidence: 84%

Mild Cognitive Impairment: A Systematic Review

Mariani

Monastero

Mecocci

2007

JAD

213

182

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Abstract. MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI (aMCI) characterized by reduced memory, and non-amnestic MCI (naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous -including vascular dementia, frontotemporal dementia or dementia with Lewy bodies-but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia.

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Section: Predictors Of Progression Of MCI To Dementiamentioning

confidence: 84%

Mild Cognitive Impairment: A Systematic Review

Mariani

Monastero

Mecocci

2007

JAD

213

182

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“…Some population-based studies have found the incidence of Alzheimer's disease to be higher among women, 30,[39][40][41] while others have not, 42,44,46 Devenand et al, in a smaller and slightly differently defined cohort of elderly subjects with mild memory impairment found no association between female sex and the development of dementia. 15 We confirm this finding in our cohort.…”

Section: Discussionmentioning

confidence: 96%

“…[36][37][38] Female gender has been noted to be a risk factor for dementia in a number of studies, 30,[39][40][41] although this has not been found in others. [42][43][44][45][46] The onset of subjective memory complaints may be a risk factor for development of subsequent cognitive decline. [47][48][49][50] Other research teams have, in contrast, noted that subjective complaints alone do not predict decline in the absence of objective memory loss.…”

Section: Clinical Risk Factors For Development Of Dementia and Admentioning

confidence: 99%

Can Clinical Data Predict Progression to Dementia in Amnestic Mild Cognitive Impairment?

Fellows

Bergman²,

Wolfson³

et al. 2008

Can. j. neurol. sci.

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314As treatments to alleviate symptoms and to slow the progression of Alzheimer's disease (AD) emerge, an increasingly urgent dilemma for physicians is also developing: which of the many elderly individuals with memory complaints will develop Alzheimer's disease, and would therefore be candidates for preventive therapies? An important goal of current research must be to establish useful pre-clinical diagnostic and predictive guidelines, and this can only emerge from longitudinal follow-up of elderly individuals with mild memory loss. In this paper, we report the clinical characteristics of such a group, with the aim of ABSTRACT: Background: To determine whether clinical data obtained by history and physical examination can predict eventual progression to dementia in a cohort of elderly people with mild cognitive impairment. Methods: A prospective, longitudinal study of a cohort of elderly subjects with amnestic Mild Cognitive Impairment (MCI). Ninety subjects meeting the criteria for amnestic MCI were recruited and followed annually for an average of 3.3 years. Main outcome measure was the development of dementia determined by clinical assessment with confirmatory neuropsychological evaluation. Results: Fifty patients (56%) developed dementia on follow-up. They were older, had lower Mini-mental status exam (MMSE) scores and a shorter duration of symptoms at the time of first assessment. Multivariate logistic regression analysis identified age at symptom onset as the only clinical parameter which distinguished the group that deteriorated to dementia from the group that did not. The odds ratio for age was 1.1 (confidence interval 1.04 -1.18). Conclusions: Patients presenting with amnestic MCI insufficient for the diagnosis of dementia are at high risk of developing dementia on follow-up. In our cohort, 56% were diagnosed with dementia over an average period of 5.9 years from symptom onset. The only clinical predictor for the eventual development of dementia was older age at symptom onset. Clinical features alone were insufficient to predict development of dementia.RÉSUMÉ: Les données cliniques peuvent-elles prédire la progression vers la démence dans l'atteinte cognitive légère avec syndrome amnésique? Contexte : Le but de cette étude était de déterminer si les données cliniques provenant de l'histoire médicale et de l'examen physique peuvent prédire la progression éventuelle vers la démence dans une cohorte de gens âgés ayant une atteinte cognitive légère. Méthodes : Il s'agit d'une étude longitudinale prospective d'une cohorte de sujets âgés ayant une atteinte cognitive légère (ACL). Quatre-vingt-dix sujets rencontrant les critères diagnostiques de l'ACL amnésique ont été recrutés et suivis annuellement pendant 3,3 ans en moyenne. Le critère d'évaluation principal était l'apparition d'une démence selon l'évaluation clinique confirmée par une évaluation neuropsychologique. Résultats : Cinquante patients (56%) ont développé une démence au cours du suivi. Ils étaient plus âgés, avaient des scores MMSE plus bas et u...

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“…Even in non-demented middle-aged and elderly human subjects, apoE4 is associated with greater cognitive decline, and the decline shows a gene doseresponse [31][32][33]. A significant association was found between apoE4 and transition from normal to mild cognitive impairment [34], which represents early-stage AD and with high positive predictive value for eventual conversion to AD [35].…”

Section: Discussionmentioning

confidence: 97%

Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice

Zhong

Scearce‐Levie

Ramaswamy

et al. 2008

Alzheimer's & Dementia

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BackgroundApolipoprotein E4 (apoE4), the major genetic risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases, has three structural and biophysical properties that distinguish it from the other isoforms—domain interaction, reduced stability, and lack of cysteine. Assessing their relative contributions to effects of apoE4‐associated pathogenesis in AD is important from a mechanistic and therapeutic perspective, that is not possible using human apoE transgene or knock‐in models.MethodsWe analyzed Arg‐61 apoE mice, a gene‐targeted model that selectively displays domain interaction.ResultsThe mice displayed age‐dependent loss of the synaptic protein synaptophysin in neocortex and hippocampus and had lower levels of the postsynaptic neuroligin‐1. Activation of dentate gyrus granule neurons increased Arc expression 3.5‐fold in wildtype mice but only 2.3‐fold in Arg‐61 mice. The losses of synaptic proteins caused a mild memory deficit in Arg‐61 mice in the water‐maze test. Since synaptic integrity requires efficient glutamate uptake, we measured astrocyte glutamate transporter 1 in the hippocampus. The level was reduced in Arg‐61 mice, suggesting that inefficient glutamate uptake by astrocytes causes chronic excitotoxicity. Consistent with the reduced secretion of Arg‐61 apoE by astrocytes in this model, cholesterol secretion was also reduced 34%. This reduction could also contribute to the synaptic deficits by limiting the availability of cholesterol for neuronal repair.ConclusionsDomain interaction in the absence of other structural characteristics of apoE4 is sufficient to cause synaptic pathology and functional synaptic deficits, potentially associated with astrocyte dysfunction and impaired maintenance of neurons. Therapeutic targeting of domain interaction might blunt effects of apoE4 in neurodegenerative disease.

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Risk factors for transitions from normal to mild cognitive impairment and dementia

Abstract: Aside from age, the usual risk factors associated with conversion from cognitively normal into dementia are likely risk factors for transitions into mild cognitive impairment.

Cited by 150 publications

References 40 publications

Mild Cognitive Impairment: A Systematic Review

Mild Cognitive Impairment: A Systematic Review

Can Clinical Data Predict Progression to Dementia in Amnestic Mild Cognitive Impairment?

Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice

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