Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer’s Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria)

Pußwald, Gisela; Lehrner, Johann; Hagmann, Michael; Dal‐Bianco, Peter; Benke, Thomas; Loitfelder, Marisa; Marksteiner, Josef; Mosbacher, Jochen A.; Ransmayr, Gerhard; Sanin, Guenter; Schmidt, Reinhold

doi:10.3233/jad-150188

Cited by 21 publications

(10 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, greater decline in verbal memory in female patients has also been described in other neurodegenerative disorders including Alzheimer's disease (AD; Chapman et al 2011;Pusswald et al 2015). Different hypotheses for this finding have been postulated, including the post-menopausal decrease in oestrogen levels (Henderson et al 1996), as well as less cognitive reserve in females (Chapman et al 2011), but also other explanations such as a more frontal metabolic impairment in women with AD (Herholz et al 2002), differences regarding topography and severity or cerebral perfusion, smaller volumes of the hippocampus and other structures in women with AD (Kidron et al 1997;Callen et al 2001Callen et al , 2004Ballmaier et al 2004) and differential effects of the apolipoprotein E (APOE)4 allele (Fleisher et al 2005).…”

Section: Discussionmentioning

confidence: 93%

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data

et al. 2016

View full text Add to dashboard Cite

Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

show abstract

Section: Discussionmentioning

confidence: 93%

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Pusswald et al . assessed gender-specific differences in cognitive dysfunction between male and female patients with mild to moderate AD, and they observed that disruption of verbal learning in early-stage disease was more pronounced in women than in men [71]. These data are in-line with an earlier meta-analysis of neurocognitive data pooled from 15 independent studies of AD patients ( n = 828 men; 1238 women), which revealed that male patients significantly outperform female patients when tested for verbal and visuospatial ability as well as recall of episodic and semantic memory [72].…”

Section: Introductionmentioning

confidence: 99%

Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Adav

2016

Mol Brain

View full text Add to dashboard Cite

Dementia is a syndrome associated with a wide range of clinical features including progressive cognitive decline and patient inability to self-care. Due to rapidly increasing prevalence in aging society, dementia now confers a major economic, social, and healthcare burden throughout the world, and has therefore been identified as a public health priority by the World Health Organization. Previous studies have established dementia as a ‘proteinopathy’ caused by detrimental changes in brain protein structure and function that promote misfolding, aggregation, and deposition as insoluble amyloid plaques. Despite clear evidence that pathological cognitive decline is associated with degenerative protein modifications (DPMs) arising from spontaneous chemical modifications to amino acid side chains, the molecular mechanisms that promote brain DPMs formation remain poorly understood. However, the technical challenges associated with DPM analysis have recently become tractable due to powerful new proteomic techniques that facilitate detailed analysis of brain tissue damage over time. Recent studies have identified that neurodegenerative diseases are associated with the dysregulation of critical repair enzymes, as well as the misfolding, aggregation and accumulation of modified brain proteins. Future studies will further elucidate the mechanisms underlying dementia pathogenesis via the quantitative profiling of the human brain proteome and associated DPMs in distinct phases and subtypes of disease. This review summarizes recent developments in quantitative proteomic technologies, describes how these techniques have been applied to the study of dementia-linked changes in brain protein structure and function, and briefly outlines how these findings might be translated into novel clinical applications for dementia patients. In this review, only spontaneous protein modifications such as deamidation, oxidation, nitration glycation and carbamylation are reviewed and discussed.

show abstract

“…Epidemiological studies indicate that women bear a greater burden of AD, due to increased prevalence and, possibly, incidence of the disease rev in (Lin and Doraiswamy, 2014). Women with mild cognitive impairment (MCI) or AD have greater longitudinal rates of cognitive and functional progression than men (Li and Singh, 2014; Lin et al, 2015; Mielke et al, 2014; Pusswald et al, 2015) Studies that utilize imaging techniques revealed significant sex-related dimorphism in the development of atrophy as assessed by MRI in various gray matter regions in patients with AD or MCI (Hua et al, 2010; Skup et al, 2011). Importantly, the imaging studies indicate that atrophy develops at an earlier stage of cognitive deterioration in women than in men.…”

Section: Introductionmentioning

confidence: 99%

Sex-related dimorphism in dentate gyrus atrophy and behavioral phenotypes in an inducible tTa:APPsi transgenic model of Alzheimer's disease

Melnikova

Park

Becker

et al. 2016

Neurobiology of Disease

View full text Add to dashboard Cite

Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relevant to human disease is unclear. Here we show that in AD mouse models that overexpress amyloid precursor protein (APP) under control of the prion protein promoter (PrP), female transgenic mice have higher APP expression than males, complicating interpretations of the role of sex-related factors in such models. By contrast, in a tTa:APPsi model, in which APP expression is driven by the tetracycline transactivator (tTa) from the CaMKIIα promoter, there are no sex-related differences in expression or processing of APP. In addition, the levels of Aβ dimers and tetramers, as well as Aβ peptide accumulation, are similar between sexes. Behavioral testing demonstrated that both male and female tTa:APPsi mice develop age-dependent deficits in spatial recognition memory and conditional freezing to context. These cognitive deficits were accompanied by habituation-associated hyperlocomotion and startle hyper-reactivity. Significant sex-related dimorphisms were observed, due to females showing earlier onsets of the deficits in conditioned freezing and hyperlocomotion. In addition, tTa:APPsi males but not females demonstrated a lack of novelty-induced activation. Both males and females showed atrophy of the dentate gyrus (DG) of the dorsal hippocampus, associated with widening of the pyramidal layer of the CA1 area in both sexes. Ventral DG was preserved. Sex-related differences were limited to the DG, with females showing more advanced degeneration than males. Collectively, our data show that the tTa:APPsi model is characterized by a lack of sex-related differences in APP expression, making this model useful in deciphering the mechanisms of sex differences in AD pathogenesis. Sex-related dimorphisms observed in this model under conditions of equal APP expression between sexes suggest a higher sensitivity of females to the effects of APP and/or Aβ production.

show abstract

Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer’s Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria)

Cited by 21 publications

References 38 publications

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data

Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Sex-related dimorphism in dentate gyrus atrophy and behavioral phenotypes in an inducible tTa:APPsi transgenic model of Alzheimer's disease

Contact Info

Product

Resources

About