There is a limited number of studies evaluating the accuracy of the Mini-Cog for the diagnosis of dementia in primary care settings. Given the small number of studies, the wide range in estimates of the accuracy of the Mini-Cog, and methodological limitations identified in most of the studies, at the present time there is insufficient evidence to recommend that the Mini-Cog be used as a screening test for dementia in primary care. Further studies are required to determine the accuracy of Mini-Cog in primary care and whether this tool has sufficient diagnostic test accuracy to be useful as a screening test in this setting.

Background Objectives Search methods Selection criteria Data collection and analysis Main results Authors' conclusions Plain language summary DTA13 Mini-Cog for the diagnosis of Alzheimer's disease dementia and other dementias within a secondary care setting Approximately 50% to 80% of all individuals with dementia are ultimately classified as AD (Blennow 2006; Brunnstrom 2009; Canadian Study of Health and Aging 1994). While patients with dementias share common characteristics, subtle differences can help to provide a diagnosis in the absence of neuropathological examination. Vascular dementias may occur more abruptly or present with a step-wise decline in cognitive functions over time, and account for approximately 15% to 20% of dementias (Canadian Study of Health and Aging 1994; Feldman 2003; Lobo 2000). Dementia with a mixed vascular and Alzheimer's disease pathology is present in 10% to 30% of cases (Brunnstrom 2009; Crystal 2000; Feldman 2003). A smaller proportion of dementias are associated with dementia with Lewy bodies (Brunnstrom 2009) or Parkinson's disease dementia (Aarsland 2005). Patients experiencing frontotemporal dementia account for a smaller proportion of dementias (4% to 8%) and often present with problems in executive function and changes in behaviour, while memory is relatively preserved early in the disease course (Brunnstrom 2009; Greicius 2002). Index test(s) The Mini-Cog is a brief cognitive test consisting of two components, a delayed three word recall and the clock drawing test (Borson 2000). The Mini-Cog was initially developed in a community setting to provide a relatively brief cognitive screening test that was free of educational and cultural biases. Different scoring algorithms were tested to determine which combination had the optimal balance of sensitivity and specificity (McCarten 2011; Scanlan 2001). The Mini-Cog takes approximately three to five minutes to complete in routine practice (Borson 2000; Holsinger 2007; Scanlan 2001). The Mini-Cog has been reported to have little potential for bias with education or language (Borson 2000; Borson 2005). Clinical Pathway Dementia typically begins with subtle cognitive changes and progresses gradually over the course of several years. There is a presumed period when people are asymptomatic although the disease pathology may be progressing. Individuals or their relatives may first notice subtle impairments of short-term memory or other areas of cognitive functioning. Gradually, the severity of cognitive deficits become apparent resulting in difficulty completing complex activities of daily living such as management of finances and medications, or operating motor vehicles (Njegovan 2001). The attribution of cognitive symptoms to normal aging may cause delays in the diagnosis and treatment of AD or other types of dementia. Therefore, there is a need for accurate brief cognitive screening tests to help distinguish between the cognitive changes associated with normal aging and changes that might indicate a dementia. In a secondary care set...

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Breast tumors that overexpress human epidermal growth factor receptor 2 (HER2+) grow and spread faster than HER2-negative tumors, resulting in poor patient prognosis. Peroxisome proliferator-activated receptor (PPAR)γ is a nuclear transcription factor that controls the expression of genes essential for normal metabolism of fats and sugars in the body. Our laboratory previously showed that PPARγ expression suppresses environmental carcinogen DMBA-mediated breast tumor progression in vivo, and PPARγ-activating drugs further enhance this effect. However, the role of PPARγ and PPARγ agonists on HER2+ breast tumorigenesis and patient survival is unclear. We hypothesized that PPARγ loss enhances HER2+ breast tumor progression. To test this, this study generated a novel mouse model referred to as NIC:PPARγ-KO, which has targeted PPARγ deletion in the same HER2+ transformed mammary epithelial cells that drive breast tumorigenesis. Compared to NIC:PPARγ-WT mice, NIC:PPARγ-KO mice have increased mammary tumor incidences and lung metastases. Protein analysis of NIC:PPARγ-KO tumors shows PPARγ loss is inversely correlated with increased HER2 phosphorylation at tyrosine 877 (pY877HER2) in primary and metastatic tumorigenic tissue. Immunofluorescence also showed HER2 H-scores were significantly highest among tumors from NIC:PPARγ-KO mice, but also correlated with targeted PPARγ loss in DMBA-induced primary and metastatic mammary tumors among PPARγ-WT and PPARγ-KO mice (p<0.05). To further investigate the role of PPARγ in the metastatic process, we established cell lines from the freshly isolated lung metastatic tumors harvested from the NIC:PPARγ-KO model (NIC:PPARγ-KO-lmet). In vitro analysis of several human HER2+ breast cancer cells lines and our NIC:PPARγ-KO-lmet cells shows migration, invasion and tumorsphere-forming potential were significantly increased after epidermal growth factor (EGF, 20ng/mL) treatment and, more interestingly, that co-treatment with a PPARγ-activating drug (rosiglitazone, 10μM) significantly abrogated these effects (p<0.05). Together, these data provide the first evidence that PPARγ may be a useful prognostic/predictive biomarker for HER2+ breast tumors, and suggest that the novel inclusion of PPARγ-activating drugs may benefit a subset of HER2+ breast cancer patients. Citation Format: Elizabeth D. Lightbody, Kathleen MJ O'Connell, Hailey T. Newton, Rachel R. Rubino, Anthony J. Apostoli, Kevin Ren, Sandip K. SenGupta, Christopher J. Nicol. PPARγ loss increases the metastatic potential of HER2+ breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 110.

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