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Translational Assays for Assessment of Cognition in Rodent Models of Alzheimer’s Disease and Dementia

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Abstract

Cognitive dysfunction appears as a core feature of dementia, which includes its most prevalent form, Alzheimer’s disease (AD), as well as vascular dementia, frontotemporal dementia, and other brain disorders. AD alone affects more than 45 million people worldwide, with growing prevalence in aging populations. There is no cure, and therapeutic options remain limited. Gene-edited and transgenic animal models, expressing disease-specific gene mutations, illuminate pathogenic mechanisms leading to cognitive decline in AD and other forms of dementia. To date, cognitive tests in AD mouse models have not been directly relevant to the clinical presentation of AD, providing challenges for translation of findings to the clinic. Touchscreen testing in mice has enabled the assessment of specific cognitive domains in mice that are directly relevant to impairments described in human AD patients. In this review, we provide context for how cognitive decline is measured in the clinic, describe traditional methods for assessing cognition in mice, and outline novel approaches, including the use of the touchscreen platform for cognitive testing. We highlight the limitations of traditional memory-testing paradigms in mice, particularly their capacity for direct translation into cognitive testing of patients. While it is not possible to expect direct translation in testing methodologies, we can aim to develop tests that engage similar neural substrates in both humans and mice. Ultimately, that would enable us to better predict efficacy across species and therefore improve the chances that a treatment that works in mice will also work in the clinic.

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References

  • Aggleton JP, Keith AB, Rawlins JN, Hunt PR, Sahgal A (1992) Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats. Behav Brain Res 52:61–71

    Article  CAS  PubMed  Google Scholar 

  • Alexander G, Hanna A, Serna V, Younkin L, Younkin S, Janus C (2011) Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer’s disease. Behav Brain Res 216:77–83. doi:10.1016/j.bbr.2010.07.016

    Article  CAS  PubMed  Google Scholar 

  • Ashe KH, Zahs KR (2010) Probing the biology of Alzheimer’s disease in mice. Neuron 66:631–645. doi:10.1016/j.neuron.2010.04.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balducci C et al. (2010) Cognitive deficits associated with alteration of synaptic metaplasticity precede plaque deposition in AbetaPP23 transgenic mice. J Alzheimer Dis: JAD 21:1367–1381

    CAS  Google Scholar 

  • Bardgett ME, Davis NN, Schultheis PJ, Griffith MS (2011) Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease Neurobiology of learning and memory 95:64–72. doi:10.1016/j.nlm.2010.10.008

  • Bartko SJ, Vendrell I, Saksida LM, Bussey TJ (2011) A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil. Psychopharmacology 214:537–548. doi:10.1007/s00213-010-2050-1

    Article  CAS  PubMed  Google Scholar 

  • Baruch K et al. (2015) Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun 6:7967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baudic S, Barba GD, Thibaudet MC, Smagghe A, Remy P, Traykov L (2006) Executive function deficits in early Alzheimer’s disease and their relations with episodic memory. Arch Clin Neuropsychol: Off J Natl Acad Neuropsychol 21:15–21. doi:10.1016/j.acn.2005.07.002

    Article  Google Scholar 

  • Beck LH, Bransome ED Jr, Mirsky AF, Rosvold HE, Sarason I (1956) A continuous performance test of brain damage. J Consult Psychol 20:343–350

    Article  CAS  PubMed  Google Scholar 

  • Benton AI (1992) Benton visual retention test, 5th edn. The Psychological Corportation, San Antonion

    Google Scholar 

  • Bettens K, Sleegers K, Van Broeckhoven C (2013) Genetic insights in Alzheimer’s disease. Lancet Neurol 12:92–104. doi:10.1016/S1474-4422(12)70259-4

    Article  CAS  PubMed  Google Scholar 

  • Bissonette GB, Powell EM (2012) Reversal learning and attentional set-shifting in mice. Neuropharmacol 62:1168–1174. doi:10.1016/j.neuropharm.2011.03.011

    Article  CAS  Google Scholar 

  • Blackwell AD, Sahakian BJ, Vesey R, Semple JM, Robbins TW, Hodges JR (2004) Detecting dementia: novel neuropsychological markers of preclinical Alzheimer’s disease. Dement Geriatr Cogn Disord 17:42–48. doi:10.1159/000074081

    Article  PubMed  Google Scholar 

  • Blanchard J, Martel G, Brayda-Bruno L, Nogues X, Micheau J (2011) Detection of age-dependent working memory deterioration in APP751SL mice. Behav Brain Res 218:129–137. doi:10.1016/j.bbr.2010.11.040

    Article  PubMed  Google Scholar 

  • Bondi MW, Jak AJ, Delano-Wood L, Jacobson MW, Delis DC, Salmon DP (2008) Neuropsychological contributions to the early identification of Alzheimer’s disease. Neuropsychol Rev 18:73–90. doi:10.1007/s11065-008-9054-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Boustani M, Peterson B, Hanson L, Harris R, Lohr KN, Force USPST (2003) Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 138:927–937

    Article  PubMed  Google Scholar 

  • Brigman JL, Bussey TJ, Saksida LM, Rothblat LA (2005) Discrimination of multidimensional visual stimuli by mice: intra- and extradimensional shifts. Behav Neurosci 119:839–842. doi:10.1037/0735-7044.119.3.839

    Article  PubMed  Google Scholar 

  • Burgess A, Dubey S, Yeung S, Hough O, Eterman N, Aubert I, Hynynen K (2014) Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology 273:736–745

    Article  PubMed  PubMed Central  Google Scholar 

  • Burrows EL, Hannan AJ (2013) Towards environmental construct validity in animal models of CNS disorders: optimizing translation of preclinical studies. CNS Neurol Disord Drug Targets 12:587–592

    Article  CAS  PubMed  Google Scholar 

  • Burrows EL, Hannan AJ (2016) Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia. Biol Psychol 116:82–89. doi:10.1016/j.biopsycho.2015.11.015

    Article  PubMed  Google Scholar 

  • Bussey TJ, Dias R, Amin E, Muir JL, Aggleton JP (2001) Perirhinal cortex and place-object conditional learning in the rat. Behav Neurosci 115:776–785

    Article  CAS  PubMed  Google Scholar 

  • Bussey TJ et al. (2012) New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology 62:1191–1203. doi:10.1016/j.neuropharm.2011.04.011

    Article  CAS  PubMed  Google Scholar 

  • Cantarella G et al. (2015) Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer’s disease. Brain J Neurol 138:203–216

    Article  Google Scholar 

  • Cao D, Lu H, Lewis TL, Li L (2007) Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282:36275–36282

    Article  CAS  PubMed  Google Scholar 

  • Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ (2007) Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci Off J Soc Neurosci 27:13357–13365

    Article  CAS  Google Scholar 

  • Chapman PF et al. (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2:271–276. doi:10.1038/6374

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Logge W, Low JK, Garner B, Karl T (2013) Novel behavioural characteristics of the APP(Swe)/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. Behav Brain Res 245:120–127

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Low JK, Logge W, Garner B, Karl T (2014) Novel behavioural characteristics of female APPSwe/PS1DeltaE9 double transgenic mice. Behav Brain Res 260:111–118. doi:10.1016/j.bbr.2013.11.046

    Article  PubMed  Google Scholar 

  • Chishti MA et al. (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276:21562–21570. doi:10.1074/jbc.M100710200

    Article  CAS  PubMed  Google Scholar 

  • Chudasama Y (2011) Animal models of prefrontal-executive function. Behav Neurosci 125:327–343. doi:10.1037/a0023766

    Article  PubMed  Google Scholar 

  • Chudasama Y, Muir JL (1997) A behavioural analysis of the delayed non-matching to position task: the effects of scopolamine, lesions of the fornix and of the prelimbic region on mediating behaviours by rats. Psychopharmacology 134:73–82

    Article  CAS  PubMed  Google Scholar 

  • Clinton LK et al. (2007) Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 28:76–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collie A, Maruff P, Darby DG, McStephen M (2003) The effects of practice on the cognitive test performance of neurologically normal individuals assessed at brief test-retest intervals. J Int Neuropsychol Soc: JINS 9:419–428. doi:10.1017/S1355617703930074

    Article  PubMed  Google Scholar 

  • Corcoran KA, Lu Y, Turner RS, Maren S (2002) Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer’s disease. Learn Mem 9:243–252. doi:10.1101/lm.51002

    Article  PubMed  PubMed Central  Google Scholar 

  • Cullen B, O’Neill B, Evans JJ, Coen RF, Lawlor BA (2007) A review of screening tests for cognitive impairment. J Neurol Neurosurg Psychiatry 78:790–799. doi:10.1136/jnnp.2006.095414

    Article  PubMed  Google Scholar 

  • da Silva BM, Bast T, Morris RG (2014) Spatial memory: behavioral determinants of persistence in the watermaze delayed matching-to-place task. Learn Mem 21:28–36. doi:10.1101/lm.032169.113

    PubMed Central  Google Scholar 

  • Dai T, Davey A, Woodard JL, Miller LS, Gondo Y, Kim SH, Poon LW (2013) Sources of variation on the mini-mental state examination in a population-based sample of centenarians. J Am Geriatr Soc 61:1369–1376. doi:10.1111/jgs.12370

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis KE, Eacott MJ, Easton A, Gigg J (2013a) Episodic-like memory is sensitive to both Alzheimer’s-like pathological accumulation and normal ageing processes in mice. Behav Brain Res 254:73–82. doi:10.1016/j.bbr.2013.03.009

    Article  PubMed  Google Scholar 

  • Davis KE, Easton A, Eacott MJ, Gigg J (2013b) Episodic-like memory for what-where-which occasion is selectively impaired in the 3xTgAD mouse model of Alzheimer’s disease. J Alzheimer Dis: JAD 33:681–698. doi:10.3233/JAD-2012-121543

    CAS  PubMed  Google Scholar 

  • Deadwyler SA, Bunn T, Hampson RE (1996) Hippocampal ensemble activity during spatial delayed-nonmatch-to-sample performance in rats. J Neurosci Off J Soc Neurosci 16:354–372

    CAS  Google Scholar 

  • Dere E, Huston JP, De Souza Silva MA (2007) The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents. Neurosci Biobehav Rev 31:673–704. doi:10.1016/j.neubiorev.2007.01.005

    Article  CAS  PubMed  Google Scholar 

  • Dickson PE, Calton MA, Mittleman G (2014) Performance of C57BL/6J and DBA/2J mice on a touchscreen-based attentional set-shifting task. Behav Brain Res 261:158–170. doi:10.1016/j.bbr.2013.12.015

    Article  PubMed  Google Scholar 

  • Dong H, Csernansky CA, Martin MV, Bertchume A, Vallera D, Csernansky JG (2005) Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease. Psychopharmacology 181:145–152. doi:10.1007/s00213-005-2230-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eichenbaum H (2000) A cortical-hippocampal system for declarative memory. Nat Rev Neurosci 1:41–50. doi:10.1038/35036213

    Article  CAS  PubMed  Google Scholar 

  • Falleti MG, Maruff P, Collie A, Darby DG (2006) Practice effects associated with the repeated assessment of cognitive function using the CogState battery at 10-minute, one week and one month test-retest intervals. J Clin Exp Neuropsychol 28:1095–1112. doi:10.1080/13803390500205718

    Article  PubMed  Google Scholar 

  • Filali M (2012) Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer’s disease expressing mutated APP, PS and Mapt (3xTg-AD). Behav Brain Res 234 1 SRC - GoogleScholar:334–342

  • Filali M, Lalonde R (2009) Age-related cognitive decline and nesting behavior in an APPswe/PS1 bigenic model of Alzheimer’s disease. Brain Res 1292:93–99

    Article  CAS  PubMed  Google Scholar 

  • Filali M, Lalonde R, Rivest S (2011) Subchronic memantine administration on spatial learning, exploratory activity, and nest-building in an APP/PS1 mouse model of Alzheimer’s disease. Neuropharmacology 60:930–936

    Article  CAS  PubMed  Google Scholar 

  • Filali M, Lalonde R, Theriault P, Julien C, Calon F, Planel E (2012) Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer’s disease expressing mutated APP, PS1, and Mapt (3xTg-AD). Behav Brain Res 234:334–342. doi:10.1016/j.bbr.2012.07.004

    Article  CAS  PubMed  Google Scholar 

  • Foldi NS, Lobosco JJ, Schaefer LA (2002) The effect of attentional dysfunction in Alzheimer’s disease: theoretical and practical implications. Semin Speech Lang 23:139–150. doi:10.1055/s-2002-24990

    Article  PubMed  Google Scholar 

  • Fragkouli A, Tsilibary EC, Tzinia AK (2014) Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer’s 5xFAD mice. Neurobiol Dis 70:179–189

    Article  CAS  PubMed  Google Scholar 

  • Francis BM et al. (2012) Reduced tissue levels of noradrenaline are associated with behavioral phenotypes of the TgCRND8 mouse model of Alzheimer’s disease. Neuropsychopharm: Off Publ Am Coll Neuropsychopharmacol 37:1934–1944

    Article  CAS  Google Scholar 

  • Franco R, Cedazo-Minguez A (2014) Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans? Front Pharmacol 5:146. doi:10.3389/fphar.2014.00146

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fratiglioni L, Jorm AF, Grut M, Viitanen M, Holmen K, Ahlbom A, Winblad B (1993) Predicting dementia from the mini-mental state examination in an elderly population: the role of education. J Clin Epidemiol 46:281–287

    Article  CAS  PubMed  Google Scholar 

  • Freidl W, Schmidt R, Stronegger WJ, Irmler A, Reinhart B, Koch M (1996) Mini mental state examination: influence of sociodemographic, environmental and behavioral factors and vascular risk factors. J Clin Epidemiol 49:73–78

    Article  CAS  PubMed  Google Scholar 

  • Gaffan D, Parker A (1996) Interaction of perirhinal cortex with the fornix-fimbria: memory for objects and “object-in-place” memory. J Neurosci Off J Soc Neurosci 16:5864–5869

    CAS  Google Scholar 

  • Garner JP, Thogerson CM, Wurbel H, Murray JD, Mench JA (2006) Animal neuropsychology: validation of the intra-dimensional extra-dimensional set shifting task for mice. Behav Brain Res 173:53–61. doi:10.1016/j.bbr.2006.06.002

    Article  PubMed  Google Scholar 

  • Giannoni P (2013) Early administration of RS 67333, a specific receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer’s disease. Front Aging Neurosci 5 96:5-HT4

  • Gil-Bea FJ, Aisa B, Schliebs R, Ramirez MJ (2007) Increase of locomotor activity underlying the behavioral disinhibition in tg2576 mice. Behav Neurosci 121:340–344. doi:10.1037/0735-7044.121.2.340

    Article  PubMed  Google Scholar 

  • Gilbert PE, Kesner RP, DeCoteau WE (1998) Memory for spatial location: role of the hippocampus in mediating spatial pattern separation. J Neurosci Off J Soc Neurosci 18:804–810

    CAS  Google Scholar 

  • Giralt A, Saavedra A, Carreton O, Xifro X, Alberch J, Perez-Navarro E (2011) Increased PKA signaling disrupts recognition memory and spatial memory: role in Huntington’s disease. Hum Mol Genet 20:4232–4247. doi:10.1093/hmg/ddr351

    Article  CAS  PubMed  Google Scholar 

  • Girard SD et al. (2013) Evidence for early cognitive impairment related to frontal cortex in the 5XFAD mouse model of Alzheimer’s disease. J Alzheimer Dis: JAD 33:781–796

    CAS  PubMed  Google Scholar 

  • Girard SD et al. (2014) Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer’s disease. Hippocampus 24:762–772

    Article  CAS  PubMed  Google Scholar 

  • Görtz N, Lewejohann L, Tomm M, Ambrée O, Keyvani K, Paulus W, Sachser N (2008) Effects of environmental enrichment on exploration, anxiety, and memory in female TgCRND8 Alzheimer mice. Behav Brain Res 191:43–48

    Article  PubMed  CAS  Google Scholar 

  • Greco SJ et al. (2010) Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer’s disease. J Alzheimer Dis: JAD 19:1155–1167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grootendorst J et al. (2005) Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav Brain Res 159:1–14. doi:10.1016/j.bbr.2004.09.019

    Article  CAS  PubMed  Google Scholar 

  • Guérin D, Sacquet J, Mandairon N, Jourdan F, Didier A (2009) Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol Aging 30:272–283

    Article  PubMed  CAS  Google Scholar 

  • Guo HB et al. (2015) Donepezil improves learning and memory deficits in APP/PS1 mice by inhibition of microglial activation. Neuroscience 290:530–542

    Article  CAS  PubMed  Google Scholar 

  • Hampson RE, Deadwyler SA (1996) Ensemble codes involving hippocampal neurons are at risk during delayed performance tests. Proc Natl Acad Sci U S A 93:13487–13493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herremans AH, Hijzen TH, Welborn PF, Olivier B, Slangen JL (1996) Effects of infusion of cholinergic drugs into the prefrontal cortex area on delayed matching to position performance in the rat. Brain Res 711:102–111

    Article  CAS  PubMed  Google Scholar 

  • Holcomb L et al. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 4:97–100

    Article  CAS  PubMed  Google Scholar 

  • Holcomb LA, Gordon MN, Jantzen P, Hsiao K, Duff K, Morgan D (1999) Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet 29:177–185

    Article  CAS  PubMed  Google Scholar 

  • Hooijmans CR et al. (2009) DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis 33:482–498

    Article  CAS  PubMed  Google Scholar 

  • Hsiao K et al. (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102

    Article  CAS  PubMed  Google Scholar 

  • Hughes RN (1990) Phylogenetic comparisions. In Spontaneuos Alternation Behavior. Springer Verlag, New York

  • Hyde LA et al. (2005) Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice. Behav Brain Res 160:344–355

    Article  CAS  PubMed  Google Scholar 

  • Jankowsky JL et al. (2005) Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease. J Neurosci Off J Soc Neurosci 25:5217–5224

    Article  CAS  Google Scholar 

  • Jiao S-S et al. (2015) Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits. Proc Natl Acad Sci U S A 112:5225–5230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joels M, Baram TZ (2009) The neuro-symphony of stress. Nat Rev Neurosci 10:459–466. doi:10.1038/nrn2632

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jones RN, Gallo JJ (2002) Education and sex differences in the mini-mental state examination: effects of differential item functioning. J Gerontol Ser B Psychol Sci Soc Sci 57:P548–P558

    Article  Google Scholar 

  • Kapadia M, Xu J, Sakic B (2016) The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference. Neurosci Biobehav Rev 68:195–217. doi:10.1016/j.neubiorev.2016.05.016

    Article  PubMed  Google Scholar 

  • Kesner RP, Lee I, Gilbert P (2004) A behavioral assessment of hippocampal function based on a subregional analysis. Rev Neurosci 15:333–351

    Article  PubMed  Google Scholar 

  • Kim CH et al. (2015a) The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function. Psychopharmacology 232:3947–3966. doi:10.1007/s00213-015-4081-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim CH et al. (2015b) Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction. Psychopharmacology 232:3935–3945. doi:10.1007/s00213-015-4017-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim HY, Kim HV, Jo S, Lee CJ, Choi SY, Kim DJ, Kim Y (2015c) EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques. Nat Commun 6:8997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King DL, Arendash GW (2002) Behavioral characterization of the Tg2576 transgenic model of Alzheimer’s disease through 19 months. Physiol Behav 75:627–642

    Article  CAS  PubMed  Google Scholar 

  • King DL, Arendash GW, Crawford F, Sterk T, Menendez J, Mullan MJ (1999) Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer’s disease. Behav Brain Res 103:145–162

    Article  CAS  PubMed  Google Scholar 

  • Lalonde R, Qian S, Strazielle C (2003) Transgenic mice expressing the PS1-A246E mutation: effects on spatial learning, exploration, anxiety, and motor coordination. Behav Brain Res 138:71–79

    Article  CAS  PubMed  Google Scholar 

  • Lalonde R, Kim HD, Fukuchi K (2004) Exploratory activity, anxiety, and motor coordination in bigenic APPswe + PS1/DeltaE9 mice. Neurosci Lett 369:156–161

    Article  CAS  PubMed  Google Scholar 

  • Landes AM, Sperry SD, Strauss ME, Geldmacher DS (2001) Apathy in Alzheimer’s disease. J Am Geriatr Soc 49:1700–1707

    Article  CAS  PubMed  Google Scholar 

  • Lange KW, Sahakian BJ, Quinn NP, Marsden CD, Robbins TW (1995) Comparison of executive and visuospatial memory function in Huntington’s disease and dementia of Alzheimer type matched for degree of dementia. J Neurol Neurosurg Psychiatry 58:598–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leutgeb JK, Leutgeb S, Moser MB, Moser EI (2007) Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315:961–966. doi:10.1126/science.1135801

    Article  CAS  PubMed  Google Scholar 

  • Maliszewska-Cyna E, Xhima K, Aubert I (2016) A comparative study evaluating the impact of physical exercise on disease progression in a mouse model of Alzheimer’s disease. J Alzheimer Dis: JAD 53:243–257

    Article  CAS  Google Scholar 

  • Marchese M et al. (2014) Autoimmune manifestations in the 3xTg-AD model of Alzheimer’s disease. J Alzheimer Dis: JAD 39:191–210

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall SC, Mungas D, Weldon M, Reed B, Haan M (1997) Differential item functioning in the mini-mental state examination in English- and Spanish-speaking older adults. Psychol Aging 12:718–725

    Article  CAS  PubMed  Google Scholar 

  • Maruff P, Collie A, Darby DG, Weaver-Cargin D, McStephen M (2002) Subtle cognitive decline in mild cognitive impairment. (Technical document). CogStat Ltd, Australia

  • Masood T (2015) Determining attention deficits in mouse models of Alzheimer’s disease using touchscreen systems

  • McAllister KA, Saksida LM, Bussey TJ (2013) Dissociation between memory retention across a delay and pattern separation following medial prefrontal cortex lesions in the touchscreen TUNL task. Neurobiol Learn Mem 101:120–126. doi:10.1016/j.nlm.2013.01.010

    Article  PubMed  PubMed Central  Google Scholar 

  • McKhann GM et al. (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Dement: J Alzheimer Assoc 7:263–269. doi:10.1016/j.jalz.2011.03.005

    Article  Google Scholar 

  • Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683

    Article  CAS  PubMed  Google Scholar 

  • Musiek ES, Xiong DD, Holtzman DM (2015) Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease. Exp Mol Med 47:e148. doi:10.1038/emm.2014.121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musilli M, Nicolia V, Borrelli S, Scarpa S, Diana G (2013) Behavioral effects of Rho GTPase modulation in a model of Alzheimer’s disease. Behav Brain Res 237:223–229

    Article  CAS  PubMed  Google Scholar 

  • Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex; J Devoted Nerv Syst Behavs 12:313–324

    Article  CAS  Google Scholar 

  • Nelson RL et al. (2007) Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Exp Neurol 205:166–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nithianantharajah J et al. (2015) Bridging the translational divide: identical cognitive touchscreen testing in mice and humans carrying mutations in a disease-relevant homologous gene. Sci Rep 5:14613. doi:10.1038/srep14613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oddo S et al. (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39:409–421

    Article  CAS  PubMed  Google Scholar 

  • Ohno M (2009) Failures to reconsolidate memory in a mouse model of Alzheimer’s disease. Neurobiol Learn Mem 92:455–459

    Article  PubMed  PubMed Central  Google Scholar 

  • Oomen CA, Hvoslef-Eide M, Heath CJ, Mar AC, Horner AE, Bussey TJ, Saksida LM (2013) The touchscreen operant platform for testing working memory and pattern separation in rats and mice. Nat Protoc 8:2006–2021. doi:10.1038/nprot.2013.124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otalora BB et al. (2012) Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon. Chronobiol Int 29:822–834

    Article  CAS  Google Scholar 

  • Oules B et al. (2012) Ryanodine receptor blockade reduces amyloid-beta load and memory impairments in Tg2576 mouse model of Alzheimer disease. J Neurosci Off J Soc Neurosci 32:11820–11834. doi:10.1523/JNEUROSCI.0875-12.2012

    Article  CAS  Google Scholar 

  • Owen AM, Sahakian BJ, Semple J, Polkey CE, Robbins TW (1995) Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 33:1–24

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos P, Rosa-Neto P, Rochford J, Hamel E (2013) Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer’s disease with combined amyloid-beta and cerebrovascular pathology. PLoS One 8:e68612. doi:10.1371/journal.pone.0068612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parasuraman R (1979) Memory load and event rate control sensitivity decrements in sustained attention. Science 205:924–927

    Article  CAS  PubMed  Google Scholar 

  • Perry RJ, Watson P, Hodges JR (2000) The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment. Neuropsychologia 38:252–271

    Article  CAS  PubMed  Google Scholar 

  • Petrov D et al. (2015) High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents. Biochim Biophys Acta 1852:1687–1699

    Article  CAS  PubMed  Google Scholar 

  • Pietropaolo S, Feldon J, Yee BK (2008) Age-dependent phenotypic characteristics of a triple transgenic mouse model of Alzheimer disease. Behav Neurosci 122:733–747

    Article  PubMed  Google Scholar 

  • Pietropaolo S, Delage P, Lebreton F, Crusio WE, Cho YH (2012) Early development of social deficits in APP and APP-PS1 mice. Neurobiol Aging 33(1002):e1017–e1027. doi:10.1016/j.neurobiolaging.2011.09.012

    Google Scholar 

  • Pugh PL, Richardson JC, Bate ST, Upton N, Sunter D (2007) Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer’s disease. Behav Brain Res 178:18–28. doi:10.1016/j.bbr.2006.11.044

    Article  CAS  PubMed  Google Scholar 

  • Puolivali J, Wang J, Heikkinen T, Heikkila M, Tapiola T, van Groen T, Tanila H (2002) Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice. Neurobiol Dis 9:339–347. doi:10.1006/nbdi.2002.0481

    Article  PubMed  CAS  Google Scholar 

  • Puzzo D, Gulisano W, Palmeri A, Arancio O (2015) Rodent models for Alzheimer’s disease drug discovery. Expert Opin Drug Discovery 10:703–711. doi:10.1517/17460441.2015.1041913

    Article  CAS  Google Scholar 

  • Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344. doi:10.1056/NEJMra0909142

    Article  CAS  PubMed  Google Scholar 

  • Reiserer RS, Harrison FE, Syverud DC, McDonald MP (2007a) Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer’s disease. Genes Brain Behav 6:54–65. doi:10.1111/j.1601-183X.2006.00221.x

    Article  CAS  PubMed  Google Scholar 

  • Reiserer RS, Harrison FE, Syverud DC, McDonald MP (2007b) Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer’s disease. Genes Brain Behav 6:54–65

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163:362–380. doi:10.1007/s00213-002-1154-7

    Article  CAS  PubMed  Google Scholar 

  • Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM (2011) Impaired attention in the 3xTgAD mouse model of Alzheimer’s disease: rescue by donepezil (Aricept). J Neurosci Off J Soc Neurosci 31:3500–3507. doi:10.1523/JNEUROSCI.5242-10.2011

    Article  CAS  Google Scholar 

  • Romberg C, Bussey TJ, Saksida LM (2013a) Paying more attention to attention: towards more comprehensive cognitive translation using mouse models of Alzheimer’s disease. Brain Res Bull 92:49–55. doi:10.1016/j.brainresbull.2012.02.007

    Article  PubMed  Google Scholar 

  • Romberg C, Horner AE, Bussey TJ, Saksida LM (2013b) A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer’s disease. Neurobiol Aging 34:731–744

    Article  PubMed  PubMed Central  Google Scholar 

  • Romberg C, Horner AE, Bussey TJ, Saksida LM (2013c) A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer’s disease. Neurobiol Aging 34:731–744. doi:10.1016/j.neurobiolaging.2012.08.006

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ (2006) Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer’s disease. J Neurosci Off J Soc Neurosci 26:13384–13389

    Article  CAS  Google Scholar 

  • Ruggeri K, Maguire A, Andrews JL, Martin E, Menon S (2016) Are we there yet? Exploring the impact of translating cognitive tests for dementia using mobile technology in an aging population. Front Aging Neurosci 8:21. doi:10.3389/fnagi.2016.00021

    Article  PubMed  PubMed Central  Google Scholar 

  • Salmon DP, Bondi MW (2009) Neuropsychological assessment of dementia. Annu Rev Psychol 60:257–282. doi:10.1146/annurev.psych.57.102904.190024

    Article  PubMed  PubMed Central  Google Scholar 

  • Shirey JK et al. (2009) A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci Off J Soc Neurosci 29:14271–14286. doi:10.1523/JNEUROSCI.3930-09.2009

    Article  CAS  Google Scholar 

  • Shulman KI, Herrmann N, Brodaty H, Chiu H, Lawlor B, Ritchie K, Scanlan JM (2006) IPA survey of brief cognitive screening instruments. Int Psychogeriatr / IPA 18:281–294. doi:10.1017/S1041610205002693

    Article  Google Scholar 

  • Sierksma ASR, Rutten K, Sydlik S, Rostamian S, Steinbusch HWM, van den Hove DLA, Prickaerts J (2013) Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. Neuropharmacology 64:124–136

    Article  CAS  PubMed  Google Scholar 

  • Simons JS, Spiers HJ (2003) Prefrontal and medial temporal lobe interactions in long-term memory. Nat Rev Neurosci 4:637–648. doi:10.1038/nrn1178

    Article  CAS  PubMed  Google Scholar 

  • Sloan HL, Dobrossy M, Dunnett SB (2006) Hippocampal lesions impair performance on a conditional delayed matching and non-matching to position task in the rat. Behav Brain Res 171:240–250. doi:10.1016/j.bbr.2006.03.042

    Article  PubMed  Google Scholar 

  • Song H et al. (2015) Abeta-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease. Mol Neurodegener 10:13. doi:10.1186/s13024-015-0007-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stewart S, Cacucci F, Lever C (2011) Which memory task for my mouse? A systematic review of spatial memory performance in the Tg2576 Alzheimer’s mouse model. J Alzheimer Dis: JAD 26:105–126. doi:10.3233/JAD-2011-101827

    PubMed  Google Scholar 

  • Stover KR, Brown RE (2012) Age-related changes in visual acuity, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. Behav Brain Res 231:75–85

    Article  PubMed  Google Scholar 

  • Stover KR, Campbell MA, Van Winssen CM, Brown RE (2015) Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer’s disease. Behav Brain Res 289:29–38

    Article  CAS  PubMed  Google Scholar 

  • Taglialatela G, Hogan D, Zhang WR, Dineley KT (2009) Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition. Behav Brain Res 200:95–99. doi:10.1016/j.bbr.2008.12.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talpos JC, Winters BD, Dias R, Saksida LM, Bussey TJ (2009) A novel touchscreen-automated paired-associate learning (PAL) task sensitive to pharmacological manipulation of the hippocampus: a translational rodent model of cognitive impairments in neurodegenerative disease. Psychopharmacology 205:157–168. doi:10.1007/s00213-009-1526-3

    Article  CAS  PubMed  Google Scholar 

  • Talpos JC, McTighe SM, Dias R, Saksida LM, Bussey TJ (2010) Trial-unique, delayed nonmatching-to-location (TUNL): a novel, highly hippocampus-dependent automated touchscreen test of location memory and pattern separation. Neurobiol Learn Mem 94:341–352. doi:10.1016/j.nlm.2010.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tangalos EG et al. (1996) The mini-mental state examination in general medical practice: clinical utility and acceptance. Mayo Clin Proc 71:829–837. doi:10.1016/S0025-6196(11)63745-2

    Article  CAS  PubMed  Google Scholar 

  • Tapia-Rojas C, Aranguiz F, Varela-Nallar L, Inestrosa NC, Decreases L (2015) Voluntary running attenuates memory changes and induces neurogenesis in a mouse model of Alzheimer’s disease brain pathol nana doi101111bpa12255 doi:10.1111/bpa.12255 SRC - GoogleScholar

  • Tohda C, Urano T, Umezaki M, Nemere I, Kuboyama T (2012) Diosgenin is an exogenous activator of 25D3-MARRS/Pdia3/ERp57 and improves Alzheimer’s disease pathologies in 5XFAD mice Sci Rep 2 1 SRC - GoogleScholar

  • Vloeberghs E, Van Dam D, Coen K, Staufenbiel M, De Deyn PP (2006) Aggressive male APP23 mice modeling behavioral alterations in dementia. Behav Neurosci 120:1380–1383. doi:10.1037/0735-7044.120.6.1380

    Article  PubMed  Google Scholar 

  • Walker JM et al. (2011) Spatial learning and memory impairment and increased locomotion in a transgenic amyloid precursor protein mouse model of Alzheimer’s disease. Behav Brain Res 222:169–175. doi:10.1016/j.bbr.2011.03.049

    Article  CAS  PubMed  Google Scholar 

  • Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5:88. doi:10.3389/fgene.2014.00088

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wechsler D (1997) Wechsler memory scale. 3rd Edition Manual. The Psychological Corperation, San Antonio, TX

  • Weintraub S, Wicklund AH, Salmon DP (2012) The neuropsychological profile of Alzheimer disease. Cold Spring Harbor Perspect Med 2:a006171. doi:10.1101/cshperspect.a006171

    Article  Google Scholar 

  • Wild K, Howieson D, Webbe F, Seelye A, Kaye J (2008) Status of computerized cognitive testing in aging: a systematic review. Alzheime Dement: J Alzheimer Assoc 4:428–437. doi:10.1016/j.jalz.2008.07.003

    Article  Google Scholar 

  • Wilkinson RT (1963) Interaction of noise with knowledge of results and sleep deprivation. J Exp Psychol 66:332–337

    Article  CAS  PubMed  Google Scholar 

  • Wolf A, Bauer B, Abner EL, Ashkenazy-Frolinger T, Hartz AM (2016) A comprehensive behavioral test battery to assess learning and memory in 129S6/Tg2576 mice. PLoS One 11:e0147733. doi:10.1371/journal.pone.0147733

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang E et al. (2015) Phloroglucinol attenuates the cognitive deficits of the 5xFAD model of alzheimer’s disease. PloS One 10:e0135686 doi:10.1371/journal.pone.0135686

  • Yassine N et al. (2013) Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice. Neurobiol Aging 34:716–730. doi:10.1016/j.neurobiolaging.2012.06.016

    Article  CAS  PubMed  Google Scholar 

  • Young JW, Light GA, Marston HM, Sharp R, Geyer MA (2009) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS One 4:e4227. doi:10.1371/journal.pone.0004227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y et al. (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107:19014–19019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y et al. (2007) Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. J Neurosci Off J Soc Neurosci 27:13843–13853. doi:10.1523/JNEUROSCI.4486-07.2007

    Article  CAS  Google Scholar 

  • Zygouris S, Tsolaki M (2015) Computerized cognitive testing for older adults: a review. Am J Alzheimer Dis Dement 30:13–28. doi:10.1177/1533317514522852

    Article  Google Scholar 

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Acknowledgments

AJH is an NHMRC Senior Research Fellow and has been supported by an ARC FT3 Future Fellowship (FT100100835). ELB is supported by the NHMRC-ARC Dementia Research Development Fellowship (1111552). We would also like to acknowledge the operational infrastructure support from the State Government of Victoria.

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  1. Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, 3010, Australia

    A. Shepherd, S. Tyebji, A.J. Hannan & E.L. Burrows

  2. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, 3010, Australia

    A.J. Hannan

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  1. A. Shepherd
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  2. S. Tyebji
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Shepherd, A., Tyebji, S., Hannan, A. et al. Translational Assays for Assessment of Cognition in Rodent Models of Alzheimer’s Disease and Dementia. J Mol Neurosci 60, 371–382 (2016). https://doi.org/10.1007/s12031-016-0837-1

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