FThe development of this test was supported by a UK Medical Research Council Senior Research Fellowship to NB. TH has received support from the Department of Psychology, University of York.
The presented study was supported by an Alzheimer&#39;s Research UK grant awarded to DC. DC is funded by the Cambridge National Institute of Health Research Biomedical Research Centre. All authors would like to thank&#160;all the patients and control subjects for their kind participation, as well as their respective institutions.

1. Participant selection criteria
<ol>
	<li>Select individuals who are not color-blind and have normal or corrected-to-normal vision.</li>
</ol>
2.Test Preparation
<ol>
	<li>Seat the patient or control participant in a quiet room.</li>
	<li>Ensure the patient or control participant has glasses to correct their vision, if applicable.</li>
</ol>
3. Practice Test
<ol>
	<li>Instruct the participant as follows: 
	&#34;In this test you will see a picture of a mountain landscape which you should study carefully. That picture will be followed by four similar landscapes seen from different points of view and under different conditions of lighting or weather.&#34; 
	&#34;One of the four pictures shows exactly the same place as in the previous picture, although it will be shown from a slightly different viewpoint and conditions of lighting or weather. Your task is to identify which of the four pictures shows the same place as the one you have just seen.&#34; 
	&#34;Focus on the layout of the scene (the shape and arrangement of mountains and other geographical features). 
	&#34;Which picture shows the place in the previous picture?&#34;</li>
	<li>Instruct the participant to complete 3 practice items.
	<ol>
		<li>Provide verbal feedback on these items where necessary, drawing participants&#39; attention to relevant features of the stimuli.</li>
		<li>During the practice phase, instruct the participant to ask for clarification if they are unsure about any aspect of the task, and reinforce the original instructions as necessary, before proceeding to the test items.</li>
	</ol>
	</li>
</ol>
4. Main Test
<ol>
	<li>Inform the participant that they will be given the main test, including how many questions to expect and how much time they will have on each. For example: &#34;Now you&#39;re going to do the main test. There are 15 questions in total, and they are just like the practice ones you have just done. I&#39;ll give you a short time to study each picture, and then you have about 20 sec within which to choose your answer.&#34;</li>
	<li>Present the test items and record responses, allowing the participant a total of 30 sec for each item. Turn the pages of the booklet to control the timing of the stimulus presentation and responses.</li>
	<li>Start timing when the sample image is presented.</li>
	<li>Show the sample image for 8 sec, then turn to a blank page (1 sec), then turn to the page containing the response images (1 sec) and then show the response images for up to 20 sec, or until the participant indicates their selection.</li>
	<li>Ask the participant to indicate their response by pointing to the selected image. Stop timing when the participant and has made their selection.</li>
	<li>Record the participant&#39;s response and the time taken to make that response on the corresponding response sheet, giving no feedback on whether the response is correct or not.</li>
</ol>
5.Test Scoring
<ol>
	<li>After the testing session, score the total number of correct responses (a simple raw total).</li>
</ol>

<ol>
	<li>Petersen, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mild+cognitive+impairment+as+a+diagnostic+entity.">Mild cognitive impairment as a diagnostic entity.</a> J Intern Med. 256 (3), 183-194 (2004).</li><li>Dubois, B., Feldman, H. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revising+the+definition+of+Alzheimer's+disease:+a+new+lexicon.">Revising the definition of Alzheimer's disease: a new lexicon.</a> Lancet Neurol. 9 (11), 1118-1127 (2010).</li><li>Albert, M. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+diagnosis+of+mild+cognitive+impairment+due+to+Alzheimer's+disease:+recommendations+from+the+National+Institute+on+Aging-Alzheimer's+Association+workgroups+on+diagnostic+guidelines+for+Alzheimer's+disease.">The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.</a> Alzheimers Dement. 7 (3), 270-279 (2011).</li><li>Siemers, E. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+3+solanezumab+trials:+Secondary+outcomes+in+mild+Alzheimer's+disease+patients.">Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients.</a> Alzheimers Dement. 12 (2), 110-120 (2015).</li><li>. "What is mild cognitive impairment (MCI)?" Available from: <a target="_blank" href="https://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=120">https://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=120</a> (2016)</li><li>Westman, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensitivity+and+specificity+of+medial+temporal+lobe+visual+ratings+and+multivariate+regional+MRI+classification+in+Alzheimer's+disease.">Sensitivity and specificity of medial temporal lobe visual ratings and multivariate regional MRI classification in Alzheimer's disease.</a> PLoS ONE. 6 (7), e22506 (2011).</li><li>Folstein, M. F. M., Folstein, S. E. S., McHugh, P. R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term="Mini-mental+state."+A+practical+method+for+grading+the+cognitive+state+of+patients+for+the+clinician.">"Mini-mental state." A practical method for grading the cognitive state of patients for the clinician.</a> J Psychiat Res. 12 (3), 189-198 (1975).</li><li>Arevalo-Rodriguez, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mini-Mental+State+Examination+(MMSE)+for+the+detection+of+Alzheimer's+disease+and+other+dementias+in+people+with+mild+cognitive+impairment+(MCI).">Mini-Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI).</a> Cochrane DB Syst Rev. 3, CD010783 (2015).</li><li>Prestia, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+accuracy+of+markers+for+prodromal+Alzheimer's+disease+in+independent+clinical+series.">Diagnostic accuracy of markers for prodromal Alzheimer's disease in independent clinical series.</a> Alzheimers Dement. 9 (6), 677-686 (2013).</li><li>Hartley, T. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hippocampus+is+required+for+short-term+topographical+memory+in+humans.">The hippocampus is required for short-term topographical memory in humans.</a> Hippocampus. 17 (1), 34-48 (2007).</li><li>Braak, H., Braak, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropathological+stageing+of+Alzheimer-related+changes.">Neuropathological stageing of Alzheimer-related changes.</a> Acta Neuropathol. 82 (4), 239-259 (1991).</li><li>Braak, H., Del Trecidi, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroanatomy+and+pathology+of+sporadic+Alzheimer's+disease.">Neuroanatomy and pathology of sporadic Alzheimer's disease.</a> Adv Anat Embryol Cel. 215, 1-162 (2015).</li><li>Gomez-Isla, T., Price, J. L., McKeel, D. W., Morris, J. C., Growdon, J. H., Hyman, B. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Profound+Loss+of+Layer+II+Entorhinal+Cortex+Neurons+Occurs+in+Very+Mild+Alzheimer's+Disease.">Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer's Disease.</a> J Neurosci. 16 (14), 4491-4500 (1996).</li><li>O'Keefe, J., Dostrovsky, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hippocampus+as+a+spatial+map.+Preliminary+evidence+from+unit+activity+in+the+freely-moving+rat.">The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat.</a> Brain Res. 34 (1), 171-175 (1971).</li><li>O'Keefe, J., Nadel, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The hippocampus as a cognitive map. , (1978).</li><li>Ekstrom, A. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cellular+networks+underlying+human+spatial+navigation.">Cellular networks underlying human spatial navigation.</a> Nature. 425 (6954), 184-188 (2003).</li><li>Burgess, N., Maguire, E. L., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+human+hippocampus+and+spatial+and+episodic+memory.">The human hippocampus and spatial and episodic memory.</a> Neuron. 15 (34 Pt 4), 625-641 (2002).</li><li>Bird, C. M., Chan, D., Hartley, T., Pijnenburg, Y. A., Rossor, M. N., Burgess, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topographical+short-term+memory+differentiates+Alzheimer's+disease+from+frontotemporal+lobar+degeneration.">Topographical short-term memory differentiates Alzheimer's disease from frontotemporal lobar degeneration.</a> Hippocampus. 20 (10), 1154-1169 (2009).</li><li>Pengas, G. G., Patterson, K. K., Arnold, R. J. R., Bird, C. M. C., Burgess, N. N., Nestor, P. J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lost+and+found:+bespoke+memory+testing+for+Alzheimer's+disease+and+semantic+dementia.">Lost and found: bespoke memory testing for Alzheimer's disease and semantic dementia.</a> Journal of Alzheimers Dis : JAD. 21 (4), 1347-1365 (2010).</li><li>Moodley, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+differentiation+of+mild+cognitive+impairment+due+to+Alzheimer's+disease+using+a+hippocampus-dependent+test+of+spatial+memory.">Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus-dependent test of spatial memory.</a> Hippocampus. 25 (8), 939-951 (2015).</li><li>Hartley, T. T., Harlow, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+association+between+human+hippocampal+volume+and+topographical+memory+in+healthy+young+adults.">An association between human hippocampal volume and topographical memory in healthy young adults.</a> Front Hum Neurosci. 6, 338 (2012).</li><li>Hartley, T., Lever, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Know+your+limits:+the+role+of+boundaries+in+the+development+of+spatial+representation.">Know your limits: the role of boundaries in the development of spatial representation.</a> Neuron. 82 (1), 1-3 (2014).</li><li>Burgess, N., Jeffery, K. J., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The hippocampal and parietal foundations of spatial cognition. , (1999).</li><li>Mioshi, E. E., Dawson, K. K., Mitchell, J. J., Arnold, R. R., Hodges, J. R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Addenbrooke's+Cognitive+Examination+Revised+(ACE-R):+a+brief+cognitive+test+battery+for+dementia+screening.">The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening.</a> Int J Geriatr Psychiatry. 21 (11), 1078-1085 (2006).</li><li>Moroney, J. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Meta-analysis+of+the+Hachinski+Ischemic+Score+in+pathologically+verified+dementias.">Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias.</a> Neurology. 49 (4), 1096-1105 (1997).</li><li>McKhann, G. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=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.">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.</a> Alzheimers Dement. , 263-269 (2011).</li><li>Mulder, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amyloid-+(1-42),+Total+Tau,+and+Phosphorylated+Tau+as+Cerebrospinal+Fluid+Biomarkers+for+the+Diagnosis+of+Alzheimer+Disease.">Amyloid- (1-42), Total Tau, and Phosphorylated Tau as Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer Disease.</a> Clin Chem. 56 (2), 248-253 (2010).</li><li>Nelson, H. E., Willison, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> National Adult Reading Test (NART). , (1991).</li><li>Rey, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=L'examen+psychologique+dans+les+cas+d'enc&#233;phalopathie+traumatique.+(Les+problems.).">L'examen psychologique dans les cas d'enc&#233;phalopathie traumatique. (Les problems.).</a> Arch Psychologie. , (1941).</li><li>Reitan, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validity+of+the+trail+making+test+as+an+indicator+of+organic+brain+damage.">Validity of the trail making test as an indicator of organic brain damage.</a> Percept and Motor. 8, 271-276 (1958).</li><li>Benton, A., Hamsher, K., Sivan, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Multilingual Aphasia Examination. , (1994).</li><li>Blackburn, H. L. H., Benton, A. L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revised+administration+and+scoring+of+the+digit+span+test.">Revised administration and scoring of the digit span test.</a> J Consult Psychol. 21 (2), 139-143 (1957).</li><li>James, M., Warrington, E. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The visual object and space perception battery. , (1991).</li><li>Fischl, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=FreeSurfer.">FreeSurfer.</a> NeuroImage. 62 (2), 774-781 (2012).</li><li>Desikan, R. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+automated+labeling+system+for+subdividing+the+human+cerebral+cortex+on+MRI+scans+into+gyral+based+regions+of+interest.">An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.</a> NeuroImage. 31 (3), 13 (2006).</li><li>Maguire, E. A., Burgess, N., Donnett, J. G., Frackowiak, R. S. J., Frith, C. D., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Knowing+where+and+getting+there:+a+human+navigation+network.">Knowing where and getting there: a human navigation network.</a> Science. 280 (5365), 921-924 (1998).</li><li>Buckner, R. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular,+structural+and+functional+characterization+of+Alzheimer's+disease:+evidence+for+a+relationship+between+default+activity,+amyloid+and+memory.">Molecular, structural and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid and memory.</a> J Neurosci. 25, 7709-7717 (2005).</li><li>Patenaude, B. B., Smith, S. M. S., Kennedy, D. N. D., Jenkinson, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Bayesian+model+of+shape+and+appearance+for+subcortical+brain+segmentation.">A Bayesian model of shape and appearance for subcortical brain segmentation.</a> NeuroImage. 56 (3), 907-922 (2011).</li><li>Greicius, M. D. M., Srivastava, G. G., Reiss, A. L. A., Menon, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Default-mode+network+activity+distinguishes+Alzheimer's+disease+from+healthy+aging:+evidence+from+functional+MRI.">Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI.</a> Proc Natl Acad Sci U S A. 101 (13), 4637-4642 (2004).</li><li>Vincent, J. L. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coherent+spontaneous+activity+identifies+a+hippocampal-parietal+memory+network.">Coherent spontaneous activity identifies a hippocampal-parietal memory network.</a> J Neurophysiol. 96 (6), 3517-3531 (2006).</li><li>Rombouts, S. A. R. B. S., Barkhof, F. F., Goekoop, R. R., Stam, C. J. C., Scheltens, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+resting+state+networks+in+mild+cognitive+impairment+and+mild+Alzheimer's+disease:+an+fMRI+study.">Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study.</a> Hum Brain Mapp. 26 (4), 231-239 (2005).</li></ol>

The authors declare that they do have not competing financial interests.

The 4 Mountains Test (4MT) is a short test of allocentric spatial memory which is sensitive to predementia AD&#160;in patients exhibiting MCI. Following on from previous studies showing that this test can differentiate between AD-related and non-AD-related dementia18, 19, 4MT scores differed significantly between groups of MCI patients with and without CSF biomarker evidence of AD, who were otherwise matched in terms of demographics, symptom duration, premorbid IQ and performance on general neuropsychometric testing. Of particular note, there was no significant difference between the 2 MCI groups in terms of Rey Auditory Verbal Learning Test (RAVLT) performance. The RAVLT is a widely used test of episodic memory, considered to have high diagnostic sensitivity for early AD, cited as one of the cognitive tests suitable for use in diagnosing MCI due to AD3. The ability of 4MT testing to detect the presence of early AD is further illustrated by measures of test sensitivity and specificity. A 4MT score of 8/15 or below was associated with 100% diagnostic sensitivity and 78% specificity for the detection of early AD in MCI patients, as demonstrated by biomarker evidence of AD. The related area under the Receiver Operating Characteristic curve was 0.93.
4MT scores correlated with hippocampal volume (r = 0.42) and with the cortical thickness of the precuneus (r = 0.55), consistent with the viewpoint that allocentric spatial memory in humans is subserved by a functional network that encompasses the hippocampus and the precuneus. Task-free fMRI studies show that the hippocampus and precuneus represent highly interconnected hubs within a &#34;default mode network&#34; underpinning spatial and episodic memory39, 40 and the findings of this recent study are in keeping with the vulnerability of this network to early AD41.
Taken together, the results obtained from several studies involving patients with MCI and AD prove the principle that the 4MT is a sensitive test for predementia AD. The potential added value of this test is highlighted by observations in this recent work that neither hippocampal volume, considered to be a biomarker of AD, or testing of episodic memory with the RAVLT, were able to discriminate between MCI patients with and without evidence of underlying AD. Further larger scale studies involving the 4MT are currently in progress that will address the major limitation of this study that relates to its relatively small sample size. These include longitudinal studies that assess the ability of 4MT performance to predict conversion of MCI to dementia and longitudinal studies in asymptomatic elders to determine if impaired 4MT performance may herald subsequent AD-related cognitive decline. AD versus non-AD specificity studies will address the question of test-retest reliability in patients rather than controls, as described in this paper.
Critical steps in test administration 
The test is straightforward to administer but care must be taken to provide accurate instructions and practice. In particular, pilot work with the task suggests that the wording of instructions is important, as the allocentric (view-independent) nature of the recognition task can seem unfamiliar. Participants may have idiosyncratic interpretations of terms such as &#34;scene&#34;, &#34;image&#34;, &#34;landscape&#34; but they do understand the phrase &#34;same place&#34; to encompass alternative views. A critical step in the protocol is ensuring that this element of the instruction has been understood before progressing from practice to test items.
Results suggest that the test is selectively sensitive to hippocampal pathology but, in principle, performance can be also limited by patient cooperation, motivation and attention (as affected by depression or anxiety, for example), by their understanding of the instructions and potentially by damage to other brain regions involved in vision and allocentric spatial memory. It is important therefore, that test participants are motivated and attentive and that inclusio&#160;/exclusion criteria and accompanying measures are sufficient to exclude alternative explanations for poor performance.
Test modification 
The 4MT is now being used as an outcome measure for interventional studies of anti-AD drugs, applied to people prior to dementia onset. In view of the need for repeated testing, an alternate 15-item form of the test, matched for test difficulty with the 15-item test used in 3 studies, has already been generated, notwithstanding the good test-retest reliability of the current stimuli. Further difficulty-matched 15-item alternate-version tests are currently being developed in order to facilitate multiple repeat testing within future longitudinal studies and treatment trials.
Several modifications to the protocol described above can be adopted. In the published clinical studies, patients and controls were tested with a 15-item topographical memory test. For research purposes other versions of the task may be useful. Perceptual (sample image remains visible during matching) and non-spatial variants (in which participants match texture, lighting and weather conditions rather than spatial organization) of the task have been used for comparison with topographical memory10 which might enable detection of confounding motivational or perceptual issues. In nonclinical studies with exclusively healthy participants21 a more challenging 30-item topographical memory test may be used.
Limitations of the technique 
Successful application of the 4MT requires visual function that is sufficiently intact to perceive the test stimuli.
In conclusion, the 4MT has several operational advantages which would favor its use as a diagnostic test for pre-dementia AD in routine clinical practice. Specifically, its brevity, ease of administration and non-invasive nature allows it to be used in nonspecialist, as well as specialist, clinical settings. In view of these advantages, ongoing work is exploring the feasibility of applying this test to larger patient cohorts derived from community-based memory clinics and hospital clinics, with prolonged follow-up to determine the ability of the 4MT to predict conversion from MCI to dementia. The provision of the 4MT in electronic form will facilitate the planned widespread adoption of this test as a clinical diagnostic tool.

Alzheimer&#39;s Disease (AD) is the most common cause of dementia and it is now understood that predementia stages of AD exist&#160;in the form&#160;of a clinically silent &#34;presymptomatic&#34; stage. A symptomatic / &#34;prodromal&#34; stage, manifests itself as mild cognitive impairment (MCI), in which individuals exhibit cognitive decline (typically memory impairment) but retain functional independence and preserved activities of daily living1. This clinical reconsideration of AD is reflected in the current sets of diagnostic criteria for AD2,3.
Diagnosis of AD in its predementia stages is critically important, not just for provision of best clinical care but also in light of the anticipated arrival of disease-modifying treatments for AD, given that such treatments are likely to be most effective if applied at earlier stages of the disease. This is illustrated by the recent clinical trials of the anti-amyloid drug solanezumab; while initial results failed to show any treatment effect, reevaluation of data on the subgroup of trial patients with milder disease found a significant effect on the trial&#39;s cognitive endpoints4.
However, MCI due to AD is very difficult to distinguish clinically from other causes of MCI, which also include nonneurodegenerative disorders such as anxiety. There is a need therefore for a test that is not only sensitive to AD-related dementia but also noninvasive and suitable for widespread use in routine clinical diagnostic practice. The latter requirement is crucial in view of the high prevalence of MCI in the ageing population, with an estimated prevalence of 5 - 20% in the UK population aged over 65 years5, many of whom will attend nonspecialist, community-based, memory clinics.
Current tests do not meet this need. Tests used to detect AD-related&#160;dementia (such as MRI scanning to determine whole brain or hippocampal atrophy) have reduced sensitivity when applied to the pre-dementia stages of AD6. The Mini Mental State Examination (MMSE)7 is the most widely used cognitive test in memory clinics but is insensitive, nonspecific and has poor predictive ability8. Biomarker-based tests, such as amyloid-PET or CSF studies of amyloid/tau, are good predictors of conversion to dementia9 but are invasive and expensive, and their restricted availability to select specialist clinics precludes their usage in routine clinical practice.
The 4 Mountains Test (4MT)10 may meet this need. The 4MT is a short test of working allocentric spatial memory (that assesses the ability of the participant to recall the spatial configuration of a series of computer-generated landscapes from a shifted viewpoint), designed to reflect the role of the hippocampus in spatial cognition. The scientific rationale for the use of such a test is founded on two principles, both supported by extensive research. The first is that the hippocampus and the related medial temporal lobe (MTL) structures are affected from the earliest stages of AD. Evidence for this is obtained from neuropathological studies of AD, which have shown that neurodegeneration is observed initially within the MTL, with involvement first of the entorhinal cortex and subsequently, the hippocampus11, 12. Severe neuronal loss in these regions is present even at the earliest stages of clinically-evident AD13. The second principle is that the hippocampus is critically involved in spatial memory. This originates from the initial demonstration of place-related firing activity of hippocampal neurons in freely moving rats14, which led to the &#34;cognitive map&#34; theory of hippocampal function15. Subsequent work has indicated that the human hippocampus has a similar role, with place-related activity observed during presurgical recordings from the hippocampal neurons of patients with temporal lobe epilepsy16, and with activation of the hippocampus in functional imaging studies during tasks involving spatial memory17.
The 4MT task and stimuli are described in Hartley et al. (2007)10. The same stimuli have been used in all later studies published to date18-21.
Each item in the 4MT is composed of 5 images of computer-generated landscapes as shown in Figure 1. Participants view a sample image and are then required to choose a target image from 4 alternatives, which shows the same place from a different viewpoint. The remaining 3 images are foils depicting landscapes whose topography differs systematically from the target landscape.
<img alt="Figure 1" src="/files/ftp_upload/54454/54454fig1.jpg" /> 
Figure 1. The Four Mountains Test (4MT). (A) All 4MT stimuli are based on computer-generated heightfields containing 4&#160;mountains as illustrated by a contour map for one example (see text for further details). Images are rendered using a virtual camera placed at one of the indicated 7 locations. (B) Participants see a sample image which they study before seeing four different images (one target showing the same place from a different view point, and 3 foils showing different places). Their task is to identify the target. (C) Example of a sample image. (D) Corresponding target and foil images (the target is seen top-left). Note that all images are shown at the same scale in the test, and that viewpoint and other nonspatial features are systematically varied between sample and test images. <a href="http://cloudflare.jove.com/files/ftp_upload/54454/54454fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Each landscape is made up of similar topographical features: the ground plane with small scale undulations, a semicircular mountain range (defining the horizon in each image), and 4 prominent mountains of varying shapes and sizes. An example is shown as a contour map in Figure 1A. Stimuli are selected from a large number of landscapes, created such that each has an unambiguously distinct global topography within which individual local features are shared between items and between target and foil landscapes. Landscapes used to generate foil images are created by varying the size shape and location of mountains in the sample/target landscape. This provides a set of foils sharing (to a similar degree across items) local topographical features, such that nonspatial strategies based on memory for local features would be ineffective. Sample and target images are rendered using the same topography but different camera locations. The aim of the viewpoint change is to encourage allocentric spatial strategies (exploiting spatial representations which are known to exist within the hippocampal formation, see Hartley et al., 2014 for a recent review22) and to discourage strategies based on egocentric or visual representations (which are known to exist outside the hippocampal formation, see Burgess, Jeffery &#38; O&#39;Keefe, 199923). The latter type of information is disrupted by the unpredictable shift of viewpoint, especially since several topographical features are common to both target and foil landscapes. To further discourage visual pattern matching strategies, the lighting, landscape colors and textures and weather conditions are varied between the sample and the test images. Each item thus comprises a sample image with one set of nonspatial features, a target image depicting the same landscape from a different viewpoint and different nonspatial features and 3 foil images with distinct topography but sharing nonspatial features with the target.
Following the demonstration that 4MT spatial memory performance (Place Memory; PM) was selectively impaired in patients with focal hippocampal damage, while spatial perception (Place Perception; PP), nonspatial memory and nonspatial perception were relatively spared10, this test was applied to patients with dementia. Results from separate research groups showed that the 4MT could differentiate patients with AD-related&#160;dementia, not only from age-matched control subjects but also from patients with other dementia-causing disorders18, 19.
More recently, the 4MT has been shown to discriminate MCI patients with and without biomarker evidence of underlying AD, illustrating its potential utility as a clinical test for predementia AD20. As part of the same study, the 4MT was successfully applied to an MCI patient cohort recruited from Italian memory clinics, demonstrating the utility of this test, the design of which is language-independent, in different clinical and cultural settings.
This paper describes the 4MT methodology and summarizes the results of the study on MCI patients, which are published in full in the paper by Moodley et al. (2015)20. In this study, performance on the 4MT was compared with structural measurements of key brain regions involved in spatial processing, namely the hippocampus, precuneus and posterior cingulate gyrus.

<table><tbody><tr><td>Four Mountains Test booklet</td><td></td><td></td><td>Available via Professor Neil Burgess and Dr. Tom Hartley. Test booklet can be assembled using an A4 file or similar.</td></tr><tr><td>Four Mountains Test response sheet</td><td></td><td></td><td>Available via Professor Neil Burgess and Dr. Tom Hartley. Response sheet is used to record participant&#039;s response and response time and to then generate raw totals.</td></tr></tbody></table>

the 4 mountains test: a short test of spatial memory with high sensitivity for the diagnosis of pre-dementia alzheimer's disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

Watch this Scientific Journal Video about The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease at JoVE.com

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

the-4-mountains-test-short-test-spatial-memory-with-high-sensitivity

Research

JoVE Journal

Behavior

32.2K Views.  University of Cambridge. This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD. 

Video: The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening ...

Neuroscience

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment

Mild cognitive impairment (MCI) is the first sign of dementia among elderly populations and its early detection is crucial in our aging societies. Common MCI tests are time-consuming such that indiscriminate massive screening would not be cost-effective. Here, we describe a protocol that uses machine learning techniques to rapidly select candidates for further screening via a question-based MCI test. This minimizes the number of resources required for screening because only patients who are potentially MCI positive are tested further.
This methodology was applied in an initial MCI research study that formed the starting point for the design of a selective screening decision tree. The initial study collected many demographic and lifestyle variables as well as details about patient medications. The Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE) were used to detect possible cases of MCI. Finally, we used this method to design an efficient process for classifying individuals at risk of MCI. This work also provides insights into lifestyle-related factors associated with MCI that could be leveraged in the prevention and early detection of MCI among elderly populations.

This methodology produces decision trees that target population groups more prone to suffering from mild cognitive impairment and are useful for cost-effective selective screening of the disease.

Mild cognitive impairment (MCI) is the first sign of dementia among elderly populations and its early detection is crucial in our aging societies. Common ...

Highlighting and Reducing the Impact of Negative Aging Stereotypes During Older Adults' Cognitive Testing

As life expectancy increases, aging has become a major health challenge, resulting in a huge effort to better discriminate between normal and pathological cognitive decline. It is thus essential that cognitive tests and their administration are as fair as possible. However, an important source of bias during cognitive testing comes from negative aging stereotypes that can impair the memory performance of older adults and inflate age differences on cognitive tasks. The fear of confirming negative aging stereotypes creates an extra pressure among older adults which interferes with their intellectual functioning and leads them to perform below their true abilities. Here, we present a protocol that highlights simple but efficient interventions to alleviate this age-based stereotype threat effect. The first study showed that simply informing older participants about the presence of younger participants (threat condition) led older adults to underperform on a standardized memory test compared with younger participants, and that this performance difference was eliminated when the test was presented as age-fair (reduced-threat condition). The second study replicated these findings on short cognitive tests used to screen for predementia in clinical settings and showed that teaching older adults about stereotype threat inoculated them against its effects. These results provide useful recommendations about how to improve older adults' memory assessment both in Iab studies and in clinical settings.

Here, we present a protocol designed to show how negative aging stereotypes can impair memory performance of older adults during cognitive testing and how to reduce this deleterious effect. This method can help older people to perform at an optimal level during testing in both lab studies and clinical settings.

As life expectancy increases, aging has become a major health challenge, resulting in a huge effort to better discriminate between normal and pathological ...

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

In neuroimaging, functional magnetic resonance imaging (fMRI) measures the blood-oxygenation-level dependent (BOLD) signal in the brain. The degree of correlation of the BOLD signal in spatially independent regions of the brain defines the functional connectivity of those regions. During a cognitive fMRI task, a psychophysiological interaction (PPI) analysis can be used to examine changes in the functional connectivity during specific contexts defined by the cognitive task. An example of such a task is one that engages the memory system, asking participants to learn pairs of unrelated words (encoding) and recall the second word in a pair when presented with the first word (retrieval). In the present study, we used this type of associative memory task and a generalized PPI (gPPI) analysis to compare changes in hippocampal connectivity in older adults who are carriers of the Alzheimer's disease (AD) genetic risk factor apolipoprotein-E epsilon-4 (APOE&#949;4). Specifically, we show that the functional connectivity of subregions of the hippocampus changes during encoding and retrieval, the two active phases of the associative memory task. Context-dependent changes in functional connectivity of the hippocampus were significantly different in carriers of APOE&#949;4 compared to non-carriers. PPI analyses make it possible to examine changes in functional connectivity, distinct from univariate main effects, and to compare these changes across groups. Thus, a PPI analysis may reveal complex task effects in specific cohorts that traditional univariate methods do not capture. PPI analyses cannot, however, determine directionality or causality between functionally connected regions. Nevertheless, PPI analyses provide powerful means for generating specific hypotheses regarding functional relationships, which can be tested using causal models. As the brain is increasingly described in terms of connectivity and networks, PPI is an important method for analyzing fMRI task data that is in line with the current conception of the human brain.

Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

This manuscript describes how to implement a psychophysiological interaction analysis to reveal task-dependent changes in functional connectivity between a selected seed region and voxels in other regions of the brain. Psychophysiological interaction analysis is a popular method to examine task effects on brain connectivity, distinct from traditional univariate activation effects.

In neuroimaging, functional magnetic resonance imaging (fMRI) measures the blood-oxygenation-level dependent (BOLD) signal in the brain. The degree of ...

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior Cingulate Cortex (PCC) is a potential imaging marker for monitoring the progression of AD. Previous studies did not focus on the functional connectivity between the PCC and nodes in regions outside the DMN, but our study is an effort to explore these overlooked functional connections. For collecting data, we used functional Magnetic Resonance Imaging (fMRI) and Granger Causality Analysis (GCA). fMRI provides a non-invasive method for studying the dynamic interactions between the different brain regions. GCA is a statistical hypothesis test for determining whether one-time series is useful in forecasting another. In simple terms, it is judged by comparing the &#34;Known all the information on the last moment, the distribution of the probability of X at this time&#34; and the &#34;Known all the information on the last moment except Y, the distribution of the probability of X at this time&#34;, to determine whether there is a causal relationship between Y and X. This definition is based on the complete information source and stationary chronological sequence. The main step of this analysis is to use X and Y to establish the regression equation and draw a causal relationship by a hypothetical test. Since GCA can measure causal effects, we used it to investigate the anisotropy of the functional connectivity and explore the hub function of the PCC. Here, we screened 116 participants for MRI scanning, and after preprocessing the data obtained from neuroimaging, we used GCA to derive the causal relationship of each node. Finally, we concluded that the directed connection is significantly different between the Mild Cognitive Impairment (MCI) and AD groups, both from the PCC to the whole brain and from the whole brain to the PCC.

Based on resting-state functional magnetic resonance imaging with Granger causality analysis, we investigated the alterations in the directed functional connectivity between the posterior cingulate cortex and whole brain in patients with Alzheimer&#39;s Disease (AD), patients with Mild Cognitive Impairment (MCI), and healthy controls.

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior ...

Medicine

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been modified into many versions. With the development of digital technologies, TMT is now modified to a digitized version. The present study demonstrated digital TMT (dTMT) performed on a computer, and Walking TMT (WTMT) on the floor. Both revealed more information compared with the traditional version of TMT.

Here, we present a protocol to show how to perform two types of cognitive assessment tools derived from the paper-pencil version of the Trail Making Test.

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been ...

Dual-Task Stroop Paradigm for Detecting Cognitive Deficits in High-Functioning Stroke Patients

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task assessment has advantages for identifying cognitive deficits in high-functioning stroke patients and has been gradually applied in clinical assessment and cognitive training. Moreover, the Stroop paradigm has higher sensitivity and specificity for attentional assessment than conventional clinical cognitive assessment scales. Therefore, this study presents the dual-task assessment based on the Stroop paradigm to identify cognitive deficits in high-functioning stroke patients. This study demonstrates a single- and dual-task evaluation based on the Stroop paradigm and confirms its feasibility through case experiments and synchronized functional near-infrared spectroscopy evaluation. The Stroop reaction time and correct rate are used as the main indicators to evaluate the cognitive level of the subjects. This study protocol aims to provide new ideas to figure out the ceiling effect in general clinical assessment failure for high-functioning stroke patients.

Clinical assessment scales are notsensitive enough to cognitive dysfunction in high-functioning stroke patients. The dual-task paradigm presents advantages and potential in the assessment and cognitive training of cognitive dysfunction. The study here proposes a dual-task Stroop paradigm to identify cognitive dysfunction in high-functioning stroke patients.

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task ...

Transcranial Pulse Stimulation for Alzheimer's Patients

Transcranial pulse stimulation (TPS) is a noninvasive neuromodulation therapy with Conformit&#233; Europ&#233;enne (CE) marking for the treatment of Alzheimer's disease (AD). Initial pilot studies have demonstrated promising effects on cognitive function. This article focuses on the procedure for treating patients with AD using an MRI-guided, neuro-navigated TPS device. The protocol to be followed for this is described in detail, including the necessary procedures and device settings. A brief overview of the representative clinical results published to date is also provided. In addition to significant clinical improvements in cognition and affect, adverse events (AE) and possible adverse device events (ADE) are presented to provide safety data. Finally, the method is critically discussed. In the future, randomized controlled trials should be conducted to rule out any placebo effects. There is also currently a lack of long-term studies with a larger number of patients. Despite these unresolved questions, TPS has the potential as an adjunct treatment for Alzheimer's patients when used in a controlled, scientifically guided setting.

This article describes the procedure of transcranial pulse stimulation in patients with Alzheimer's disease. It discusses the indications, methodology, and future prospects in detail.

Transcranial pulse stimulation (TPS) is a noninvasive neuromodulation therapy with Conformit&#233; Europ&#233;enne (CE) marking for the treatment of ...

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451

Alzheimer&#39;s disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by cognitive dysfunction, decline in daily living abilities, and behavioral changes, imposing a significant economic and social burden worldwide. One of the primary pathological hallmarks of AD is the accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. Positron emission tomography/magnetic resonance imaging (PET/MRI) provides detailed structural and functional information along with specific protein distributions, making it an increasingly valuable tool for AD diagnosis and research. 18F-AV-1451 is a radiotracer specifically designed for tau protein detection in PET imaging of brain tissue. This study presents a detailed protocol for the radiosynthesis of 18F-AV-1451, patient preparation, PET/MRI image acquisition techniques, and its potential applications in AD evaluation. 18F-AV-1451 PET/MRI could aid neurologists in diagnosing AD, assessing disease severity, and gaining insights into its pathological mechanisms. In conclusion, this protocol provides a sensitive, comprehensive, and non-invasive approach for the evaluation of AD, offering valuable insights into disease progression and pathology.

This protocol describes the use of 18F-AV-1451 PET/MRI to reveal tau pathology and neurodegeneration, aiding neurologists in diagnosing Alzheimer&#39;s disease, assessing its severity, and gaining insights into its progression and underlying pathological mechanisms.

Alzheimer&#39;s disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by cognitive dysfunction, decline in daily living ...

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

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