研究背景與目的：時間感知為一種主觀時間體驗的認知能力，它主要牽涉到注意力、記憶、決策能力，是不可或缺的認知功能。過去研究顯示，與認知未受損的對照組相比，阿茲海默失智症 (Alzheimer's dementia, AD) 病人有時間感知缺陷；但關於路易氏體失智症 (dementia with Lewy bodies, DLB) 病人的時間感知相關研究較少。如果能了解失智症前驅期階段的時間感知是否已有缺陷，將有助於未來理解這兩種失智症的病徵。因此本研究的目的在於探討前驅期阿茲海默失智症 (prodromal AD, prAD) 及前驅期路易氏體失智症 (prodromal DLB, prDLB) 時間感知的差異性。
研究方法：本研究邀請prAD、prDLB病人以及正常控制組 (CU) 參與研究。先施測神經心理測驗，再進行兩項時間感知測驗：口頭預估測驗及時間間隔製造測驗。了解三組對時間的準確度 (accuracy)、精密度 (precision) 以及高、低估時間的傾向，比較各組時間感知能力的差異。
研究結果：總共41位prAD、30位prDLB和37位CU完成了這項研究。在口頭預估測驗中，9秒 (F =4.14，p = 0.019) 以及27秒 (F = 4.21，p = 0.017) 的離散係數 (CV) 是prAD顯著高於CU組，顯示prAD組較CU組精密度差。時間間隔製造測驗中，主觀時間單位 (STU) 10秒 (F = 4.34，p = 0.015) 以及30秒 (F = 4.45，p = 0.014) 時間間隔是prAD顯著低於prDLB組，顯示prAD組較傾向高估時間，prDLB組較傾向低估時間。
結論：prAD表現出對時間的不精密和高估時間間隔的傾向。然而，三組之間的準確度沒有顯著差異，推測這兩個前驅期失智症的臨床和病理嚴重程度變異度較大，部分病人的時間感知準確度尚未受到影響。

Time perception is a subjective evaluation of time passing. Previous studies have shown that patients with Alzheimer's dementia (AD) have time perception deficits, while only a few studies explored time perception on patients with Dementia with Lewy bodies (DLB). Knowing the differences in time perception between prodromal AD (prAD) and prodromal DLB’s (prDLB) might be helpful for future understanding of these two dementias. PrAD, prDLB, and cognitive unimpaired control (CU) were recruited. Verbal estimation task and time interval production task were used to measure the accuracy, precision, and the tendency to overestimate and underestimate about time perception. Compared with CU, prAD showed the imprecision of time perception; and compared with prDLB, prAD had tendency of overestimate of time. No difference was found in accuracy among the three groups. It is speculated that the clinical and pathological severity of the two prodromal dementia stages may be relatively extensive, some patients have not yet had their time perception’s accuracy affected.

白明奇 (2018). 松鼠之家：失智症大地：遠流.

台灣失智症協會 (2021)。認識失智症。取自http://www.tada2002.org.tw/About/IsntDementia

Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., . . . Phelps, C. H. (2011). 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. Alzheimers Dement, 7(3), 270-279. doi:10.1016/j.jalz.2011.03.008

Angrilli, A., Cherubini, P., Pavese, A., & Mantredini, S. (1997). The influence of affective factors on time perception. Percept Psychophys, 59(6), 972-982. doi:10.3758/bf03205512

Battelli, L., Walsh, V., Pascual-Leone, A., & Cavanagh, P. (2008). The ‘when’ parietal pathway explored by lesion studies. Current Opinion in Neurobiology, 18(2), 120-126. doi:https://doi.org/10.1016/j.conb.2008.08.004

Bindra, D., & Waksberg, H. (1956). Methods and terminology in studies of time estimation. Psychological Bulletin, 53(2), 155.

Breitve, M. H., Hynninen, M. J., Brønnick, K., Chwiszczuk, L. J., Auestad, B. H., Aarsland, D., & Rongve, A. (2016). A longitudinal study of anxiety and cognitive decline in dementia with Lewy bodies and Alzheimer’s disease. Alzheimer's research & therapy, 8(1), 1-6.

Carrasco, M. C., Guillem, M. J., & Redolat, R. (2000). Estimation of short temporal intervals in Alzheimer's disease. Exp Aging Res, 26(2), 139-151. doi:10.1080/036107300243605

Church, R. M. (1984). Properties of the internal clock. Ann N Y Acad Sci, 423, 566-582. doi:10.1111/j.1749-6632.1984.tb23459.x

Colloby, S. J., O'Brien, J. T., & Taylor, J. P. (2014). Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimer׳s disease: A VBM-DARTEL study. Psychiatry Res, 223(3), 187-191. doi:10.1016/j.pscychresns.2014.06.006

Cotta Ramusino, M., Altomare, D., Bacchin, R., Ingala, S., Bnà, C., Bonetti, M., . . . Boccardi, M. (2019). Medial temporal lobe atrophy and posterior atrophy scales normative values. NeuroImage: Clinical, 24, 101936. doi:https://doi.org/10.1016/j.nicl.2019.101936

Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44(12), 2308-2308.

Davydenko, M., & Peetz, J. (2017). Time grows on trees: The effect of nature settings on time perception. Journal of Environmental Psychology, 54, 20-26. doi:https://doi.org/10.1016/j.jenvp.2017.09.003

Devanand, D. P., Pradhaban, G., Liu, X., Khandji, A., De Santi, S., Segal, S., . . . de Leon, M. J. (2007). Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology, 68(11), 828-836. doi:10.1212/01.wnl.0000256697.20968.d7

Droit‐Volet, S., Brunot, S., & Niedenthal, P. (2004). BRIEF REPORT Perception of the duration of emotional events. Cognition and Emotion, 18(6), 849-858.

El Haj, M., & Kapogiannis, D. (2016). Time distortions in Alzheimer's disease: a systematic review and theoretical integration. NPJ Aging Mech Dis, 2, 16016. doi:10.1038/npjamd.2016.16

El Haj, M., Omigie, D., & Moroni, C. (2014). Time reproduction during high and low attentional tasks in Alzheimer's Disease. "A watched kettle never boils". Brain Cogn, 88, 1-5. doi:10.1016/j.bandc.2014.04.002

Fierro, B., Palermo, A., Puma, A., Francolini, M., Panetta, M. L., Daniele, O., & Brighina, F. (2007). Role of the cerebellum in time perception: a TMS study in normal subjects. J Neurol Sci, 263(1-2), 107-112. doi:10.1016/j.jns.2007.06.033

Fontes, R., Ribeiro, J., Gupta, D. S., Machado, D., Lopes-Júnior, F., Magalhães, F., . . . Teixeira, S. (2016). Time Perception Mechanisms at Central Nervous System. Neurol Int, 8(1), 5939. doi:10.4081/ni.2016.5939

Gable, P. A., & Poole, B. D. (2012). Time flies when you're having approach-motivated fun: effects of motivational intensity on time perception. Psychol Sci, 23(8), 879-886. doi:10.1177/0956797611435817

Gooch, C. M., Wiener, M., Wencil, E. B., & Coslett, H. B. (2010). Interval timing disruptions in subjects with cerebellar lesions. Neuropsychologia, 48(4), 1022-1031. doi:10.1016/j.neuropsychologia.2009.11.028

Grondin, S. (2010). Timing and time perception: a review of recent behavioral and neuroscience findings and theoretical directions. Atten Percept Psychophys, 72(3), 561-582. doi:10.3758/app.72.3.561

Harrington, D. L., Lee, R. R., Boyd, L. A., Rapcsak, S. Z., & Knight, R. T. (2004). Does the representation of time depend on the cerebellum? Effect of cerebellar stroke.
Brain, 127(Pt 3), 561-574. doi:10.1093/brain/awh065

Hayashi, M. J., Kanai, R., Tanabe, H. C., Yoshida, Y., Carlson, S., Walsh, V., & Sadato, N. (2013). Interaction of numerosity and time in prefrontal and parietal cortex. J Neurosci, 33(3), 883-893. doi:10.1523/jneurosci.6257-11.2013

Heys, J. G., & Dombeck, D. A. (2018). Evidence for a subcircuit in medial entorhinal cortex representing elapsed time during immobility. Nat Neurosci, 21(11), 1574-1582. doi:10.1038/s41593-018-0252-8

Huang, S. H., Chang, C. C., Lui, C. C., Chen, N. C., Lee, C. C., Wang, P. W., & Jiang, C. F. (2015). Cortical metabolic and nigrostriatal abnormalities associated with clinical stage-specific dementia with Lewy bodies. Clin Nucl Med, 40(1), 26-31. doi:10.1097/rlu.0000000000000620

Ivry, R. B. (1996). The representation of temporal information in perception and motor control. Curr Opin Neurobiol, 6(6), 851-857. doi:10.1016/s0959-4388(96)80037-7

Ivry, R. B., Keele, S. W., & Diener, H. C. (1988). Dissociation of the lateral and medial cerebellum in movement timing and movement execution. Exp Brain Res, 73(1), 167-180. doi:10.1007/bf00279670

Jacobs, H. I. L., Hopkins, D. A., Mayrhofer, H. C., Bruner, E., van Leeuwen, F. W., Raaijmakers, W., & Schmahmann, J. D. (2018). The cerebellum in Alzheimer's disease: evaluating its role in cognitive decline. Brain, 141(1), 37-47. doi:10.1093/brain/awx194

Kitamura, T., & Kumar, R. (1983). Time estimation and time production in depressive patients. Acta Psychiatr Scand, 68(1), 15-21. doi:10.1111/j.1600-0447.1983.tb06976.x

Koch, G., Oliveri, M., Carlesimo, G. A., & Caltagirone, C. (2002). Selective deficit of time perception in a patient with right prefrontal cortex lesion. Neurology, 59(10), 1658-1659. doi:10.1212/01.wnl.0000032504.45792.8f

Lesimple, B., Dieudonné, B., Campillo-Gimenez, B., Verny, M., & Giannopulu, I. (2016). Time perception in patients with dementia with Lewy bodies. Geriatr Psychol Neuropsychiatr Vieil, 14(2), 213-220. doi:10.1684/pnv.2016.0604

Lui, M. A., Penney, T. B., & Schirmer, A. (2011). Emotion effects on timing: attention versus pacemaker accounts. PLoS One, 6(7), e21829. doi:10.1371/journal.pone.0021829

McKeith, I. G. (2004). Dementia with Lewy bodies. Dialogues Clin Neurosci, 6(3), 333-341.

McKeith, I. G., Ferman, T. J., Thomas, A. J., Blanc, F., Boeve, B. F., Fujishiro, H., . . . Tiraboschi, P. (2020). Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology, 94(17), 743-755. doi:10.1212/wnl.0000000000009323

Mimura, M., Kinsbourne, M., & O'Connor, M. (2000). Time estimation by patients with frontal lesions and by Korsakoff amnesics. J Int Neuropsychol Soc, 6(5), 517-528. doi:10.1017/s1355617700655017

Mioni, G., Stablum, F., McClintock, S. M., & Grondin, S. (2014). Different methods for reproducing time, different results. Attention, Perception, & Psychophysics, 76(3), 675-681. doi:10.3758/s13414-014-0625-3

Moskowitz, G. B., Olcaysoy Okten, I., & Gooch, C. M. (2015). On Race and Time. Psychol Sci, 26(11), 1783-1794. doi:10.1177/0956797615599547

Nichelli, P., Venneri, A., Molinari, M., Tavani, F., & Grafman, J. (1993). Precision and accuracy of subjective time estimation in different memory disorders. Brain Res Cogn Brain Res, 1(2), 87-93. doi:10.1016/0926-6410(93)90014-v

Norton, M. C., Smith, K. R., Østbye, T., Tschanz, J. T., Corcoran, C., Schwartz, S., . . . Investigators, f. t. C. C. (2010). Greater Risk of Dementia When Spouse Has Dementia? The Cache County Study. Journal of the American Geriatrics Society, 58(5), 895-900. doi:https://doi.org/10.1111/j.1532-5415.2010.02806.x

Noulhiane, M., Pouthas, V., Hasboun, D., Baulac, M., & Samson, S. (2007). Role of the medial temporal lobe in time estimation in the range of minutes. Neuroreport, 18(10), 1035-1038. doi:10.1097/WNR.0b013e3281668be1

Ogden, R. S., Wearden, J. H., & Montgomery, C. (2014). The differential contribution of executive functions to temporal generalisation, reproduction and verbal estimation. Acta Psychol (Amst), 152, 84-94. doi:10.1016/j.actpsy.2014.07.014

Pai, M. C., & Jan, S. S. (2020). Have I Been Here? Sense of Location in People With Alzheimer's Disease. Front Aging Neurosci, 12, 582525. doi:10.3389/fnagi.2020.582525

Papagno, C., Allegra, A., & Cardaci, M. (2004). Time estimation in Alzheimer's disease and the role of the central executive. Brain Cogn, 54(1), 18-23. doi:10.1016/s0278-2626(03)00237-9

Pastor, M. A., Artieda, J., Jahanshahi, M., & Obeso, J. A. (1992). Time estimation and reproduction is abnormal in Parkinson's disease. Brain, 115 Pt 1, 211-225. doi:10.1093/brain/115.1.211

Rao, S. M., Mayer, A. R., & Harrington, D. L. (2001). The evolution of brain activation during temporal processing. Nature Neuroscience, 4(3), 317. doi:10.1038/85191

Rueda, A. D., & Schmitter-Edgecombe, M. (2009). Time estimation abilities in mild cognitive impairment and Alzheimer's disease. Neuropsychology, 23(2), 178-188. doi:10.1037/a0014289

Sadiq, D., Whitfield, T., Lee, L., Stevens, T., Costafreda, S., & Walker, Z. (2017). Prodromal Dementia with Lewy Bodies and Prodromal Alzheimer's Disease: A Comparison of the Cognitive and Clinical Profiles. J Alzheimers Dis, 58(2), 463-470. doi:10.3233/jad-161089

Sarigiannidis, I., Grillon, C., Ernst, M., Roiser, J. P., & Robinson, O. J. (2020). Anxiety makes time pass quicker while fear has no effect. Cognition, 197, 104116. doi:10.1016/j.cognition.2019.104116

Schmitter-Edgecombe, M., & Rueda, A. D. (2008). Time estimation and episodic memory following traumatic brain injury. Journal of Clinical and Experimental Neuropsychology, 30(2), 212-223. doi:10.1080/13803390701363803

Wittmann, M., Simmons, A. N., Aron, J. L., & Paulus, M. P. (2010). Accumulation of neural activity in the posterior insula encodes the passage of time. Neuropsychologia, 48(10), 3110-3120. doi:https://doi.org/10.1016/j.neuropsychologia.2010.06.023