The overlap between vascular disease and Alzheimer’s disease – lessons from pathology

BMC Medicine

Kurt A Jellinger²  Johannes Attems¹ 

[1] Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK;Institute of Clinical Neurobiology, Medical University Vienna, Kenyongasse 18, Vienna, 1070, Austria

关键词: White matter lesions;    Small vessel disease;    Microinfarcts;    Lacunes;    Cognitive impairment;    Cerebral amyloid angiopathy;    Cerebrovascular lesions;    Alzheimer’s disease;   

Others  :  1118227
DOI  :  10.1186/s12916-014-0206-2

 received in 2014-07-01, accepted in 2014-10-07,  发布年份 2014

【 摘 要 】

Recent epidemiological and clinico-pathological data indicate considerable overlap between cerebrovascular disease (CVD) and Alzheimer’s disease (AD) and suggest additive or synergistic effects of both pathologies on cognitive decline. The most frequent vascular pathologies in the aging brain and in AD are cerebral amyloid angiopathy and small vessel disease. Up to 84% of aged subjects show morphological substrates of CVD in addition to AD pathology. AD brains with minor CVD, similar to pure vascular dementia, show subcortical vascular lesions in about two-thirds, while in mixed type dementia (AD plus vascular dementia), multiple larger infarcts are more frequent. Small infarcts in patients with full-blown AD have no impact on cognitive decline but are overwhelmed by the severity of Alzheimer pathology, while in early stages of AD, cerebrovascular lesions may influence and promote cognitive impairment, lowering the threshold for clinically overt dementia. Further studies are warranted to elucidate the many hitherto unanswered questions regarding the overlap between CVD and AD as well as the impact of both CVD and AD pathologies on the development and progression of dementia.

【 授权许可】

   
2014 Attems and Jellinger; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Petrovitch H, Ross GW, Steinhorn SC, Abbott RD, Markesberry W, Davis DG, Nelson J, Hardman J, Masaki KH, Vogt MR, Launer LJ, White LR: AD lesions and infarcts in demented and no-demented Japanese-American men. Ann Neurol 2005, 57:98-103.
• [2]Jellinger KA: The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol 2007, 113:349-388.
• [3]Jellinger KA: The enigma of mixed dementia. Alzheimers Dement 2007, 3:40-53.
• [4]Schneider JA, Arvanitakis Z, Bang W, Bennett DA: Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007, 69:2197-2204.
• [5]Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ: Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 2013, 136:2697-2706.
• [6]Chui HC, Zarow C, Mack WJ, Ellis WG, Zheng L, Jagust WJ, Mungas D, Reed BR, Kramer JH, Decarli CC, Weiner MW, Vinters HV: Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 2006, 60:677-687.
• [7]Giannakopoulos P, Gold G, Kovari E, von Gunten A, Imhof A, Bouras C, Hof PR: Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 2007, 113:1-12.
• [8]Esiri MM, Joachim C, Sloan C, Christie S, Agacinski G, Bridges LR, Wilcock GK, Smith AD: Cerebral subcortical small vessel disease in subjects with pathologically confirmed Alzheimer disease: a clinicopathologic study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). Alzheimer Dis Assoc Disord 2014, 28:30-35.
• [9]Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alzheimer disease. Nun Study JAMA 1997, 277:813-817.
• [10]Schneider JA, Aggarwal NT, Barnes L, Boyle P, Bennett DA: The neuropathology of older persons with and without dementia from community versus clinic cohorts. J Alzheimers Dis 2009, 18:691-701.
• [11]Schneider JA, Wilson RS, Cochran EJ, Bienias JL, Arnold SE, Evans DA, Bennett DA: Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 2003, 60:1082-1088.
• [12]Jellinger KA: Prevalence and impact of cerebrovascular lesions in Alzheimer and Lewy body diseases. Neurodegener Dis 2010, 7:112-115.
• [13]Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD: Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet 1999, 354:919-920.
• [14]Sonnen JA, Larson EB, Crane PK, Haneuse S, Li G, Schellenberg GD, Craft S, Leverenz JB, Montine TJ: Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 2007, 62:406-413.
• [15]Troncoso JC, Zonderman AB, Resnick SM, Crain B, Pletnikova O, O’Brien RJ: Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann Neurol 2008, 64:168-176.
• [16]Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S: Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011, 42:2672-2713.
• [17]Jellinger KA: Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 2002, 109:813-836.
• [18]Strozyk D, Dickson DW, Lipton RB, Katz M, Derby CA, Lee S, Wang C, Verghese J: Contribution of vascular pathology to the clinical expression of dementia. Neurobiol Aging 2010, 31:1710-1720.
• [19]Launer LJ, Petrovitch H, Ross GW, Markesbery W, White LR: AD brain pathology: vascular origins? Results from the HAAS autopsy study. Neurobiol Aging 2008, 29:1587-1590.
• [20]Costanza A, Xekardaki A, Kovari E, Gold G, Bouras C, Giannakopoulos P: Microvascular burden and Alzheimer-type lesions across the age spectrum. J Alzheimers Dis 2012, 32:643-652.
• [21]Esiri MM, Chance SA: Cognitive reserve, cortical plasticity and resistance to Alzheimer’s disease. Alzheimers Res Ther 2012, 4:7.
• [22]Kalaria RN: The role of cerebral ischemia in Alzheimer’s disease. Neurobiol Aging 2000, 21:321-330.
• [23]Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ: Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol (Berl) 2002, 103:481-487.
• [24]Kalaria RN: Risk factors and neurodegenerative mechanisms in stroke related dementia. Panminerva Med 2012, 54:139-148.
• [25]Bennett DA, Wilson RS, Boyle PA, Buchman AS, Schneider JA: Relation of neuropathology to cognition in persons without cognitive impairment. Ann Neurol 2012, 72:599-609.
• [26]Lo RY, Jagust WJ: Vascular burden and Alzheimer disease pathologic progression. Neurology 2012, 79:1349-1355.
• [27]O’Brien TJ, Wadley V, Nicholas AP, Stover NP, Watts R, Griffith HR: The contribution of executive control on verbal-learning impairment in patients with Parkinson’s disease with dementia and Alzheimer’s disease. Arch Clin Neuropsychol 2009, 24:237-244.
• [28]Snyder HM, Corriveau RA, Craft S, Faber JE, Greenberg S, Knopman D, Lamb BT, Montine TJ, Nedergaard M, Schaffer CB, Schneider JA, Wellington C, Wilcock DM, Zipfel GJ, Zlokovic B, Bain LS, Bosetti F, Galis ZS, Koroshetz W, Carrillo MC: Vascular contributions to cognitive impairment and dementia including Alzheimer’s disease.Alzheimers Dement 2015. In press.
• [29]Stephan BC, Matthews FE, Ma B, Muniz G, Hunter S, Davis D, McKeith IG, Foster G, Ince PG, Brayne C: Alzheimer and vascular neuropathological changes associated with different cognitive States in a non-demented sample. J Alzheimers Dis 2012, 29:309-318.
• [30]Casserly I, Topol E: Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet 2004, 363:1139-1146.
• [31]Barnes DE, Yaffe K: The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 2011, 10:819-828.
• [32]Jellinger KA: Morphologic diagnosis of “vascular dementia” – a critical update. J Neurol Sci 2008, 270:1-12.
• [33]Meng X-F, Yu J-T, Wang H-F, Tan M-S, Wang C, Tan C-C, Tan L: Midlife vascular risk factors and the risk of Alzheimer's disease: a systematic review and meta-analysis.J Alzheimers Dis 2014. in print: doi:10.3233/JAD-140954.
• [34]Elias MF, Sullivan LM, D’Agostino RB, Elias PK, Jacques PF, Selhub J, Seshadri S, Au R, Beiser A, Wolf PA: Homocysteine and cognitive performance in the Framingham offspring study: age is important. Am J Epidemiol 2005, 162:644-653.
• [35]Toledo JB, Toledo E, Weiner MW, Jack CR Jr, Jagust W, Lee VM, Shaw LM, Trojanowski JQ: Cardiovascular risk factors, cortisol, and amyloid-beta deposition in Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement 2012, 8:483-489.
• [36]Polidori MC, Pientka L, Mecocci P: A review of the major vascular risk factors related to Alzheimer’s disease. J Alzheimers Dis 2012, 32:521-530.
• [37]Kling MA, Trojanowski JQ, Wolk DA, Lee VM, Arnold SE: Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimers Dement 2013, 9:76-92.
• [38]Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M: Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 2010, 75:1195-1202.
• [39]Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, Stern Y: Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol 2009, 66:343-348.
• [40]Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J: Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006, 5:735-741.
• [41]Mielke MM, Rosenberg PB, Tschanz J, Cook L, Corcoran C, Hayden KM, Norton M, Rabins PV, Green RC, Welsh-Bohmer KA, Breitner JC, Munger R, Lyketsos CG: Vascular factors predict rate of progression in Alzheimer disease. Neurology 2007, 69:1850-1858.
• [42]Qiu C, Xu W, Winblad B, Fratiglioni L: Vascular risk profiles for dementia and Alzheimer’s disease in very old people: a population-based longitudinal study. J Alzheimers Dis 2010, 20:293-300.
• [43]Richardson K, Stephan BC, Ince PG, Brayne C, Matthews FE, Esiri MM: The neuropathology of vascular disease in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Curr Alzheimer Res 2012, 9:687-696.
• [44]Eriksson UK, Bennet AM, Gatz M, Dickman PW, Pedersen NL: Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia. Alzheimer Dis Assoc Disord 2010, 24:213-219.
• [45]Jellinger KA: Small concomitant cerebrovascular lesions are not important for cognitive decline in severe Alzheimer disease. Arch Neurol 2001, 58:520-521.
• [46]Mungas D, Jagust WJ, Reed BR, Kramer JH, Weiner MW, Schuff N, Norman D, Mack WJ, Willis L, Chui HC: MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer’s disease. Neurology 2001, 57:2229-2235.
• [47]Jellinger KA, Attems J: Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis 2010, 21:1283-1293.
• [48]Rincon F, Wright CB: Current pathophysiological concepts in cerebral small vessel disease. Front Aging Neurosci 2014, 6:24.
• [49]Goulding JM, Signorini DF, Chatterjee S, Nicoll JA, Stewart J, Morris R, Lammie GA: Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia. J Neurol Neurosurg Psychiatry 1999, 67:654-657.
• [50]Arvanitakis Z, Leurgans SE, Barnes LL, Bennett DA, Schneider JA: Microinfarct pathology, dementia, and cognitive systems. Stroke 2011, 42:722-727.
• [51]Bennett DA, Wilson RS, Arvanitakis Z, Boyle PA, de Toledo-Morrell L, Schneider JA: Selected findings from the religious orders study and rush memory and aging project. J Alzheimers Dis 2013, 33:S397-S403.
• [52]Crystal H, Dickson D: Cerebral infarcts in patients with autopsy proven Alzheimer’s disease. Neurobiol Aging 2002, 23:207.
• [53]Esiri MM, Wilcock GK, Morris JH: Neuropathological assessment of the lesions of significance in vascular dementia. J Neurol Neurosurg Psychiatry 1997, 63:749-753.
• [54]Lee JH, Olichney JM, Hansen LA, Hofstetter CR, Thal LJ: Small concomitant vascular lesions do not influence rates of cognitive decline in patients with Alzheimer disease. Arch Neurol 2000, 57:1474-1479.
• [55]Smallwood A, Oulhaj A, Joachim C, Christie S, Sloan C, Smith AD, Esiri M: Cerebral subcortical small vessel disease and its relation to cognition in elderly subjects: a pathological study in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. Neuropathol Appl Neurobiol 2012, 38:337-343.
• [56]Kalaria RN: Advances in molecular genetics and pathology of cerebrovascular disorders. Trends Neurosci 2001, 24:392-400.
• [57]Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, Vitek MP, Hovanesian V, Stopa EG: Microvascular injury and blood–brain barrier leakage in Alzheimer’s disease. Neurobiol Aging 2007, 28:977-986.
• [58]Nagata K, Takano D, Yamazaki T, Maeda T, Satoh Y, Nakase T, Ikeda Y: Cerebrovascular lesions in elderly Japanese patients with Alzheimer’s disease. J Neurol Sci 2012, 322:87-91.
• [59]Launer LJ, Hughes TM, White LR: Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann Neurol 2011, 70:774-780.
• [60]Sinka L, Kovari E, Gold G, Hof PR, Herrmann FR, Bouras C, Giannakopoulos P: Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old. J Neuropathol Exp Neurol 2010, 69:1247-1255.
• [61]Utter S, Tamboli IY, Walter J, Upadhaya AR, Birkenmeier G, Pietrzik CU, Ghebremedhin E, Thal DR: Cerebral small vessel disease-induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta-protein in perivascular astrocytes. J Neuropathol Exp Neurol 2008, 67:842-856.
• [62]Garcia-Alloza M, Gregory J, Kuchibhotla KV, Fine S, Wei Y, Ayata C, Frosch MP, Greenberg SM, Bacskai BJ: Cerebrovascular lesions induce transient beta-amyloid deposition. Brain 2011, 134:3697-3707.
• [63]Lee CW, Shih YH, Kuo YM: Cerebrovascular pathology and amyloid plaque formation in Alzheimer’s disease. Curr Alzheimer Res 2013, 11:4-10.
• [64]Hawkes CA, Sullivan PM, Hands S, Weller RO, Nicoll JA, Carare RO: Disruption of arterial perivascular drainage of amyloid-beta from the brains of mice expressing the human APOE epsilon4 allele. PLoS One 2012, 7:e41636.
• [65]Hawkes CA, Carare RO, Weller RO: Amyloid and tau in the brain in sporadic Alzheimer’s disease: defining the chicken and the egg. Acta Neuropathol 2014, 127:617-618.
• [66]Lewis H, Beher D, Cookson N, Oakley A, Piggott M, Morris CM, Jaros E, Perry R, Ince P, Kenny RA, Ballard CG, Shearman MS, Kalaria RN: Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia. Neuropathol Appl Neurobiol 2006, 32:103-118.
• [67]Hulette CM, Ervin JF, Edmonds Y, Antoine S, Stewart N, Szymanski MH, Hayden KM, Pieper CF, Burke JR, Welsh-Bohmer KA: Cerebrovascular smooth muscle actin is increased in nondemented subjects with frequent senile plaques at autopsy: implications for the pathogenesis of Alzheimer disease. J Neuropathol Exp Neurol 2009, 68:417-424.
• [68]de la Torre JC: Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002, 33:1152-1162.
• [69]Shi J, Perry G, Smith MA, Friedland RP: Vascular abnormalities: the insidious pathogenesis of Alzheimer’s disease. Neurobiol Aging 2000, 21:357-361.
• [70]de la Torre JC, Stefano GB: Evidence that Alzheimer’s disease is a microvascular disorder: the role of constitutive nitric oxide. Brain Res Brain Res Rev 2000, 34:119-136.
• [71]Kudo T, Imaizumi K, Tanimukai H, Katayama T, Sato N, Nakamura Y, Tanaka T, Kashiwagi Y, Jinno Y, Tohyama M, Takeda M: Are cerebrovascular factors involved in Alzheimer’s disease? Neurobiol Aging 2000, 21:215-224.
• [72]Schmidt R, Schmidt H, Fazekas F: Vascular risk factors in dementia. J Neurol 2000, 247:81-87.
• [73]Farkas E, Luiten PG: Cerebral microvascular pathology in aging and Alzheimer’s disease. Prog Neurobiol 2001, 64:575-611.
• [74]Brown WR, Moody DM, Challa VR, Thore CR: Cerebrovascular pathology in Alzheimer disease. In Research and Practice in Alzheimer’s Disease. Edited by Vellas B, Fitten LJ, Winblad B, Feldman H, Grundman M, Giacobini E. Serdi Publications, Springer, Paris, New York; 2001:76-81.
• [75]Miklossy J: Cerebral hypoperfusion induces cortical watershed microinfarcts which may further aggravate cognitive decline in Alzheimer’s disease. Neurol Res 2003, 25:605-610.
• [76]Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS: Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005, 64:834-841.
• [77]Gold G, Giannakopoulos P, Herrmann FR, Bouras C, Kovari E: Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 2007, 130:2830-2836.
• [78]Zekry D, Duyckaerts C, Belmin J, Geoffre C, Herrmann F, Moulias R, Hauw JJ: The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy. Neurobiol Aging 2003, 24:213-219.
• [79]Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR: Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 2007, 66:1136-1146.
• [80]Nelson PT, Pious NM, Jicha GA, Wilcock DM, Fardo DW, Estus S, Rebeck GW: APOE-epsilon2 and APOE-epsilon4 correlate with increased amyloid accumulation in cerebral vasculature. J Neuropathol Exp Neurol 2013, 72:708-715.
• [81]Iadecola C: The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 2010, 120:287-296.
• [82]Heyman A, Fillenbaum G, Welsh-Bohmer K, Gearing M, Mirra SS, Mohs RC, Peterson BL, Pieper CF: Cerebral infarcts in patients with autopsy-proven Alzheimer’s disease, CERAD, Part XVIII. Neurology 1998, 51:159-162.
• [83]Riekse RG, Leverenz JB, McCormick W, Bowen JD, Teri L, Nochlin D, Simpson K, Eugenio C, Larson EB, Tsuang D: Effect of vascular lesions on cognition in Alzheimer’s disease: a community-based study. J Am Geriatr Soc 2004, 52:1442-1448.
• [84]Zlokovic BV: Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci 2005, 28:202-208.
• [85]Zlokovic BV: Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011, 12:723-738.
• [86]Du AT, Schuff N, Chao LL, Kornak J, Ezekiel F, Jagust WJ, Kramer JH, Reed BR, Miller BL, Norman D, Chui HC, Weiner MW: White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy. Neurobiol Aging 2005, 26:553-559.
• [87]Grinberg LT, Thal DR: Vascular pathology in the aged human brain. Acta Neuropathol 2010, 119:277-290.
• [88]Attems J, Yamaguchi H, Saido TC, Thal DR: Capillary CAA and perivascular Abeta-deposition: two distinct features of Alzheimer’s disease pathology. J Neurol Sci 2010, 299:155-162.
• [89]Attems J, Jellinger K, Thal DR, Van Nostrand W: Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2011, 37:75-93.
• [90]Attems J, Jellinger KA, Lintner F: Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol (Berl) 2005, 110:222-231.
• [91]Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM: Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009, 8:165-174.
• [92]Pezzini A, Del Zotto E, Volonghi I, Giossi A, Costa P, Padovani A: Cerebral amyloid angiopathy: a common cause of cerebral hemorrhage. Curr Med Chem 2009, 16:2498-2513.
• [93]Jellinger KA, Lauda F, Attems J: Sporadic cerebral amyloid angiopathy is not a frequent cause of spontaneous brain hemorrhage. Eur J Neurol 2007, 14:923-928.
• [94]Attems J, Lauda F, Jellinger KA: Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. J Neurol 2008, 255:70-76.
• [95]Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, Neal B, Chalmers J: Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke 2010, 41:394-396.
• [96]Gregoire SM, Charidimou A, Gadapa N, Dolan E, Antoun N, Peeters A, Vandermeeren Y, Laloux P, Baron JC, Jager HR, Werring DJ: Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain 2011, 134:2376-2386.
• [97]Chen YW, Gurol ME, Rosand J, Viswanathan A, Rakich SM, Groover TR, Greenberg SM, Smith EE: Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy. Neurology 2006, 67:83-87.
• [98]Okamoto Y, Ihara M, Fujita Y, Ito H, Takahashi R, Tomimoto H: Cortical microinfarcts in Alzheimer’s disease and subcortical vascular dementia. Neuroreport 2009, 20:990-996.
• [99]Soontornniyomkij V, Lynch MD, Mermash S, Pomakian J, Badkoobehi H, Clare R, Vinters HV: Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy. Brain Pathol 2010, 20:459-467.
• [100]Kovari E, Herrmann FR, Hof PR, Bouras C: The relationship between cerebral amyloid angiopathy and cortical microinfarcts in brain ageing and Alzheimer’s disease. Neuropathol Appl Neurobiol 2013, 39:498-509.
• [101]Matthews FE, Jagger C, Miller LL, Brayne C: Education differences in life expectancy with cognitive impairment. J Gerontol A Biol Sci Med Sci 2009, 64:125-131.
• [102]Charidimou A, Peeters AP, Jager R, Fox Z, Vandermeeren Y, Laloux P, Baron JC, Werring DJ: Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy. Neurology 2013, 81:1666-1673.
• [103]Charidimou A, Jager RH, Fox Z, Peeters A, Vandermeeren Y, Laloux P, Baron JC, Werring DJ: Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013, 81:626-632.
• [104]Charidimou A, Meegahage R, Fox Z, Peeters A, Vandermeeren Y, Laloux P, Baron JC, Jager HR, Werring DJ: Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry 2013, 84:624-629.
• [105]Knudsen KA, Rosand J, Karluk D, Greenberg SM: Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001, 56:537-539.
• [106]Gurol ME, Greenberg SM: A physiologic biomarker for cerebral amyloid angiopathy. Neurology 2013, 81:1650-1651.
• [107]Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, van Buchem MA, Bruckmann H, Greenberg SM: Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010, 74:1346-1350.
• [108]Schrag M, McAuley G, Pomakian J, Jiffry A, Tung S, Mueller C, Vinters HV, Haacke EM, Holshouser B, Kido D, Kirsch WM: Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol 2010, 119:291-302.
• [109]Viswanathan A, Greenberg SM: Cerebral amyloid angiopathy in the elderly. Ann Neurol 2011, 70:871-880.
• [110]Johnson KA, Gregas M, Becker JA, Kinnecom C, Salat DH, Moran EK, Smith EE, Rosand J, Rentz DM, Klunk WE, Mathis CA, Price JC, Dekosky ST, Fischman AJ, Greenberg SM: Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 2007, 62:229-234.
• [111]Greenberg SM, Grabowski T, Gurol ME, Skehan ME, Nandigam RN, Becker JA, Garcia-Alloza M, Prada C, Frosch MP, Rosand J, Viswanathan A, Smith EE, Johnson KA: Detection of isolated cerebrovascular beta-amyloid with Pittsburgh compound B. Ann Neurol 2008, 64:587-591.
• [112]Renard D, Castelnovo G, Wacongne A, Le Floch A, Thouvenot E, Mas J, Gabelle A, Labauge P, Lehmann S: Interest of CSF biomarker analysis in possible cerebral amyloid angiopathy cases defined by the modified Boston criteria. J Neurol 2012, 259:2429-2433.
• [113]Verbeek MM, Kremer BP, Rikkert MO, Van Domburg PH, Skehan ME, Greenberg SM: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009, 66:245-249.
• [114]de Jong D, Kremer BP, Olde Rikkert MG, Verbeek MM: Current state and future directions of neurochemical biomarkers for Alzheimer’s disease. Clin Chem Lab Med 2007, 45:1421-1434.
• [115]Pantoni L: Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010, 9:689-701.
• [116]Thal DR, Ghebremedhin E, Orantes M, Wiestler OD: Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 2003, 62:1287-1301.
• [117]Ortner M, Kurz A, Alexopoulos P, Auer F, Diehl-Schmid J, Drzezga A, Forster S, Forstl H, Perneczky R, Sorg C, Yousefi BH, Grimmer T: Small vessel disease, but neither amyloid load nor metabolic deficit, is dependent on age at onset in Alzheimer’s Disease.Biol Psychiatry 2014. In press.
• [118]Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM: Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke 2010, 41:450-454.
• [119]Duering M, Csanadi E, Gesierich B, Jouvent E, Herve D, Seiler S, Belaroussi B, Ropele S, Schmidt R, Chabriat H, Dichgans M: Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain 2013, 136:2717-2726.
• [120]Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, Enzinger C, Ropele S, Erkinjuntti T, Pantoni L, Scheltens P, Fazekas F, Jellinger K: Heterogeneity in age-related white matter changes. Acta Neuropathol 2011, 122:171-185.
• [121]Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O’Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge R, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, et al.: Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013, 12:822-838.
• [122]Cordonnier C, van der Flier WM: Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain 2011, 134:335-344.
• [123]Park JH, Seo SW, Kim C, Kim GH, Noh HJ, Kim ST, Kwak KC, Yoon U, Lee JM, Lee JW, Shin JS, Kim CH, Noh Y, Cho H, Kim HJ, Yoon CW, Oh SJ, Kim JS, Choe YS, Lee KH, Lee JH, Ewers M, Weiner MW, Werring DJ, Na DL: Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol 2013, 73:584-593.
• [124]Young VG, Halliday GM, Kril JJ: Neuropathologic correlates of white matter hyperintensities. Neurology 2008, 71:804-811.
• [125]Polvikoski TM, van Straaten EC, Barkhof F, Sulkava R, Aronen HJ, Niinisto L, Oinas M, Scheltens P, Erkinjuntti T, Kalaria RN: Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old. Neurology 2010, 75:2071-2078.
• [126]McAleese KE, Firbank M, Hunter D, Sun L, Hall R, Neal JW, Mann DM, Esiri M, Jellinger KA, O’Brien JT, Attems J: Magnetic resonance imaging of fixed post mortem brains reliably reflects subcortical vascular pathology of frontal, parietal and occipital white matter. Neuropathol Appl Neurobiol 2013, 39:485-497.
• [127]Piguet O, Double KL, Kril JJ, Harasty J, Macdonald V, McRitchie DA, Halliday GM: White matter loss in healthy ageing: a postmortem analysis. Neurobiol Aging 2009, 30:1288-1295.
• [128]Bell RD, Zlokovic BV: Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 2009, 118:103-113.
• [129]Topakian R, Barrick TR, Howe FA, Markus HS: Blood–brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry 2010, 81:192-197.
• [130]Wardlaw JM, Doubal F, Armitage P, Chappell F, Carpenter T, Munoz Maniega S, Farrall A, Sudlow C, Dennis M, Dhillon B: Lacunar stroke is associated with diffuse blood–brain barrier dysfunction. Ann Neurol 2009, 65:194-202.
• [131]Rosenberg GA: Neurological diseases in relation to the blood–brain barrier. J Cereb Blood Flow Metab 2012, 32:1139-1151.
• [132]Viggars AP, Wharton SB, Simpson JE, Matthews FE, Brayne C, Savva GM, Garwood C, Drew D, Shaw PJ, Ince PG: Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. Neurosci Lett 2011, 505:25-30.
• [133]Vermeer SE, Longstreth WT Jr, Koudstaal PJ: Silent brain infarcts: a systematic review. Lancet Neurol 2007, 6:611-619.
• [134]Thong JY, Hilal S, Wang Y, Soon HW, Dong Y, Collinson SL, Anh TT, Ikram MK, Wong TY, Venketasubramanian N, Chen C, Qiu A: Association of silent lacunar infarct with brain atrophy and cognitive impairment. J Neurol Neurosurg Psychiatry 2013, 84:1219-1225.
• [135]Thal DR, Griffin WS, de Vos RA, Ghebremedhin E: Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease. Acta Neuropathol 2008, 115:599-609.
• [136]Brundel M, de Bresser J, van Dillen JJ, Kappelle LJ, Biessels GJ: Cerebral microinfarcts: a systematic review of neuropathological studies. J Cereb Blood Flow Metab 2012, 32:425-436.
• [137]van Veluw SJ, Heringa SM, Kuijf HJ, Koek HL, Luijten PR, Biessels GJ: Cerebral cortical microinfarcts at 7 Tesla MRI in patients with early Alzheimer’s disease. J Alzheimers Dis 2013, 39:163-167.
• [138]Yarchoan M, Xie SX, Kling MA, Toledo JB, Wolk DA, Lee EB, Van Deerlin V, Lee VM, Trojanowski JQ, Arnold SE: Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 2012, 135:3749-3756.
• [139]Beach TG, Wilson JR, Sue LI, Newell A, Poston M, Cisneros R, Pandya Y, Esh C, Connor DJ, Sabbagh M, Walker DG, Roher AE: Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol 2007, 113:13-21.
• [140]Roher AE, Tyas SL, Maarouf CL, Daugs ID, Kokjohn TA, Emmerling MR, Garami Z, Belohlavek M, Sabbagh MN, Sue LI, Beach TG: Intracranial atherosclerosis as a contributing factor to Alzheimer’s disease dementia. Alzheimers Dement 2011, 7:436-444.
• [141]Honig LS, Kukull W, Mayeux R: Atherosclerosis and AD: analysis of data from the US National Alzheimer’s Coordinating Center. Neurology 2005, 64:494-500.
• [142]Luoto TM, Haikonen S, Haapasalo H, Goebeler S, Huhtala H, Erkinjuntti T, Karhunen PJ: Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer’s disease. Eur Neurol 2009, 62:93-98.
• [143]Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, O’Brien RJ: Atherosclerosis, dementia, and Alzheimer’s disease in the BLSA cohort. Ann Neurol 2010, 68:231-240.
• [144]Iadecola C: The pathobiology of vascular dementia. Neuron 2013, 80:844-866.
• [145]Jellinger KA: Challenges in the neuropathological diagnosis of dementias. Int J Neuropathol 2013, 1:8-52.
• [146]Jellinger KA: Pathogenesis and treatment of vascular cognitive impairment.Neurodeg Dis Management 2014. In press.
• [147]Jellinger KA, Attems J: Neuropathological evaluation of mixed dementia. J Neurol Sci 2007, 257:80-87.
• [148]Kalaria RN, Ballard C: Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999, 13:S115-S123.
• [149]Olichney JM, Ellis RJ, Katzman R, Sabbagh MN, Hansen L: Types of cerebrovascular lesions associated with severe cerebral amyloid angiopathy in Alzheimer’s disease. Ann N Y Acad Sci 1997, 826:493-497.
• [150]Jellinger KA, Attems J: Incidence of cerebrovascular lesions in Alzheimer’s disease: a postmortem study. Acta Neuropathol 2003, 105:14-17.
• [151]Knopman DS, Parisi JE, Boeve BF, Cha RH, Apaydin H, Salviati A, Edland SD, Rocca WA: Vascular dementia in a population-based autopsy study. Arch Neurol 2003, 60:569-575.
• [152]Fernando MS, Ince PG: Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004, 226:13-17.
• [153]Jellinger KA, Mitter-Ferstl E: The impact of cerebrovascular lesions in Alzheimer disease. A comparative autopsy study. J Neurol 2003, 250:1050-1055.
• [154]Brayne C, Richardson K, Matthews FE, Fleming J, Hunter S, Xuereb JH, Paykel E, Mukaetova-Ladinska EB, Huppert FA, O’Sullivan A, Dening T: Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge City over-75 s Cohort (CC75C) Study. J Alzheimers Dis 2009, 18:645-658.
• [155]Serrano-Pozo A, Qian J, Monsell SE, Frosch MP, Betensky RA, Hyman BT: Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the national Alzheimer coordinating center. J Neuropathol Exp Neurol 2013, 72:1182-1192.
• [156]Boyle PA, Wilson RS, Yu L, Barr AM, Honer WG, Schneider JA, Bennett DA: Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann Neurol 2013, 74:478-489.
• [157]Jellinger KA, Attems J: Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer’s disease. J Neurol Sci 2005, 229–230:37-41.
• [158]Jellinger KA: Pathology and pathogenesis of vascular cognitive impairment – a critical update. Front Aging Neurosci 2013, 5:17.
• [159]Kovacs GG, Milenkovic I, Wohrer A, Hoftberger R, Gelpi E, Haberler C, Honigschnabl S, Reiner-Concin A, Heinzl H, Jungwirth S, Krampla W, Fischer P, Budka H: Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol 2013, 126:365-384.
• [160]Carotenuto A, Rea R, Colucci L, Ziello AR, Molino I, Carpi S, Traini E, Amenta F, Fasanaro AM: Late and early onset dementia: what is the role of vascular factors? A retrospective study. J Neurol Sci 2012, 322:170-175.
• [161]White L, Small BJ, Petrovitch H, Ross GW, Masaki K, Abbott RD, Hardman J, Davis D, Nelson J, Markesbery W: Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia Aging Study. J Geriatr Psychiatry Neurol 2005, 18:224-227.
• [162]White L: Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia Aging Study. J Alzheimers Dis 2009, 18:713-725.
• [163]Corrada MM, Berlau DJ, Kawas CH: A population-based clinicopathological study in the oldest-old: the 90+ study. Curr Alzheimer Res 2012, 9:709-717.
• [164]Tsuang D, Simpson KL, Li G, Barnhart RL, Edland SD, Bowen J, McCormick W, Teri L, Nochlin D, Larson EB, Thompson ML, Leverenz JB: Evaluation of selection bias in an incident-based dementia autopsy case series. Alzheimer Dis Assoc Disord 2005, 19:67-73.
• [165]Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW, Johnson KA, Petersen LE, McDonald WC, Braak H, Petersen RC: Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 2003, 62:1087-1095.
• [166]Davis DG, Schmitt FA, Wekstein DR, Markesbery WR: Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 1999, 58:376-388.
• [167]Jentoft M, Parisi J, Dickson D, Johnson K, Boeve B, Knopman D, Petersen R: Neuropathologic findings in 32 nondemented elderly subjects (abs.). J Neuropathol Exp Neurol 2011, 70:531.
• [168]Buchman AS, Leurgans SE, Nag S, Bennett DA, Schneider JA: Cerebrovascular disease pathology and Parkinsonian signs in old age. Stroke 2011, 42:3183-3189.
• [169]Jellinger KA, Attems J: Neuropathology and general autopsy findings in nondemented aged subjects. Clin Neuropathol 2012, 31:87-98.
• [170]Wirth M, Villeneuve S, Haase CM, Madison CM, Oh H, Landau SM, Rabinovici GD, Jagust WJ: Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurol 2013, 70:1512-1519.
• [171]Roman GC, Kalaria RN: Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia. Neurobiol Aging 2006, 27:1769-1785.
• [172]Garde E, Lykke Mortensen E, Rostrup E, Paulson OB: Decline in intelligence is associated with progression in white matter hyperintensity volume. J Neurol Neurosurg Psychiatry 2005, 76:1289-1291.
• [173]Artero S, Tiemeier H, Prins ND, Sabatier R, Breteler MM, Ritchie K: Neuroanatomical localisation and clinical correlates of white matter lesions in the elderly. J Neurol Neurosurg Psychiatry 2004, 75:1304-1308.
• [174]Ihara M, Polvikoski TM, Hall R, Slade JY, Perry RH, Oakley AE, Englund E, O’Brien JT, Ince PG, Kalaria RN: Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies. Acta Neuropathol 2010, 119:579-589.
• [175]Tullberg M, Fletcher E, DeCarli C, Mungas D, Reed BR, Harvey DJ, Weiner MW, Chui HC, Jagust WJ: White matter lesions impair frontal lobe function regardless of their location. Neurology 2004, 63:246-253.
• [176]Malykhin N, Vahidy S, Michielse S, Coupland N, Camicioli R, Seres P, Carter R: Structural organization of the prefrontal white matter pathways in the adult and aging brain measured by diffusion tensor imaging. Brain Struct Funct 2011, 216:417-431.
• [177]Reed BR, Eberling JL, Mungas D, Weiner M, Kramer JH, Jagust WJ: Effects of white matter lesions and lacunes on cortical function. Arch Neurol 2004, 61:1545-1550.
• [178]Wen HM, Mok VC, Fan YH, Lam WW, Tang WK, Wong A, Huang RX, Wong KS: Effect of white matter changes on cognitive impairment in patients with lacunar infarcts. Stroke 2004, 35:1826-1830.
• [179]Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB: Functional network disruption in the degenerative dementias. Lancet Neurol 2011, 10:829-843.
• [180]De Vogelaere F, Santens P, Achten E, Boon P, Vingerhoets G: Altered default-mode network activation in mild cognitive impairment compared with healthy aging. Neuroradiology 2012, 54:1195-1206.
• [181]van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, Inzitari D, Erkinjuntti T, Crisby M, Waldemar G, Schmidt R, Fazekas F, Scheltens P: Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke 2005, 36:2116-2120.
• [182]van der Flier WM, van Straaten EC, Barkhof F, Ferro JM, Pantoni L, Basile AM, Inzitari D, Erkinjuntti T, Wahlund LO, Rostrup E, Schmidt R, Fazekas F, Scheltens P: Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. J Neurol Neurosurg Psychiatry 2005, 76:1497-1500.
• [183]Capizzano AA, Acion L, Bekinschtein T, Furman M, Gomila H, Martinez A, Mizrahi R, Starkstein SE: White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004, 75:822-827.
• [184]Schmidt R, Ropele S, Ferro J, Madureira S, Verdelho A, Petrovic K, Gouw A, van der Flier WM, Enzinger C, Pantoni L, Inzitari D, Erkinjuntti T, Scheltens P, Wahlund LO, Waldemar G, Rostrup E, Wallin A, Barkhof F, Fazekas F: Diffusion-weighted imaging and cognition in the leukoariosis and disability in the elderly study. Stroke 2010, 41:e402-e408.
• [185]Kövari E, Gold G, Herrmann FR, Canuto A, Hof PR, Michel JP, Bouras C, Giannakopoulos P: Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke 2004, 35:410-414.
• [186]Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T: Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 2004, 226:75-80.
• [187]Burhan AM, Bartha R, Bocti C, Borrie M, Laforce R, Rosa-Neto P, Soucy JP: Role of emerging neuroimaging modalities in patients with cognitive impairment: a review from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012. Alzheimers Res Ther 2013, 5:S4.
• [188]Kantarci K: Molecular imaging of Alzheimer disease pathology. AJNR Am J Neuroradiol 2014, 35:S12-S17.
• [189]Landau SM, Thomas BA, Thurfjell L, Schmidt M, Margolin R, Mintun M, Pontecorvo M, Baker SL, Jagust WJ: Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers. Eur J Nucl Med Mol Imaging 2014, 41:1398-1407.
• [190]Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R, Yates P, Piguet O, Pejoska S, Dore V, Yanai K, Masters CL, Kudo Y, Rowe CC, Okamura N: In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2014, 41:816-826.
• [191]Jack CR Jr, Barrio JR, Kepe V: Cerebral amyloid PET imaging in Alzheimer’s disease. Acta Neuropathol 2013, 126:643-657.
• [192]Kepe V, Moghbel MC, Langstrom B, Zaidi H, Vinters HV, Huang SC, Satyamurthy N, Doudet D, Mishani E, Cohen RM, Hoilund-Carlsen PF, Alavi A, Barrio JR: Amyloid-beta positron emission tomography imaging probes: a critical review. J Alzheimers Dis 2013, 36:613-631.
• [193]Mathis CA, Kuller LH, Klunk WE, Snitz BE, Price JC, Weissfeld LA, Rosario BL, Lopresti BJ, Saxton JA, Aizenstein HJ, McDade EM, Kamboh MI, DeKosky ST, Lopez OL: In vivo assessment of amyloid-beta deposition in nondemented very elderly subjects. Ann Neurol 2013, 73:751-761.
• [194]Roh JH, Lee JH: Recent updates on subcortical ischemic vascular dementia. J Stroke 2014, 16:18-26.
• [195]Kester MI, Goos JD, Teunissen CE, Benedictus MR, Bouwman FH, Wattjes MP, Barkhof F, Scheltens P, van der Flier WM: Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers. JAMA Neurol 2014, 71:855-862.