Challenges of multimorbidity of the aging brain: a critical update

Journal of Neural Transmission

Volumn 122, Issue 4, 2015, Pages 505-521

  Jellinger, Kurt A ^a   Attems, Johannes ^b  

^a INSTITUTE OF CLINICAL NEUROBIOLOGY   (Austria)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Alzheimer disease; Cerebral multimorbidity; Cerebrovascular lesions; Mixed pathology; Neurodegenerative disease; Proteinopathy

Indexed keywords

AGING; ANIMAL; BRAIN; BRAIN DISEASES; COMORBIDITY; HUMAN; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

AGING; ANIMALS; BRAIN; BRAIN DISEASES; COMORBIDITY; HUMANS;

EID: 84939892956     PISSN: 03009564     EISSN: 14351463     Source Type: Journal    
DOI: 10.1007/s00702-014-1288-x     Document Type: Review

References (209)

1. Aho L, Parkkinen L, Pirttila T, Alafuzoff I (2008) Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects. Dement Geriatr Cogn Disord 25:423–432
2. Alafuzoff I, Arzberger T, Al-Sarraj S, Bodi I, Bogdanovic N, Braak H, Bugiani O, Del-Tredici K, Ferrer I, Gelpi E, Giaccone G, Graeber MB, Ince P, Kamphorst W, King A, Korkolopoulou P, Kovacs GG, Larionov S, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Seilhean D, Tagliavini F, Stadelmann C, Streichenberger N, Thal DR, Wharton SB, Kretzschmar H (2008) Staging of neurofibrillary pathology in Alzheimer’s disease: a study of the BrainNet Europe Consortium. Brain Pathol 18:484–496
3. Alafuzoff I, Gelpi E, Al-Sarraj S, Arzberger T, Attems J, Bodi I, Bogdanovic N, Budka H, Bugiani O, Englund E, Ferrer I, Gentleman S, Giaccone G, Graeber M, Hortobagyi T, Höftberger R, Ironside JW, Jellinger KA, Kavantzas N, King A, Korkolopoulou P, Kovács GG, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Rozemuller A, Seilhean D, Streichenberger N, Thal DR, Wharton SB, Kretzschmar H (2012) The need to unify neuropathological assessments of vascular alterations in the ageing brain. Multicentre survey by the BrainNet Europe consortium. Exp Gerontol 47:825–833
4. Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, Graff-Radford NR, Hutton ML, Dickson DW (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445
5. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn (DSM-5). American Psychiatric Association Arlington, VA
6. Andin U, Gustafson L, Passant U, Brun A (2005) A clinico-pathological study of heart and brain lesions in vascular dementia. Dement Geriatr Cogn Disord 19:222–228
7. Arai T, Mackenzie IR, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, Iritani S, Onaya M, Akiyama H (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117:125–136
8. Arnold SE, Toledo JB, Appleby DH, Xie SX, Wang LS, Baek Y, Wolk DA, Lee EB, Miller BL, Lee VM, Trojanowski JQ (2013a) Comparative survey of the topographical distribution of signature molecular lesions in major neurodegenerative diseases. J Comp Neurol 521:4339–4355
9. Arnold SJ, Dugger BN, Beach TG (2013b) TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies. Acta Neuropathol 126:51–57
10. Arriagada PV, Marzloff K, Hyman BT (1992) Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer’s disease. Neurology 42:1681–1688
11. Asi YT, Ling H, Ahmed Z, Lees AJ, Revesz T, Holton JL (2014) Neuropathological features of multiple system atrophy with cognitive impairment. Mov Disord 29:884–888
12. Attems J (2005) Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms. Acta Neuropathol 110:345–359
13. Attems J, Jellinger K (2013a) Neuropathological correlates of cerebral multimorbidity. Curr Alzheimer Res 10:569–577
14. Attems J, Jellinger KA (2013b) Neuropathology. In: Dening T, Thomas A (eds) Oxford textbook of old age psychiatry, 2 edn. Oxford University Press, Oxford, pp 87–105
15. Attems J, Jellinger KA, Lintner F (2005) Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol 110:222–231
16. Attems J, Jellinger K, Thal DR, Van Nostrand W (2011) Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 37:75–93
17. Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS (2005) Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 64:834–841
18. Bennett DA, Schneider JA, Arvanitakis Z, Wilson RS (2012) Overview and findings from the religious orders study. Curr Alzheimer Res 9:628–645
19. Bigio EH, Mishra M, Hatanpaa KJ, White CL 3rd, Johnson N, Rademaker A, Weitner BB, Deng HX, Dubner SD, Weintraub S, Mesulam M (2010) TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease. Acta Neuropathol 120:43–54
20. Boyle PA, Wilson RS, Yu L, Barr AM, Honer WG, Schneider JA, Bennett DA (2013) Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann Neurol 74:478–489
21. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
22. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006a) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112:389–404
23. Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K (2006b) Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 21:2042–2051
24. Brayne C, Richardson K, Matthews FE, Fleming J, Hunter S, Xuereb JH, Paykel E, Mukaetova-Ladinska EB, Huppert FA, O’Sullivan A, Dening T (2009) Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study. J Alzheimers Dis 18:645–658
25. Bruns MB, Josephs KA (2013) Neuropsychiatry of corticobasal degeneration and progressive supranuclear palsy. Int Rev Psychiatry 25:197–209
26. Buchman AS, Leurgans SE, Nag S, Bennett DA, Schneider JA (2011) Cerebrovascular disease pathology and parkinsonian signs in old age. Stroke 42:3183–3189
27. Burns JM, Church JA, Johnson DK, Xiong C, Marcus D, Fotenos AF, Snyder AZ, Morris JC, Buckner RL (2005) White matter lesions are prevalent but differentially related with cognition in aging and early Alzheimer disease. Arch Neurol 62:1870–1876
28. Burrell JR, Hodges JR, Rowe JB (2014) Cognition in corticobasal syndrome and progressive supranuclear palsy: a review. Mov Disord 29:684–693
29. Byford M, Brayne C, McKeith I, Chatfield M, Ince P, Matthews F (2009) Lewy bodies and neuronal loss in subcortical areas and disability in non-demented older people: a population based neuropathological cohort study. BMC Geriatr 9:22
30. Cairns NJ, Taylor-Reinwald L, Morris JC (2010) Autopsy consent, brain collection, and standardized neuropathologic assessment of ADNI participants: the essential role of the neuropathology core. Alzheimers Dement 6:274–279
31. Cendes F, Sakamoto AC, Spreafico R, Bingaman W, Becker AJ (2014) Epilepsies associated with hippocampal sclerosis. Acta Neuropathol 128:21–37
32. Chertkow H, Feldman HH, Jacova C, Massoud F (2013) Definitions of dementia and predementia states in Alzheimer’s disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia. Alzheimers Res Ther 5:S2
33. Cholerton B, Larson EB, Baker LD, Craft S, Crane PK, Millard SP, Sonnen JA, Montine TJ (2013) Neuropathologic correlates of cognition in a population-based sample. J Alzheimers Dis 36:699–709
34. Chui HC (2006) Vascular cognitive impairment: today and tomorrow. Alzheimers Dement 2:185–194
35. Chui HC, Zarow C, Mack WJ, Ellis WG, Zheng L, Jagust WJ, Mungas D, Reed BR, Kramer JH, Decarli CC, Weiner MW, Vinters HV (2006) Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 60:677–687
36. Clinton LK, Blurton-Jones M, Myczek K, Trojanowski JQ, LaFerla FM (2010) Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci 30:7281–7289
37. Colom-Cadena M, Gelpi E, Charif S, Belbin O, Blesa R, Marti MJ, Clarimon J, Lleo A (2013) Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. J Neuropathol Exp Neurol 72:1203–1212
38. Compta Y, Parkkinen L, O’Sullivan SS, Vandrovcova J, Holton JL, Collins C, Lashley T, Kallis C, Williams DR, de Silva R, Lees AJ, Revesz T (2011) Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain 134:1493–1505
39. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Alafuzoff I, Arnold SE, Attems J, Beach TG, Cairns NJ, Dickson DW, Gearing M, Grinberg L, Hof PR, Hyman BT, Jellinger K, Kovacs GG, Knopman DS, Kofler J, Masliah E, McKee A, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White Iii CL, Wisniewski T, Woltjer RL, Yamada M, Nelson PT (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol (submitted)
40. Crystal H, Dickson D (2002) Cerebral infarcts in patients with autopsy proven Alzheimer’s disease (abstr.). Neurobiol Aging 23:207
41. Davidson YS, Raby S, Foulds PG, Robinson A, Thompson JC, Sikkink S, Yusuf I, Amin H, DuPlessis D, Troakes C, Al-Sarraj S, Sloan C, Esiri MM, Prasher VP, Allsop D, Neary D, Pickering-Brown SM, Snowden JS, Mann DM (2011) TDP-43 pathological changes in early onset familial and sporadic Alzheimer’s disease, late onset Alzheimer’s disease and Down’s syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathol 122:703–713
42. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58:376–388
43. Dawe RJ, Bennett DA, Schneider JA, Arfanakis K (2011) Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. PLoS One 6:e26286
44. de Calignon A, Polydoro M, Suarez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT (2012) Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron 73:685–697
45. DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, Frigerio R, Burnett M, Wszolek ZK, Uitti RJ, Ahlskog JE, Dickson DW (2008) Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol 65:1074–1080
46. Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, Kalaria RN (2012) Staging and natural history of cerebrovascular pathology in dementia. Neurology 78:1043–1050
47. Dickson DW, Davies P, Bevona C, Van Hoeven KH, Factor SM, Grober E, Aronson MK, Crystal HA (1994) Hippocampal sclerosis: a common pathological feature of dementia in very old (> or =80 years of age) humans. Acta Neuropathol 88:212–221
48. Dolan D, Troncoso J, Resnick SM, Crain BJ, Zonderman AB, O’Brien RJ (2010) Age, Alzheimer’s disease and dementia in the Baltimore longitudinal study of ageing. Brain 133:2225–2231
49. Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the Movement Disorder Society task force. Mov Disord 22:2314–2324
50. Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9:1118–1127
51. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert MO, Jicha GA, Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, Stern Y, Scheltens P, Cummings JL (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13:614–629
52. Dugger BN, Hentz JG, Adler CH, Sabbagh MN, Shill HA, Jacobson S, Caviness JN, Belden C, Driver-Dunckley E, Davis KJ, Sue LI, Beach TG (2014) Clinicopathological outcomes of prospectively followed normal elderly brain bank volunteers. J Neuropathol Exp Neurol 73:244–252
53. Duyckaerts C, Dickson DW (2011) Neuropathology of Alzheimer’s disease and its variants. In: Dickson DW, Weller RO (eds) Neurodegeneration. The molecular pathology of dementia and movement disorders, 2nd edn. Wiley-Blackwell, Oxford, pp 62–91
54. Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118:5–36
55. Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707
56. Erten-Lyons D, Dodge HH, Woltjer R, Silbert LC, Howieson DB, Kramer P, Kaye JA (2013a) Neuropathologic basis of age-associated brain atrophy. JAMA Neurol 70:616–622
57. Erten-Lyons D, Woltjer R, Kaye J, Mattek N, Dodge HH, Green S, Tran H, Howieson DB, Wild K, Silbert LC (2013b) Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology 81:977–983
58. Esiri MM (2010) Pro: can neuropathology really confirm the exact diagnosis? Alzheimers Res Ther 2:10
59. Esiri MM, Englund E (2014) Pathological aspects of the ischemic consequences of small vessel disease on brain parenchyma. In: Pantoni L, Gorelick PB (eds) Cerebral small vessel disease. Cambridge University Press, Cambridge, pp 16–28
60. Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD (1999) Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet 354:919–920
61. Esiri MM, Joachim C, Sloan C, Christie S, Agacinski G, Bridges LR, Wilcock GK, Smith AD (2014) 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 28:30–35
62. Fernando MS, Ince PG (2004) Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 226:13–17
63. Ferrer I (2010) Cognitive impairment of vascular origin: neuropathology of cognitive impairment of vascular origin. J Neurol Sci 299:139–149
64. Ferrer I, Santpere G, van Leeuwen FW (2008) Argyrophilic grain disease. Brain 131:1416–1432
65. Fischer P, Jungwirth S, Krampla W, Weissgram S, Kirchmeyr W, Schreiber W, Huber K, Rainer M, Bauer P, Tragl KH (2002) Vienna transdanube aging “VITA”: study design, recruitment strategies and level of participation. J Neural Transm Suppl 62:105–116
66. Frigerio R, Fujishiro H, Ahn TB, Josephs KA, Maraganore DM, Delledonne A, Parisi JE, Klos KJ, Boeve BF, Dickson DW, Ahlskog JE (2011) Incidental Lewy body disease: do some cases represent a preclinical stage of dementia with Lewy bodies? Neurobiol Aging 32:857–863
67. Fujimi K, Sasaki K, Noda K, Wakisaka Y, Tanizaki Y, Matsui Y, Sekita A, Iida M, Kiyohara Y, Kanba S, Iwaki T (2008) Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: the Hisayama study. Brain Pathol 18:317–325
68. Fujishima M, Kiyohara Y (2002) Incidence and risk factors of dementia in a defined elderly Japanese population: the Hisayama study. Ann NY Acad Sci 977:1–8
69. Gelber RP, Launer LJ, White LR (2012) The Honolulu-Asia aging study: epidemiologic and neuropathologic research on cognitive impairment. Curr Alzheimer Res 9:664–672
70. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640
71. Goedert M, Ghetti B, Spillantini MG (2012) Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb Perspect Med 2:a006254
72. Gold G, Kovari E, Herrmann FR, Canuto A, Hof PR, Michel JP, Bouras C, Giannakopoulos P (2005) Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia. Stroke 36:1184–1188
73. Gold G, Giannakopoulos P, Herrmann FR, Bouras C, Kovari E (2007) Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130:2830–2836
74. 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 (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/american stroke association. Stroke 42:2672–2713
75. Götz J, Götz NN (2009) Animal models for Alzheimer’s disease and frontotemporal dementia: a perspective. ASN Neuro 1:AN20090042
76. Grinberg LT, Heinsen H (2009) Argyrophilic grain disease: an update about a frequent cause of dementia. Dement Neuropsychol 3:2–7
77. Grinberg LT, Thal DR (2010) Vascular pathology in the aged human brain. Acta Neuropathol 119:277–290
78. Halliday GM, Bigio EH, Cairns NJ, Neumann M, Mackenzie IR, Mann DM (2012) Mechanisms of disease in frontotemporal lobar degeneration: gain of function versus loss of function effects. Acta Neuropathol 124:373–382
79. Horvath J, Herrmann FR, Burkhard PR, Bouras C, Kovari E (2013) Neuropathology of dementia in a large cohort of patients with Parkinson’s disease. Parkinsonism Relat Disord 19:864–868
80. Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097
81. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 8:1–13
82. Iadecola C (2010) The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 120:287–296
83. Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, Lee VM, Leverenz JB, Montine TJ, Duda JE, Hurtig HI, Trojanowski JQ (2012) Neuropathologic substrates of Parkinson disease dementia. Ann Neurol 72:587–598
84. Iseki E, Togo T, Suzuki K, Katsuse O, Marui W, de Silva R, Lees A, Yamamoto T, Kosaka K (2003) Dementia with Lewy bodies from the perspective of tauopathy. Acta Neuropathol (Berl) 105:265–270
85. Jack CR Jr (2012) Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology 263:344–361
86. Janocko NJ, Brodersen KA, Soto-Ortolaza AI, Ross OA, Liesinger AM, Duara R, Graff-Radford NR, Dickson DW, Murray ME (2012) Neuropathologically defined subtypes of Alzheimer’s disease differ significantly from neurofibrillary tangle-predominant dementia. Acta Neuropathol 124:681–692
87. Jellinger KA (2002) Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 109:813–836
88. Jellinger KA (2007a) The enigma of mixed dementia. Alzheimers Dement 3:40–53
89. Jellinger KA (2007b) More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains. Acta Neuropathol 114:299–303
90. Jellinger KA (2008) The pathology of “vascular dementia”: a critical update. J Alzheimers Dis 14:107–123
91. Jellinger KA (2010a) Con: can neuropathology really confirm the exact diagnosis? Alzheimers Res Ther 2:11
92. Jellinger KA (2010b) Prevalence and impact of cerebrovascular lesions in Alzheimer and Lewy body diseases. Neurodegener Dis 7:112–115
93. Jellinger KA (2012) Interaction between pathogenic proteins in neurodegenerative disorders. J Cell Mol Med 16:1166–1183
94. Jellinger KA (2013) Challenges in the neuropathological diagnosis of dementias. Int J Neuropathol 1:8–25
95. Jellinger KA (2014) Neuropathology of dementia disorders. J Alzheimers Dis Parkinsonism 4:1–17
96. Jellinger KA, Attems J (2005) Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer’s disease. J Neurol Sci 229–230:37–41
97. Jellinger KA, Attems J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113:107–117
98. Jellinger KA, Attems J (2008) Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol 115:427–436
99. Jellinger KA, Attems J (2010) Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis 21:1283–1298
100. Jellinger KA, Attems J (2012) Neuropathology and general autopsy findings in nondemented aged subjects. Clin Neuropathol 31:87–98
101. Jellinger KA, Attems J (2014) The overlap between vascular disease and Alzheimer’s––lessons from pathology. BMC Med (in press)
102. Jellinger KA, Mitter-Ferstl E (2003) The impact of cerebrovascular lesions in Alzheimer disease––a comparative autopsy study. J Neurol 250:1050–1055
103. Jentoft M, Parisi J, Dickson D, Johnson K, Boeve B, Knopman D, Petersen R (2011) Neuropathologic findings in 32 nondemented elderly subjects (abs.). J Neuropathol Exp Neurol 70:531
104. Jicha GA, Abner EL, Schmitt FA, Kryscio RJ, Riley KP, Cooper GE, Stiles N, Mendiondo MS, Smith CD, Van Eldik LJ, Nelson PT (2012) Preclinical AD workgroup staging: pathological correlates and potential challenges. Neurobiol Aging 33:622.e621–622.e616
105. Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M, Rademakers R, Boeve BF, Parisi JE, Smith GE, Ivnik RJ, Petersen RC, Jack CR Jr, Dickson DW (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857
106. Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM, Dickson DW (2011) Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 122:137–153
107. Josephs KA, Murray ME, Whitwell JL, Parisi JE, Petrucelli L, Jack CR, Petersen RC, Dickson DW (2014) Staging TDP-43 pathology in Alzheimer’s disease. Acta Neuropathol 127:441–450
108. Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T (2004) Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 226:75–80
109. Keage HA, Ince PG, Matthews FE, Wharton SB, McKeith IG, Brayne C (2012) Impact of less common and “disregarded” neurodegenerative pathologies on dementia burden in a population-based cohort. J Alzheimers Dis 28:485–493
110. 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 (2003) Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 62:1087–1095
111. Kotzbauer PT, Cairns NJ, Campbell MC, Willis AW, Racette BA, Tabbal SD, Perlmutter JS (2012) Pathologic accumulation of alpha-synuclein and A-beta in Parkinson disease patients with dementia. Arch Neurol 69:1326–1331
112. Kovacs GG, Alafuzoff I, Al-Sarraj S, Arzberger T, Bogdanovic N, Capellari S, Ferrer I, Gelpi E, Kovari V, Kretzschmar H, Nagy Z, Parchi P, Seilhean D, Soininen H, Troakes C, Budka H (2008) Mixed brain pathologies in dementia: the Brainnet Europe Consortium experience. Dement Geriatr Cogn Disord 26:343–350
113. Kovacs GG, Botond G, Budka H (2010) Protein coding of neurodegenerative dementias: the neuropathological basis of biomarker diagnostics. Acta Neuropathol 119:389–408
114. 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 (2013) Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol 126:365–384
115. Kovari E, Gold G, Herrmann FR, Canuto A, Hof PR, Michel JP, Bouras C, Giannakopoulos P (2004) Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke 35:410–414
116. Launer LJ, Petrovitch H, Ross GW, Markesbery W, White LR (2008) AD brain pathology: vascular origins? Results from the HAAS autopsy study. Neurobiol Aging 29:1587–1590
117. Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB (1999) Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 47:564–569
118. Liu Y, Yu JT, Sun FR, Ou JR, Qu SB, Tan L (2013) The clinical and pathological phenotypes of frontotemporal dementia with C9ORF72 mutations. J Neurol Sci 335:26–35
119. Lopez OL, McDade E, Riverol M, Becker JT (2011) Evolution of the diagnostic criteria for degenerative and cognitive disorders. Curr Opin Neurol 24:532–541
120. Love S, Chalmers K, Ince P, Esiri M, Attems J, Jellinger K, Yamada M, McCarron M, Minett T, Matthews F, Greenberg S, Mann D, Kehoe PG (2014) Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue. Am J Neurodegener Dis 3:19–32
121. Lu PH, Mendez MF, Lee GJ, Leow AD, Lee HW, Shapira J, Jimenez E, Boeve BB, Caselli RJ, Graff-Radford NR, Jack CR, Kramer JH, Miller BL, Bartzokis G, Thompson PM, Knopman DS (2013) Patterns of brain atrophy in clinical variants of frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 35:34–50
122. Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, Meinow B, Fratiglioni L (2011) Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 10:430–439
123. Markesbery WR, Jicha GA, Liu H, Schmitt FA (2009) Lewy body pathology in normal elderly subjects. J Neuropathol Exp Neurol 68:816–822
124. Matthews FE, Brayne C, Lowe J, McKeith I, Wharton SB, Ince P (2009) Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med 6:e1000180
125. McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872
126. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269
127. Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, Thal LJ, Corey-Bloom J (2003) Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 60:1586–1590
128. Miklossy J (2003) Cerebral hypoperfusion induces cortical watershed microinfarcts which may further aggravate cognitive decline in Alzheimer’s disease. Neurol Res 25:605–610
129. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486
130. Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol 123:1–11
131. Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW (2011) Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 10:785–796
132. Murray ME, Cannon A, Graff-Radford NR, Leisinger AM, Rutherford NJ, Ross OA, Duara R, Carrasquillo MM, Rademakers R, Dickson DW (2014) Differential clinicopathologic and genetic features of late-onset amnestic dementias. Acta Neuropathol. doi:10.1007/s00401-014-1302-2
133. Nagy Z, Esiri MM, Jobst KA, Morris JH, King E-F, McDonald B, Joachim C, Litchfield S, Barnetson L, Smith AD (1997) The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 56:165–170
134. Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR (2007) 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 66:1136–1146
135. Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Santacruz K, Smith CD, Patel E, Markesbery WR (2009) Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol 68:774–784
136. Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del Tredici K, Duyckaerts C, Frosch MP, Haroutunian V, Hof PR, Hulette CM, Hyman BT, Iwatsubo T, Jellinger KA, Jicha GA, Kovari E, Kukull WA, Leverenz JB, Love S, Mackenzie IR, Mann DM, Masliah E, McKee AC, Montine TJ, Morris JC, Schneider JA, Sonnen JA, Thal DR, Trojanowski JQ, Troncoso JC, Wisniewski T, Woltjer RL, Beach TG (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362–381
137. Nelson PT, Smith CD, Abner EL, Wilfred BJ, Wang WX, Neltner JH, Baker M, Fardo DW, Kryscio RJ, Scheff SW, Jicha GA, Jellinger KA, Van Eldik LJ, Schmitt FA (2013) Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease. Acta Neuropathol 126:161–177
138. Nolan KA, Lino MM, Seligmann AW, Blass JP (1998) Absence of vascular dementia in an autopsy series from a dementia clinic. J Am Geriatr Soc 46:597–604
139. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39:409–421
140. Oinas M, Polvikoski T, Sulkava R, Myllykangas L, Juva K, Notkola IL, Rastas S, Niinisto L, Kalimo H, Paetau A (2009) Neuropathologic findings of dementia with Lewy bodies (DLB) in a population-based Vantaa 85+ study. J Alzheimers Dis 18:677–689
141. Pantoni L, Sarti C, Alafuzoff I, Jellinger K, Munoz DG, Ogata J, Palumbo V (2006) Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services. Stroke 37:1005–1009
142. Parkkinen L, Pirttila T, Tervahauta M, Alafuzoff I (2005) Widespread and abundant alpha-synuclein pathology in a neurologically unimpaired subject. Neuropathology 25:304–314
143. Parkkinen L, Pirttila T, Alafuzoff I (2008) Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance. Acta Neuropathol 115:399–407
144. Perneczky R, Mosch D, Neumann M, Kretzschmar H, Muller U, Busch R, Forstl H, Kurz A (2005) The Alzheimer variant of Lewy body disease: a pathologically confirmed case–control study. Dement Geriatr Cogn Disord 20:89–94
145. Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, Braak H, Kokmen E (2006) Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 63:665–672
146. Petiet A, Delatour B, Dhenain M (2011) Models of neurodegenerative disease––Alzheimer’s anatomical and amyloid plaque imaging. Methods Mol Biol 771:293–308
147. Petrovitch H, Ross GW, Steinhorn SC, Abbott RD, Markesberry W, Davis DG, Nelson J, Hardman J, Masaki KH, Vogt MR, Launer LJ, White LR (2005) AD lesions and infarcts in demented and no-demented Japanese-American men. Ann Neurol 57:98–103
148. Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinisto L, Verkkoniemi A, Kainulainen K, Kontula K, Perez-Tur J, Hardy J, Haltia M (2001) Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Neurology 56:1690–1696
149. Polvikoski TM, van Straaten EC, Barkhof F, Sulkava R, Aronen HJ, Niinisto L, Oinas M, Scheltens P, Erkinjuntti T, Kalaria RN (2010) Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old. Neurology 75:2071–2078
150. Price JL, McKeel DW Jr, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, Smith CD, Davis DG, Schmitt FA, Markesbery WR, Kaye J, Kurlan R, Hulette C, Kurland BF, Higdon R, Kukull W, Morris JC (2009) Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging 30:1026–1036
151. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9:63–75
152. Purohit D, Batheja N, Haroutunian V, Sano M, Grossman H, Perl DP (2008) A clinicopathological correlation study of cognitive status and senile plaques and neurofibrillary tangles in clinically well-characterized individuals of extreme old age (abstract). J Neuropath Exp Neurol 67:494
153. Rahimi J, Kovacs GG (2014) Prevalence of mixed pathologies in the aging brain. Alzheimer Res Ther (in press)
154. Rauramaa T, Pikkarainen M, Englund E, Ince PG, Jellinger K, Paetau A, Alafuzoff I (2011) TAR-DNA binding protein-43 and alterations in the hippocampus. J Neural Transm 118:683–689
155. Rauramaa T, Pikkarainen M, Englund E, Ince PG, Jellinger K, Paetau A, Alafuzoff I (2013) Consensus recommendations on pathologic changes in the hippocampus: a postmortem multicenter inter-rater study. J Neuropathol Exp Neurol 72:452–461
156. Richardson K, Stephan BC, Ince PG, Brayne C, Matthews FE, Esiri MM (2012) The neuropathology of vascular disease in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Curr Alzheimer Res 9:687–696
157. Riley KP, Snowdon DA, Markesbery WR (2002) Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the nun study. Ann Neurol 51:567–577
158. Rincon F, Wright CB (2014) Current pathophysiological concepts in cerebral small vessel disease. Front Aging Neurosci 6:24
159. Robinson JL, Geser F, Corrada MM, Berlau DJ, Arnold SE, Lee VM, Kawas CH, Trojanowski JQ (2011) Neocortical and hippocampal amyloid-beta and tau measures associate with dementia in the oldest-old. Brain 134:3708–3715
160. Román GC (2008) The epidemiology of vascular dementia. In: Duyckaerts C, Litvan I (eds) Dementias––handbook of clinical neurology, vol 89 (3rd series). Elsevier, Edinburgh, pp 639–658
161. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop. Neurology 43:250–260
162. Sachdev P, Kalaria R, O’Brien J, Skoog I, Alladi S, Black SE, Blacker D, Blazer DG, Chen C, Chui H, Ganguli M, Jellinger K, Jeste DV, Pasquier F, Paulsen J, Prins N, Rockwood K, Roman G, Scheltens P (2014) Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord. doi:10.1097/WAD.0000000000000034
163. Santa-Maria I, Haggiagi A, Liu X, Wasserscheid J, Nelson PT, Dewar K, Clark LN, Crary JF (2012) The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol 124:693–704
164. Sarazin M, de Souza LC, Lehericy S, Dubois B (2012) Clinical and research diagnostic criteria for Alzheimer’s disease. Neuroimaging Clin N Am 22:23–32,viii
165. Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C (2009) Age, neuropathology, and dementia. N Engl J Med 360:2302–2309
166. 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 (2011) Heterogeneity in age-related white matter changes. Acta Neuropathol 122:171–185
167. Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR (2000) “Preclinical” AD revisited: neuropathology of cognitively normal older adults. Neurology 55:370–376
168. Schneider JA, Wilson RS, Cochran EJ, Bienias JL, Arnold SE, Evans DA, Bennett DA (2003) Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 60:1082–1088
169. Schneider JA, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 62:1148–1155
170. Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007a) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197–2204
171. Schneider JA, Boyle PA, Arvanitakis Z, Bienias JL, Bennett DA (2007b) Subcortical infarcts, Alzheimer’s disease pathology, and memory function in older persons. Ann Neurol 62:59–66
172. Schneider JA, Aggarwal NT, Barnes L, Boyle P, Bennett DA (2009) The neuropathology of older persons with and without dementia from community versus clinic cohorts. J Alzheimers Dis 18:691–701
173. Seltman RE, Matthews BR (2012) Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs 26:841–870
174. Serrano-Pozo A, Qian J, Monsell SE, Frosch MP, Betensky RA, Hyman BT (2013) Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the national Alzheimer coordinating center. J Neuropathol Exp Neurol 72:1182–1192
175. Shim YS, Roe CM, Buckles VD, Morris JC (2013) Clinicopathologic study of Alzheimer's disease: Alzheimer mimics. J Alzheimers Dis 35:799–811
176. Shim YS, Roe CM, Benzinger TL, Cairns NJ, Xiong C, Galvin JE, Coats MA, Yang D-W, Morris JC (2014) Pathological correlates of white matter hyperintensities on MRI. Dement Geriatric Cogn Disord (in press)
177. Sinka L, Kovari E, Gold G, Hof PR, Herrmann FR, Bouras C, Giannakopoulos P (2010) Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old. J Neuropathol Exp Neurol 69:1247–1255
178. Smallwood A, Oulhaj A, Joachim C, Christie S, Sloan C, Smith AD, Esiri M (2012) 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 38:337–343
179. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR (1997) Brain infarction and the clinical expression of Alzheimer disease. The nun study. JAMA 277:813–817
180. Sonnen JA, Santa Cruz K, Hemmy LS, Woltjer R, Leverenz JB, Montine KS, Jack CR, Kaye J, Lim K, Larson EB, White L, Montine TJ (2011) Ecology of the aging human brain. Arch Neurol 68:1049–1056
181. Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G, Gurvit H, Nacmias B, Pasquier F, Popescu BO, Rektorova I, Religa D, Rusina R, Rossor M, Schmidt R, Stefanova E, Warren JD, Scheltens P (2012) EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol 19:1159–1179
182. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292
183. Stankovic I, Krismer F, Jesic A, Antonini A, Benke T, Brown RG, Burn DJ, Holton JL, Kaufmann H, Kostic VS, Ling H, Meissner WG, Poewe W, Semnic M, Seppi K, Takeda A, Weintraub D, Wenning GK (2014) Cognitive impairment in multiple system atrophy: a position statement by the neuropsychology task force of the MDS multiple system atrophy (MODIMSA) study group. Mov Disord. doi:10.1002/mds.25880
184. Stephan BC, Matthews FE, Ma B, Muniz G, Hunter S, Davis D, McKeith IG, Foster G, Ince PG, Brayne C (2012) Alzheimer and vascular neuropathological changes associated with different cognitive states in a non-demented sample. J Alzheimers Dis 29:309–318
185. Strozyk D, Dickson DW, Lipton RB, Katz M, Derby CA, Lee S, Wang C, Verghese J (2010) Contribution of vascular pathology to the clinical expression of dementia. Neurobiol Aging 31:1710–1720
186. Tanskanen M, Makela M, Myllykangas L, Rastas S, Sulkava R, Paetau A (2012) Intracerebral hemorrhage in the oldest old: a population-based study (Vantaa 85+). Front Neurol 3:103
187. Thal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H (2002a) Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol 61:282–293
188. Thal DR, Rub U, Orantes M, Braak H (2002b) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800
189. Thal DR, Papassotiropoulos A, Saido TC, Griffin WS, Mrak RE, Kolsch H, Del Tredici K, Attems J, Ghebremedhin E (2010) Capillary cerebral amyloid angiopathy identifies a distinct APOE epsilon4-associated subtype of sporadic Alzheimer’s disease. Acta Neuropathol 120:169–183
190. Thal DR, Grinberg LT, Attems J (2012) Vascular dementia: different forms of vessel disorders contribute to the development of dementia in the elderly brain. Exp Gerontol 47:816–824
191. Thies W, Bleiler L (2013) Alzheimer’s disease facts and figures. Alzheimers Dement 9:208–245
192. Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136:2697–2706
193. Troncoso JC, Zonderman AB, Resnick SM, Crain B, Pletnikova O, O’Brien RJ (2008) Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann Neurol 64:168–176
194. Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697
195. Vanderstichele H, Bibl M, Engelborghs S, Le Bastard N, Lewczuk P, Molinuevo JL, Parnetti L, Perret-Liaudet A, Shaw LM, Teunissen C, Wouters D, Blennow K (2012) Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: a consensus paper from the Alzheimer’s Biomarkers Standardization Initiative. Alzheimers Dement 8:65–73
196. Wakisaka Y, Furuta A, Tanizaki Y, Kiyohara Y, Iida M, Iwaki T (2003) Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathol 106:374–382
197. Weiner MW, Aisen PS, Jack CR Jr, Jagust WJ, Trojanowski JQ, Shaw L, Saykin AJ, Morris JC, Cairns N, Beckett LA, Toga A, Green R, Walter S, Soares H, Snyder P, Siemers E, Potter W, Cole PE, Schmidt M (2010) The Alzheimer’s disease neuroimaging initiative: progress report and future plans. Alzheimers Dement 6(202–211):e207
198. White L (2009) 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 18:713–725
199. White L, Petrovitch H, Hardman J, Nelson J, Davis DG, Ross GW, Masaki K, Launer L, Markesbery WR (2002) Cerebrovascular pathology and dementia in autopsied Honolulu-Asia aging study participants. Ann NY Acad Sci 977:9–23
200. White L, Small BJ, Petrovitch H, Ross GW, Masaki K, Abbott RD, Hardman J, Davis D, Nelson J, Markesbery W (2005) Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia aging study. J Geriatr Psychiatry Neurol 18:224–227
201. Wills J, Jones J, Haggerty T, Duka V, Joyce JN, Sidhu A (2010) Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson’s disease brains with and without dementia. Exp Neurol 225:210–218
202. Wilson RS, Yu L, Trojanowski JQ, Chen EY, Boyle PA, Bennett DA, Schneider JA (2013) TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol 70:1418–1424
203. Wimo A, Jonsson L, Bond J, Prince M, Winblad B (2013) The worldwide economic impact of dementia 2010. Alzheimers Dement 9(1–11):e13
204. Wirth M, Villeneuve S, Haase CM, Madison CM, Oh H, Landau SM, Rabinovici GD, Jagust WJ (2013) Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people. JAMA Neurol 70:1512–1519
205. Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG (2008) Patterns and stages of alpha-synucleinopathy: relevance in a population-based cohort. Neurology 70:1042–1048
206. Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ (2002) Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol 103:481–487
207. Zekry D, Duyckaerts C, Belmin J, Geoffre C, Herrmann F, Moulias R, Hauw JJ (2003a) The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy. Neurobiol Aging 24:213–219
208. Zekry D, Duyckaerts C, Belmin J, Geoffre C, Moulias R, Hauw JJ (2003b) Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia. Acta Neuropathol 106:367–373
209. Zheng L, Vinters HV, Mack WJ, Zarow C, Ellis WG, Chui HC (2013) Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer pathologic changes. Stroke 44:2835–2841