Zerebrale Amyloidangiopathie – ein Update

M. Gahr; D. A. Nowak; B. J. Connemann; C. Schönfeldt-Lecuona

doi:10.1055/s-0032-1313218

Fortschritte der Neurologie · Psychiatrie, Inhaltsverzeichnis

Fortschr Neurol Psychiatr 2012; 80(11): 618-626
DOI: 10.1055/s-0032-1313218

Übersicht

Zerebrale Amyloidangiopathie – ein Update

Cerebral Amyloid Angiopathy – An Update

M. Gahr

¹Klinik für Psychiatrie und Psychotherapie III, Universitätsklinikum Ulm

,

D. A. Nowak

²Neurologische Fachklinik, Klinik Kipfenberg

,

B. J. Connemann

¹Klinik für Psychiatrie und Psychotherapie III, Universitätsklinikum Ulm

,

C. Schönfeldt-Lecuona

¹Klinik für Psychiatrie und Psychotherapie III, Universitätsklinikum Ulm

› Institutsangaben

Abstract

Zusammenfassung

Die zerebrale Amyloidangiopathie (ZAA), welche am häufigsten sporadisch, jedoch auch hereditär vorkommen kann, gehört zu den Amyloidosen und ist durch die Deposition und Akkumulation von beta-Amyloid (Aβ) in kleineren arteriellen Gefäßen des Gehirns charakterisiert. Die Ablagerung von Aβ führt zu degenerativen Veränderungen im zerebralen Gefäßsystem (Gefäßwandverdickungen, Mikroaneurysmen, Lumeneinengung, Dissektion), welche die Entwicklung der häufigsten ZAA-assoziierten klinischen Manifestationen (spontane intrazerebrale Blutungen) begünstigen. Neben Hämorrhagien können auch zerebrale Ischämien, transiente neurologische Symptome, Leukenzephalopathie sowie kognitive Einschränkungen bis hin zur Demenz im Zusammenhang mit der ZAA auftreten. Die sichere Diagnose einer ZAA kann nur auf der Grundlage einer pathologischen Beurteilung erfolgen, wenngleich Befunde der zerebralen Bildgebung und klinische Symptome eine wahrscheinliche ZAA diagnostizieren lassen. Kausale Therapieoptionen bestehen gegenwärtig nicht. Obwohl die ZAA in das Spektrum der neurologischen Erkrankungen verortet wird, können psychiatrische Symptome auftreten. In der Übersichtsarbeit werden neben epidemiologischen, pathogenetischen, klinischen und diagnostischen Aspekten mögliche psychiatrische Implikationen diskutiert.

Abstract

Cerebral amyloid angiopathy (CAA) belongs to the group of amyloidoses and is characterised by the deposition and accumulation of beta-amyloid (Aβ) in small arterial vessels of the brain. Hereditary forms of CAA exist but sporadic CAA is much more frequent. Deposition of Aβ induces degenerative changes of the cerebral vascular system (thickening of the vessel wall, constriction of vascular lumen, microaneurysms, dissection) that trigger the development of the typical clinical presentation of CAA, that is spontaneous intracerebral haemorrhage. Apart from haemorrhages, also cerebral ischaemia, transient neurological symptoms, leukencephalopathy as well as cognitive decline and dementia can occur in association with CAA. The definite diagnosis of CAA is only possible by means of pathological examination, even though neuroimaging and clinical findings allow the diagnosis of a probable CAA. Currently, no specific causal therapy exists. Although CAA is located in the range of neurological diseases psychiatric symptoms might occur. In the review, we discuss epidemiological, pathogenetic, clinical and diagnostic aspects and possible psychiatric implications of CAA.

Schlüsselwörter

Amyloidose - intrazerebrale Blutung - organische psychische Erkrankung - Schlaganfall - Wesensänderung

Key words

amyloidosis - intracerebral haemorrhage - mental disorder due to a medical condition - stroke - organic personality disorder

Volltext

Referenzen

Literatur
1 Biffi A, Greenberg S. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol 2011; 7: 1-9
2 Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med 2003; 349: 583-596
3 Perfetto F, Moggi-Pignone A, Livi R et al. Systemic amyloidosis: a challenge for the rheumatologist. Nat Rev Rheumatol 2010; 6: 417-429
4 Pezzini A, Del Zotto E, Volonghi I et al. Cerebral amyloid angiopathy: a common cause of cerebral hemorrhage. Curr Med Chem 2009; 16: 2498-2513
5 Viswanathan A, Greenberg S. Cerebral amyloid angiopathy in the elderly. Ann Neurol 2011; 70: 871-880
6 Lovelock C, Molyneux A, Rothwell P. Change of incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, betwen 1981 and 2006: a population-based study. Lancet Neurology 2007; 6: 487-493
7 Yoshimura M. Cerebral amyloid angiopathy: an overview. Neuropathology 2000; 1: 8-22
8 Block F. Zerebrale Amyoloidangiopathie. Nervenarzt 2011; 82: 202-206
9 Oppenheim G. Über „drusige Nekrosen“ in der Grosshirnrinde. Neurol Centralbl 1909; 28: 410-413
10 Divry P. Etude histochimique des plaques séniles. J Belge Neurol Psychiatry 1927; 27: 643-657
11 Scholz W. Die drusige Entartung der Hirnarterien und Capillaren. Gesamte Neurol Psychiatr 1938; 162: 694-715
12 Pantelakis S. A particular type of senile angiopathy of the central nervous system: congophilic angiopathy, topography and frequency. Monatsschr Psychiatr Neurol 1954; 128: 219-256
13 Okazaki H, Reagan T, Campbell R. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 1979; 54: 22-31
14 Glenner G, Wong C, Quaranta V et al. The amyloid deposits in Alzheimer’s disease: their nature and pathogenesis. Appl Pathol 1984; 2: 357-369
15 Glenner G, Wong C. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885-890
16 Yamada M, Naiki H. Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci 2012; 107: 41-78
17 Thanvi B, Robinson T. Sporadic cerebral amyloid angiopathy-an important cause of cerebral haemorrhage in older people. Age Ageing 2006; 35: 565-571
18 Zhang-Nunes S, Maat-Schieman M, van Duinen S et al. The cerebral amyloid angiopathies: hereditary and sporadic. Brain Pathol 2006; 16: 30-39
19 Revesz T, Holton J, Lashley T et al. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol 2009; 118: 115-130
20 Palsdottier A, Snorradottier A, Thorsteinsson L. Hereditary cystatin C amyloid angiopathy: genetic, clinical, and pathological aspects. Brain Pathol 2006; 16: 55-59
21 Reilly M, Staunton H. Peripheral nerve amyloidosis. Brain Pathol 1996; 6: 163-177
22 Ghiso J, Haltia M, Prelli F et al. Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type. Biochem J 1990; 272: 827-830
23 Ghetti B, Piccardo P, Spillantini M et al. Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A 1996; 93: 744-748
24 Greenberg S, Vonsattel J. Diagnosis of cerebral amyloid angiopathy. Sensitivity and specifity of cortical biopsy. Stroke 1997; 28: 1418-1422
25 Esiri M, Wilcock G. Cerebral amyloid angiopathy in dementia and old age. J Neurol Neurosurg Psychiat 1986; 49: 1221-1226
26 Keage H, Carare R, Friedland R et al. Populations based studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol 2009; 9: 3
27 Jellinger K. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 2002; 109: 813-836
28 Kalaria R, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999; 13 (Suppl. 03) 115-123
29 Ellis R, Olichney J, Thal L et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CREAD experience, Part XV. Neurology 1996; 46: 1592-1596
30 Pfeifer L, White L, Ross G et al. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 2002; 58: 1629-1634
31 Xuereb J, Brayne C, Dufouil C et al. Neuropathological findings in the very old. Results from the first 101 brains of a populations-based longitudinal study of dementing disorders. Ann N Y Acad Sci 2000; 903: 490-496
32 Neuropathology Group. Medical Research Council Cognitive function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet 2001; 357: 169-175
33 Tanskanen M, Lindsberg P, Tienari P et al. Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype. Neuropathol Appl Neurobiol 2005; 31: 589-599
34 Viswanathan A, Greenberg S. Chapter 38: Intracerebral hemorrhage. Handb Clin Neurol 2008; 93: 767-790
35 Vinters H. Cerebral amyloid angiopathy. Stroke 1987; 18: 311-324
36 Jellinger K. Cerebrovascular amyloidosis with cerebral hemorrhage. J Neurol 1977; 214: 195-206
37 Greenberg S. Stroke: Pathophysiology, Diagnosis and Management. New York: Harcourt Inc; 2004
38 Mastaglia F, Byrnes M, Johnson R et al. Prevalence of cerebral vascular amyloid-beta deposition and stroke in an aging Australian population: a postmortem study. J Clin Neurosci 2003; 10: 186-189
39 Campbell D, Bruins S, Vogel H et al. Intracerebral hemorrhage caused by cerebral amyloid angiopathy in a 53-year old man. J Neurol 2008; 9: 597-598
40 Lloyd-Jones D, Evans J, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA 2005; 294: 466-472
41 Vonsattel J, Myers R, Hedley-Whyte E et al. Cerebral amyloid angiopathy without and with cerebral hemorrhage: a comparative histological study. Ann Neurol 1991; 30: 637-649
42 Arima H, Tzourio C, Anderson C et al. Effects of peridopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke 2010; 41: 394-396
43 Ferreiro J, Ansbacher L, Vinters H. Stroke related to cerebral amyloid angiopathy: the significance of systemic vascular disease. J Neurol 1989; 236: 267-272
44 Broderick J, Brott T, Tomsick T et al. Lobar hemorrhage in the elderly. The undiminishing importance of hypertension. Stroke 1993; 24: 49-51
45 Masuda J, Tanaka K, Ueda K et al. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. Stroke 1988; 19: 205-210
46 Verghese P, Castellano J, Holtzmann D. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurology 2011; 10: 241-252
47 Mahley R, Rall SJ. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000; 1: 507-537
48 Holtzman D. Role of apoe/Abeta interactions in the pathogenesis of Alzheimer’s disease and cerebral amyloid angiopathy. J Mol Neurosci 2001; 17: 147-155
49 Premkumar D, Cohen D, Hedera P et al. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol 1996; 148: 2083-2095
50 Greenberg S, Rebeck G, Vonsattel J et al. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38: 254-259
51 Biffi A, Sonni A, Anderson C et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 2010; 68: 934-943
52 Nicoll J, Burnett C, Love S et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997; 41: 716-721
53 Greenberg S, Vonsattel J, Segal A et al. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998; 50: 961-965
54 McCarron M, Nicoll J, Stewart J et al. The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol 1999; 58: 711-718
55 Greenberg S, Briggs M, Hyman B et al. Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke 1996; 27: 1333-1337
56 Biffi A, Sonni A, Anderson C et al. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet Neurology 2011; 10: 702-709
57 Montaner J. Genetics of intracerebral haemorrhage: a tsunami effect of APOE ε2 genotype on brain bleeding size?. Lancet Neurology 2011; 10: 673-675
58 O’Donnell H, Rosand J, Knudsen K et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000; 342: 240-245
59 Schmechel D, Saunders A, Strittmatter W et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90: 9649-9653
60 Yamada M, Sodeyama N, Itoh Y et al. Association of presenilin-1 polymorphism with cerebral amyloid angiopathy in the elderly. Stroke 1997; 28: 2219-2221
61 Durany N, Ravid R, Riederer P et al. Increased frequency of the alpha-1-antichymotrypsin T allele in cerebral amyloid angiopathy. Neuropathology 2000; 20: 184-189
62 Yamada M, Sodeyama N, Itoh Y et al. Association of aloha1-antichymotrypsin polymorphism with cerebral amyloid angiopathy. Ann Neurol 1998; 44: 129-131
63 Yamada M, Sodeyama N, Itoh Y et al. Association of neprilysin polymorphism with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiat 2003; 74: 749-751
64 Shi J, Tian J, Pritchard A et al. A 3‘-UTR polymorphism in the oxidised LDL-receptor 1 gene increases Abeta40 load as cerebral amyloid angiopathy in Alzheimer’s disease. Acta Neuropathol 2006; 111: 15-20
65 Cristoforidis M, Schober R, Krohn K. Genetic-morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2005; 31: 11-19
66 Chapuis J, Hot D, Hansmannel F et al. Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer’s disease. Mol Psychiatry 2009; 14: 1004-1016
67 Hamaguchi T, Okino S, Sodeyama N et al. Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 2005; 76: 696-699
68 Revesz T, Ghiso J, Lashley T et al. Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 2003; 62: 885-898
69 Attems J, Jellinger K, Thal J et al. Review: Sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2011; 37: 75-93
70 Robakis N, Ramakrishna N, Wolfe G et al. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci U S A 1987; 84: 4190-4194
71 Goldgraber D, Lerman M, McBride O et al. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 1987; 235: 877-880
72 Haass C, Schlossmacher M, Hung A et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 1992; 359: 322-325
73 Busciglio J, Gabuzda D, Matsudaira P et al. Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc Natl Acad Sci U S A 1993; 90: 2092-2096
74 Harper J, Lieber C, Lansbury PJ. Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer’s disease amyloid beta-protein. Chem Biol 1997; 4: 951-959
75 Ishii K, Tamaoka A, Mizusawa H et al. Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer’s disease. Brain Res 1997; 748: 250-252
76 Rostagno A, Lal R, Ghiso J. Protein misfolding, aggregation, and fibril formation: common features of cerebral and non-cerebral amyloid diseases. In: Dawbarn D, Allen S, (eds) The neurobiology of Alzheimer’s disease.. Oxford: Oxford University Press; 2007: 133-160
77 Smith E, Greenberg S. Beta-amyloid, blood vessels, and brain function. Stroke 2009; 40: 2601-2606
78 Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurology 2010; 255: 597-598
79 Dotti C, De Strooper B. Alzheimer’s dementia by circulation disorders: when trees hide th forest. Nat Cell Biol 2009; 11: 114-116
80 Olichney J, Hansen L, Hofstetter C et al. Cerebral infarction in Alzheimer’s disease is associated with severe amyloid angiopathy and hypertension. Arch Neurol 1995; 52: 702-708
81 Mandybur T. Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol 1986; 45: 79-90
82 Zekry D, Duyckaerts C, Belmin J et al. Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia. Acta Neuropathol 2003; 106: 367-373
83 Shin H, Jones P, Garcia-Alloza M et al. Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy. Brain 2007; 130: 2310-2319
84 Cadavid D, Mena H, Koeller K et al. Cerebral beta amyloid angiopathy is a risk factor for cerebral ischemic infarction. A case control study in human brain biopsies. J Neuropathol Exp Neurol 2000; 59: 768-773
85 Zhang F, Eckman C, Younkin S et al. Increased susceptibility to ischemic brain damage in trangenic mice overexpressing the amyloid precursor protein. J Neurosci 1997; 17: 7655-7661
86 Wisniewski H, Wegiel J. Beta-amyloid formation by myocytes of leptomeningeal vessels. Acta Neuropathol 1994; 87: 233-241
87 Kawarabayashi T, Shoji M, Sato M et al. Accumulation of beta-amyloid fibrills in pancreas of transgenic mice. Neurobiol Aging 1996; 17: 215-222
88 Calhoun M, Burgermeister P, Phinney A et al. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci U S A 1999; 96: 14088-14093
89 Herzig M, van Nostrand W, Jucker M. Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models. Brain Pathol 2006; 16: 40-54
90 Love S, Miners S, Palmer J et al. Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Front Biosci 2009; 14: 4778-4792
91 Burgermeister P, Calhoun M, Winkler D et al. Mechanisms of cerebrovascular amyloid deposition. Lessons from mouse models. Ann N Y Acad Sci 2000; 903: 307-316
92 Fryer J, Simmons K, Parsadanian M et al. Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic mouse model. J Neurosci 2005; 25: 2803-2810
93 Bu G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 2009; 10: 333-344
94 Preston S, Steart P, Wilkinson A et al. Capillary and arterial amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol 2003; 29: 106-117
95 Weller R, Nicoll J. Cerebral amyloid angiopathy: both viper and maggot in the brain. Ann Neurol 2005; 58: 348-350
96 Weller R, Djuanda E, Yow H et al. Lymphatic drainage of the brain and the pathophysiology of neurological diseases. Acta Neuropathol 2009; 117: 1-14
97 Schley D, Carare-Nnadi R, Please C et al. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 2006; 238: 962-974
98 Vinters H, Gilbert J. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke 1983; 14: 924-928
99 Attems J, Jellinger K, Lintner F. Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol (Berlin) 2005; 110: 222-231
100 Yamada M, Tsukagoshi H, Otomo E et al. Cerebral amyloid angiopathy in the aged. J Neurol 1987; 234: 371-376
101 Attems J. Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms. Acta Neuropathol 2005; 110: 345-359
102 Thal J, Ghebremedhin E, Orantes M et al. Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 2003; 62: 1287-1301
103 Charidimou A, Gang Q, Werring D. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiat 2012; 83: 124-137
104 Greenberg S, Vonsattel J, Stakes J et al. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 1993; 43: 2073-2079
105 Knudson K, Rosand J, Karluk D et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston citeria. Neurology 2001; 56: 537-539
106 Attems J, Lauda F, Jellinger K. Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. J Neurol 2008; 255: 70-76
107 Jellinger K, Lauda F, Attems J. Sporadic cerebral amyloid angiopathy is not a frequent cause of spontaneous brain hemorrhage. Eur J Neurol 2007; 14: 923-928
108 Ritter M, Droste D, Hegedus K et al. Role of cerebral amyloid angiopathy in intracerebral hemorrhage in hypertensive patients. Neurology 2005; 64: 1233-1237
109 Olichney J, Hansen L, Hofstetter C et al. Association between severe cerebral amyloid angiopathy and cerebrovascular lesions in Alzheimer disease is not a spurious one attributable to apolipoprotein E4. Arch Neurol 2000; 57: 869-874
110 Greenberg S, Eng J, Ning M et al. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004; 35: 1415-1420
111 Greenberg S, Vernooij M, Cordonnier C et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurology 2009; 8: 165-174
112 Greenberg S, Nandigam R, Delgado P et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke 2009; 40: 2382-2386
113 Rosand J, Muzikansky A, Kumar A et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol 2005; 58: 459-462
114 Grinberg L, Thal D. Vascular pathology in the aged human brain. Acta Neuropathol 2010; 119: 277-290
115 Soontornniyomkij V, Lynch M, Mermash S et al. Cerebral microinfarction associated with severe cerebral beta-amyloid angiopathy. Brain Pathol 2010; 20: 459-467
116 Haglund M, Passant U, Sjöbeck M et al. Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia. Int J Geriatr Psychiatry 2006; 21: 681-687
117 Suter O, Sunthorn T, Kraftsik R et al. Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease. Stroke 2002; 33: 1986-1992
118 Okamoto Y, Ihara M, Fujita Y et al. Cortical microinfarcts in Alzheimer’s disease and subcortical vascular dementia. Neuroreport 2009; 20: 990-996
119 Levy M, Turtzo C, Llinas R. Superficial siderosis: a case report and review of the literature. Nat Clin Pract Neurol 2007; 3: 54-58 ; quiz 59
120 Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346-1350
121 Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol 2007; 64: 491-496
122 Fearnley J, Stevens J, Rudge P. Superficial siderosis of the central nervous system. Brain 1995; 118 (04) 1051-1066
123 Roch J, Nighoghossian N, Hermier M et al. Transient Neurologic Symptoms Related to Cerebral Amyloid Angiopathy: Usefulness of T2*-Weighted Imaging. Cerebrovasc Dis 2005; 20: 412-414
124 Smith E. Leukoaraiosis and stroke. Stroke 2010; 41: 139-143
125 Holland C, Smith E, Csapo I et al. Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke 2008; 39: 1127-1133
126 Scolding N, Joseph F, Kirby P et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 2005; 128 (03) 500-515
127 Oh U, Gupta R, Krakauer J et al. Reversible leukoencephalopathy associated with cerebral amyloid angiopathy. Neurology 2004; 62: 494-497
128 Eng J, Frosch M, Choi K et al. Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol 2004; 55: 494-497
129 Kinnecom C, Lev M, Wendell L et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68: 1411-1416
130 Chung K, Anderson N, Hutchinson D et al. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry 2011; 82: 20-26
131 Cano L, Martinez-Yelamos S, Majos C et al. Reversible leukoencephalopathy as a form of presentation in cerebral amyloid angiopathy. J Neurol Sci 2010; 288: 190-193
132 Greenberg S, Gurol M, Rosand J et al. Amyloid angiopathy-related vascular cognitive impairment. Stroke 2004; 35 (11) 2616-2619
133 Gorelick P, Scuteri A, Black S et al. 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
134 Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales (MRC CFAS). Lancet 2001; 357: 169-175
135 Arvanitakis Z, Leurgans S, Wang Z et al. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011; 69: 320-327
136 Berlit P, Gross W, Herrlinger U et al. Zerebrale Vaskulitis. In: AWMF (ed) Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Georg Thieme Verlag; 2008: 654 ff
137 van Rooden S, van der Grond J, van den Boom R et al. Descriptive analysis of the Boston criteria applied to a Dutch-type cerebral amyloid angiopathy population. Stroke 2009; 40: 3022-3027
138 Ayaz M, Boikov A, Haacke E et al. Imaging cerebral microbleeds using susceptibility weighted imaging: one step toward detecting vascular dementia. J Magn Reson Imaging 2010; 31: 142-148
139 Vernooij M, van der Lugt A, Ikram M et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008; 70: 1208-1214
140 Greenberg S, Grabowski T, Gurol M et al. Detection of isolated cerebrovascular beta-amyloid with Pittsburgh compound B. Ann Neurol 2008; 64: 587-591
141 Johnson K, Gregas M, Becker J et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 2007; 62: 229-234
142 de Jong D, Kremer B, Olde Rikkert M et al. Current state and future directions of neurochemical biomarkers for Alzheimer’s disease. Clin Chem Lab Med 2007; 45: 1421-1434
143 Verbeek M, Kremer B, Rikkert M et al. Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009; 66: 245-249
144 Lee A, Rudkin A, Agzarian M et al. Retinal vascular abnormalities in patients with cerebral amyloid angiopathy. Cerebrovasc Dis 2009; 28: 618-622
145 Greene G, Godersky J, Biller J et al. Surgical experience with cerebral amyloid angiopathy. Stroke 1990; 21: 1545-1549
146 Leblanc R, Preul M, Robitaille Y et al. Surgical considerations in cerebral amyloid angiopathy. Neurosurgery 1991; 29: 712-718
147 Izumihara A, Ishihara T, Iwamoto N et al. Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Stroke 1999; 30: 29-33
148 Eckman M, Wong L, Soo Y et al. Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help?. Stroke 2008; 39: 3308-3315
149 Vernooij M, Haag M, van der Lugt A et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol 2009; 66: 714-720
150 Wong K, Mok V, Lam W et al. Aspirin-associated intracerebral hemorrhage: clinical and radiologic features. Neurology 2000; 54: 2298-2301
151 Gervais F, Paquette J, Morissette C et al. Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 2007; 28: 537-547
152 Greenberg S, Rosand J, Schneider A et al. A phase 2 study of tramiprosate for cerebral amyloid angiopathy. Alzheimer Dis Assoc Disord 2006; 20: 269-274
153 James B, Bennett D, Boyle P et al. Dementia from Alzheimer disease and mixed pathologies in the oldest old. JAMA 2012; 307: 1798-1800
154 Robins Wahlin T, Byrne G. Personality changes in Alzheimer’s disease: a systematic review. Int J Geriatr Psychiatry 2011; 26: 1019-1029
155 Castellani J, Rolston R, Smith M. Alzheimer Disease. Dis Mon 2010; 56: 484-546