Current Neurology and Neuroscience Reports
https://doi.org/10.1007/s11910-019-0981-4

(2019) 19:64

BEHAVIOR (H. KIRSHNER, SECTION EDITOR)

Atypical Clinical Manifestations of Cerebral Amyloid Angiopathy
Carolyn Akers 1 & Lealani May Y. Acosta 1 & Ciaran Considine 1 & Daniel Claassen 1 & Howard Kirshner 1 & Matthew Schrag 1

# Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract
Purpose Cerebral amyloid angiopathy is a vasculopathy caused by β-amyloid deposition in cerebral arterioles and capillaries. It
is closely linked to Alzheimer’s disease and predisposes elderly patients to intracerebral hemorrhage, transient focal neurological
episodes, and cognitive impairment. Because of a predilection for symptomatic hemorrhage, particularly in the frontal lobes,
cerebral amyloid angiopathy may also cause a dysexecutive syndrome.
Recent Findings In this case series, we describe presentations of classic clinical dementia syndromes which are not are widely
thought to be associated with cerebral amyloid angiopathy, namely logopenic variant primary progressive aphasia (n = 3), normal
pressure hydrocephalus (n = 3), and Lewy body dementia (n = 2). In every case, after a clinical diagnosis was established,
neuroimaging, brain biopsy, and/or autopsy confirmed the presence of cerebral amyloid angiopathy.
Summary Cerebral amyloid angiopathy has significant clinical implications, and its ability to mimic and/or contribute to other
clinical dementia syndromes can complicate its diagnosis. This series of cases broadens the range of clinical scenarios associated
with cerebral amyloid angiopathy.
Keywords Cerebral amyloid angiopathy . Alzheimer’s disease . Aphasia . Hydrocephalus . Lewy body . Hallucinations

Introduction
Cerebral amyloid angiopathy (CAA) is a small vessel disease of
the brain in which the β-amyloid peptide forms rigid, ringshaped deposits in arterioles, and less commonly in capillaries
and small veins in the gray matter of the brain [1]. This is associated with complement activation; connective tissue remodeling; dysfunction and eventual loss of vascular smooth muscle,
which leads to altered autoregulation; and ultimately vascular
degeneration [2]. While classically associated with hemorrhage,
this process also leads to microischemic injury [3, 4]. Cerebral
microhemorrhages in a typical pattern are a reliable biomarker
for CAA. Iron sensitive MRI sequences (gradient echo T2* and
susceptibility weighted imaging) are used to identify microangiopathic changes [5–7]. CAA is classically associated with
Alzheimer’s disease (AD), intracerebral hemorrhage in the

This article is part of the Topical Collection on Behavior
* Matthew Schrag
matthew.schrag@vanderbilt.edu
1

Department of Neurology, Vanderbilt University Medical Center,
Medical Research Building III, 465 21st Avenue S, Suite 6160
(Office 6158C), Nashville, TN 37240, USA

elderly, and transient focal neurological episodes (TFNEs or colloquially, “amyloid spells”) [8–10]. Of AD cases, 75–90% also
demonstrate some degree of CAA, suggesting that CAA may
have a pathogenic role in the progression of cognitive decline in
AD [11, 12]. Furthermore, CAA has been shown to contribute
independently to cognitive impairment and interact with parenchymal AD pathology [13]. Consistent with the cortical production of β-amyloid, hemorrhages related to CAA are generally
lobar [14]. While patient outcomes are often better than their
counterparts with intracerebral hemorrhage related to hypertension, there is a high re-hemorrhage rate [15].
TFNEs are associated with cortical superficial siderosis
(cSS). A recent study of patients with cSS found that 24.6%
of patients with cSS also had a history of TFNEs, as opposed
to only 8.1% of patients without cSS [16]. cSS has also been
shown to be closely associated with CAA, although trauma,
reversible cerebral vasoconstriction syndrome and septic
embolism from infective endocarditis can mimic these
findings [17, 18]. Because of the association between CAA
and TNFEs, patients with TFNEs may be at a higher risk of
subsequent hemorrhage. While not entirely understood, the
mechanism of TFNEs is likely epileptiform.
Understanding the full breadth of the clinical spectrum of
CAA is important to identify and treat appropriate patients.
Moreover, it is becoming increasingly recognized that

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multiple neurodegenerative pathologies often coexist and interact, and the presence of CAA in the context of other neurodegenerative pathologies may be an important variable. In
this paper, we present a series of patients with classical clinical
dementia syndromes which are not typically thought to be
associated with CAA—logopenic variant primary progressive
aphasia (n = 3), normal pressure hydrocephalus (n = 3), and
Lewy body dementia (n = 2).

Cases
All cases were encountered in the course of clinical care in the
Vanderbilt University Medical Center, Department of
Neurology. This study was authorized by the Institutional
Review Board, IRB # 180287, Observational Study of
Cerebral Amyloid Angiopathy and Related disorders
(OSCAAR).

Primary Progressive Aphasia
Our first patient presented at age 76 after 2 to 3 years of
progressive difficulty with her speech. She had notable deficits in naming and repetition with mild reductions in fluency.
When asked to repeat “No ifs, ands or buts,” she would say
“No ins, bits, buts.” Formal neuropsychological testing confirmed a clinical syndrome typical of logopenic variant
primary progressive aphasia. Neuroimaging is shown in
Fig. 1a, b and demonstrated scattered white matter changes,
focal microhemorrhages in the left temporal and parietal
lobes, and asymmetric atrophy, particularly in the left parietal
and occipital lobes with accompanying ex vacuo changes in
the left occipital horn of the lateral ventricle. Importantly, the
focality of the findings observed on MRI aligns with the expected localization of her clinical symptoms. These highly
focal cerebral microhemorrhages may suggest focally severe
vasculopathy—this type of focality has occasionally been reported in pathological series of patients with CAA [19]. It may
also be due to an unrecognized episode of CAA-related inflammation (CAARI), in which vasculitis results from an autoimmune reaction to vascular β-amyloid deposits [20]. This
often causes focally severe microhemorrhagic changes with
transient cerebral edema, and emerging literature suggests that
some patients may be nearly asymptomatic [21, 22]. A remote
episode of CAARI would look similar to the imaging findings
depicted. Her symptoms have worsened at a moderate pace
over the 2 years following her diagnosis, and she has developed intermittent paranoia, hallucinations, and depression
along with worsening of her language and memory deficits.
At current follow-up, she is without symptomatic hemorrhage.
Two additional cases were identified that met clinical
criteria for primary progressive aphasia and had neuroimaging

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features of CAA. One had the onset of subjective cognitive
symptoms, primarily short-term memory impairment and
trouble multitasking, at age 62. At the same time, she noted
episodes of left facial numbness lasting 45 min and occurring
every few months. Neuropsychological testing revealed difficulty with verbal list learning (CVLT-II) more than with visual
memory (CVMT). Follow-up testing 15 months later revealed
progressive difficulty with naming, and 3 years from the initial
presentation her naming and fluency were substantially impaired. At this evaluation, she had slowed processing speed,
the emergence of symptoms of executive dysfunction, and she
had begun to require assistance with activities of daily living.
Brain MRI showed focal atrophy in the dominant parietal
lobe, with white matter hyperintensities and scattered
microhemorrhages in a pattern consistent with CAA. Her
symptoms have continued to progress, and at age 73 she required assistance with most activities of daily living.
Our final patient with primary progressive aphasia was a
retired schoolteacher, who presented at age 67 with 2 years of
“trouble finishing sentences,” along with short-term memory
loss. She noted that the severity of symptoms fluctuated considerably from day-to-day. Initial examinations noted impaired repetition, broken prosody, and decreased short-term
recall (recalled one of three items at 5 min). Brain MRI
showed extensive white matter disease and asymmetric prominence of the occipital horn of the left lateral ventricle (no
GRE-T2* or susceptibility weighted imaging was obtained
at this time). Two years later, after mild progression of her
symptoms, she presented to the emergency department with
the worst headache of her life. She was found to have a cortical subarachnoid hemorrhage overlying the left frontal lobe
near the Broca’s area. Repeat MRI at this time demonstrated
scattered microhemorrhages consistent with CAA (Fig. 1c).
Two months after her subarachnoid hemorrhage, she suffered
an intraparenchymal hemorrhage in the left anterior temporal
lobe. Her language and other cognitive symptoms continued
to progress, and she died 15 months later.

Normal Pressure Hydrocephalus
We present three patients with a clinical syndrome and neuroimaging consistent with hydrocephalus, documented normal
intracranial pressure, and MRI evidence of CAA. Two had
remarkable improvement with ventriculoperitoneal shunting,
while one elected not to undertake a surgical intervention.
Our first case was an 86-year-old gentleman with chronic
gait imbalance and several falls. Several years prior, he tested
within normal ranges on neuropsychological measures, but he
had subjective memory impairment which he felt was worsening, as well as falling for a financial scam. He had difficulty
lifting his feet and had episodes of leg freezing and gait hesitation requiring him to walk with a cane. A CT myelogram

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Fig. 1 Primary progressive aphasia and cerebral amyloid angiopathy. a
FLAIR and b GRE-T2* sequences from a patient who clinically had the
logopenic variant of primary progressive aphasia. She has scattered white
matter hyperintensity and focal atrophy of the left parieto-occipital area
accompanied by ex vacuo expansion of the occipital horn of the left lateral
ventricle. She had one cerebral microhemorrhage in the right frontal lobe,
but the majority of microhemorrhages clustered in the left

temporoparietal area. c GRE-T2* and FLAIR images from another
patient with primary progressive aphasia showing acute subarachnoid
bleeding (arrowheads) near the Broca’s area occurring several years
after the onset of aphasia. She also has scattered microhemorrhage
(arrows) and white matter changes. d The same patient 2 months later
suffered an intracerebral hemorrhage of the left anterior temporal lobe

showed an L3–4 lumbar stenosis, which was not felt to be
severe enough to account for his symptoms. MRI of the brain
(Fig. 2a) demonstrated enlarged ventricles characteristic of
normal pressure hydrocephalus, and he had improvement of
his symptoms with a large volume lumbar puncture. He
underwent ventriculoperitoneal shunting at age 86 with a resolution of the hydrocephalus and a substantial improvement in
his mobility. Brain biopsy obtained at the time of shunt placement demonstrated CAA without neuritic plaques or neurofibrillary tangles. A CT scan performed at age 90 captured two
small acute microhemorrhages and decompression of the ventricular system (Fig. 2b). The clinical improvement after
shunting was durable for several years, though his cognitive
deficits eventually progressed, and he died of pneumonia
while in hospice care at age 91. His family donated his brain
for study; innumerable cerebral microhemorrhages were
grossly observed and tissue staining revealed severe CAA
with minimal plaques or tangles (Fig. 2c, d).
Our second patient presented at age 84 with worsening
short-term memory for over 10 years. He had severe white
matter disease and hundreds of cerebral microhemorrhages
in a pattern we thought suggestive of mixed hypertensive

disease and CAA. He had been incontinent of urine for several
years and had a 1-year history of impairment of gait with
retropulsion and parkinsonism. This latter symptom rendered
him essentially wheelchair-bound, and he required continuous
care. His mobility improved minimally with dopaminergic
therapy. He underwent a large volume lumbar puncture and
12 h later was greatly improved, both cognitively and in terms
of mobility. He stated, “I feel like I’ve crawled out of my own
grave.” As expected, this improvement was short-lived, but he
underwent VP shunting and the improvement returned and
was durable for approximately 2 years, though he recently
passed away in home hospice care.
One final patient with NPH suffered a small left parietal
intracerebral hemorrhage at age 69 and then a small right
temporal lobe hemorrhage at age 75. He recovered well from
each hemorrhage but had progressive memory and gait impairment throughout this time. At age 77, an MRI was obtained showing ventriculomegaly and cerebral microhemorrhages
(Fig. 2e, f). He consequently underwent a large volume lumbar puncture for evaluation of normal pressure hydrocephalus
and had no substantial change in mobility, incontinence, or
cognitive, either objectively or by the family’s subjective

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Fig. 2 Normal pressure hydrocephalus and cerebral amyloid angiopathy.
a MRI from a patient with a clinical syndrome of normal pressure
hydrocephalus just prior to ventriculoperitoneal shunting. b The CT
scan at age 91 showed two tiny acute hemorrhages and ventricular
catheter with reduced ventricular size. c At post-mortem analysis, he
was found to have hundreds of cerebral microhemorrhages of varying
age. d Microscopy through the full thickness of the occipital cortex (far

right) demonstrated β-amyloid deposition (methoxy-XO4, green) in most
penetrating arterioles and some capillaries (vascular endothelium stained
in red with FITC-lectin) in the cortex sparing the white matter consistent
with type 1 CAA. e T1-weighted MRI shows ventriculomegaly in another
patient with normal pressure hydrocephalus and f GRE-T2* images show
typical changes associated with cerebral amyloid angiopathy

assessment. The failure to improve was attributed to the
longstanding nature of his symptoms. He died at age 81 from
aspiration related to progressive dysphagia.

animals as he could in 60 s, he responded slowly, “Rabbit ....
uh … anything that moves ... let’s see.... all sorts of things that
get around”). Object naming on the short form of the Boston
Naming Test was impaired at 2.7 standard deviations below
the mean; there were paraphasic errors without neologisms. A
brain MRI showed enlarged ventricles and a pattern of cerebral microhemorrhages characteristic of CAA (Fig. 3). He was
treated with acetylcholinesterase inhibitors which neither he
nor his family felt were helpful.
Our final case was that of a gentleman with a medical
history of depression and recurrent spontaneous pneumothoraxes due to bullous emphysema, complicated by delirium. He
presented to neurological care at age 71 when he developed
diplopia after a fall. At this evaluation, his family complained
that he had developed short-term memory loss gradually over
the preceding decade, was unable to manage finances, and
was having trouble driving. His MMSE was 25. He had nightmares, often about snakes, for the prior 2–3 years with occasional thrashing in his sleep and acting out vivid dreams. He
also complained of intermittent left-hand numbness.
Neuropsychological testing confirmed moderate impairments
in executive functioning, memory, and visual perceptual reasoning. An MRI of the brain was unremarkable, aside from
scattered white matter hyperintensities. He had progressive
worsening of mood symptoms (family was astonished when
he seemed uninterested after the birth of a grandchild), and his
symptoms overall fluctuated dramatically from day-to-day.

Lewy Body Dementia
The diagnosis of probable Lewy body dementia was made in
this 80-year-old gentleman independently by a senior psychiatrist, a cognitive neurologist, and a neuropsychologist, prior
to obtaining an MRI with evidence of CAA. His symptoms
began around age 70 and came to clinical attention at about
age 76, after approximately 2 years of cognitive and psychiatric decline. This followed a car accident in which he
sustained a small subdural hemorrhage. His deficits seemed
greatly out-of-proportion to the trauma he sustained,
prompting our evaluation. He had significant deficits in
short-term memory, orientation, and language, with prominent
difficulty with naming and repetition. Additionally, he suffered from paranoia, nightmares, and non-antagonistic hallucinations. He would often forget that deceased family members were no longer living. His family reported a decline in his
sense of humor. He had inappropriate spending habits and
acquired a substantial credit-card debt. While he did not provide a history of falls, his gait was broad-based and unsteady.
His MMSE was 9/30, and he had deficient semantic and phonemic fluency (for instance, when asked to name as many zoo

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Fig. 3 Lewy body dementia with cerebral amyloid angiopathy. This patient who was clinically diagnosed with Lewy body dementia had extensive white
matter hyperintensities on FLAIR (left two images) and scattered cerebral microhemorrhages in a pattern typical of cerebral amyloid angiopathy

He had terrifying visual hallucinations, often of snakes, and
had an emergence of sexually inappropriate behavior, treated
effectively with progesterone. The REM behavior disorder
symptoms improved for a while with treatment with clonazepam, although he continued to have occasional injuries, once
when he thought he was leaping from a car and jumped out of
bed, striking his head. By age 74, his gait was slowed, he
developed a hunched posture, lost his sense of smell, and
became physically aggressive. He moved into a memory care
center and continued to hallucinate, thinking he was in a war
zone, or that he was incarcerated, or that his wife was unfaithful to him. Later that year, he required several psychiatric
hospitalizations for hallucinations and suicidality, and he
was eventually treated with ECT which had limited beneficial
effect. He expired shortly thereafter. His autopsy was striking
for the complete absence of Lewy bodies, absence of βamyloid plaques or neurofibrillary tangles; the only neuropathology observed was CAA.

Discussion
Of the cases discussed, all received the diagnosis of CAA after
presenting with a classical clinical dementia syndrome not
typically associated with CAA: primary progressive aphasia,
dementia with Lewy bodies, or normal pressure hydrocephalus. These cases were selected because they are striking and
illustrate the range of presentations which can be associated
with CAA. These cases also raise hypotheses regarding disease mechanisms.
CAA is frequently comorbid with AD and 36% of patients
with AD also have cerebral microhemorrhages [23, 24].
Cerebral microhemorrhages have been described in primary
progressive aphasias in three prior studies and are particularly
linked to the logopenic variant [25, 26, 27••]. In these studies,
the prevalence of cerebral microhemorrhages ranged from 30
to 50%, and the distribution tended to be lobar, in a pattern
typical of CAA. Both logopenic variant primary progressive

aphasia and CAA are associated with AD pathology; thus, it is
not clear whether CAA contributes to the clinical presentation
or is a bystander. In the final case, it is striking that the patient’s language symptoms preceded the hemorrhagic pathology by several years; yet, all of the hemorrhagic changes
occurred in brain areas relevant to language function, suggesting that the underlying vasculopathy may be a driver of the
symptoms even prior to hemorrhage. All three of our cases
had focal CAA-related hemorrhagic and/or atrophic changes
in areas of the brain associated with language function, which
suggests the hypothesis that CAA can directly contribute to
primary progressive aphasia, although this will need to be
evaluated in a larger study with a neuropathological
confirmation.
A significant proportion (33 to 70%) of patients with LBD
have some neuropathological evidence of CAA, and 13 to
20% have severe CAA (which we would expect to detect on
MRI) [5, 28, 29]. While this association has been consistently
documented over several decades, there remains little insight
into how or whether CAA contributes to the pathobiology and
symptomatology of LBD. However, emerging data confirms
our clinical observation that distressing hallucinations are an
underrecognized symptom of severe CAA and can adversely
impact patient and family quality of life [30••].
Finally, a recent study found that 9% of biopsies performed
for NPH also showed CAA [31•]. The pathological mechanism
of NPH is poorly understood, making it difficult to predict the
role of CAA in this process. However, it is understood that posthemorrhagic conditions (subarachnoid hemorrhage, trauma,
and some intraparenchymal hemorrhages) may be complicated
by a communicating hydrocephalus with normal or low pressure, which has been attributed to scarring of the arachnoid
granulations. It is possible that the microhemorrhagic changes
of CAA recapitulate this mechanism. It is not known whether
acute blood circulating within the CSF, or hemoglobin
breakdown products, or products of oxidative stress related to Fenton-cycling of the elemental iron released
during hemoglobin breakdown are the essential steps in

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leading to NPH, but these mechanisms are all active in
patients with CAA [32]. The issue is also important because CAA may be considered to carry an increased risk
of bleeding with shunt procedures.

Curr Neurol Neurosci Rep
7.

8.
9.

Conclusions
These clinical observations demonstrate that CAA can have a
varied presentation complicating the differential diagnosis of
dementia syndromes and may share and/or contribute to the
pathological mechanisms underlying a variety of neurodegenerative disorders. The mechanistic links between AD, LBD,
NPH, and CAA remain incompletely understood.
Nevertheless, recognizing the breadth of CAA’s clinical associations is necessary to ensure effective treatment and to guide
further inquiry into its mechanism.

10.

11.

12.

13.

14.

Compliance with Ethical Standards
15.
Conflict of Interest Carolyn Akers, Lealani May Y. Acosta, Ciaran
Considine, Daniel Claassen, Howard Kirshner, and Matthew Schrag each
declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.

16.

17.

18.

References
19.

Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1.
2.

3.

4.

5.

6.

Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke.
1987;18:311–24.
Zabel M, Schrag M, Crofton A, Tung S, Beaufond P, Van Ornam J,
et al. A shift in microglial β-amyloid binding in Alzheimer’s disease is associated with cerebral amyloid angiopathy. Brain Pathol.
2013;23:390–401.
Alonzo NC, Hyman BT, Rebeck GW, Greenberg SM. Progression
of cerebral amyloid angiopathy: accumulation of amyloid-beta40 in
affected vessels. J Neuropathol Exp Neurol. 1998;57:353–9.
Passiak BS, Liu D, Kresge HA, Cambronero FE, Pechman KR,
Osborn KE, et al. Perivascular spaces contribute to cognition beyond other small vessel disease markers. Neurology. 2019;92:
e1309–21.
Schrag M, Greer DM. Clinical associations of cerebral microbleeds
on magnetic resonance neuroimaging. J Stroke Cerebrovasc Dis.
2014;23:2489–97.
Schrag M, McAuley G, Pomakian J, Jeffry A, Tung S, Mueller C,
et al. 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.

20.

21.

22.

23.

24.

25.

26.

(2019) 19:64

McAuley G, Schrag M, Barnes S, Obenaus A, Dickson A,
Holshouser B, et al. Iron quantification of microbleeds in postmortem brain. Magn Reson Med. 2011;65:1592–601.
Schrag M, Kirshner H. Neuropsychological effects of cerebral amyloid angiopathy. Curr Neurol Neurosci Rep. 2016;16:76.
Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and
complications in the aging brain. II. The distribution of amyloid
vascular changes. Stroke. 1983;14:924–8.
Charidimou A, Boulouis G, Gurol ME, Ayata C, Bacskai BJ,
Frosch MP, et al. Emerging concepts in sporadic cerebral amyloid
angiopathy. Brain. 2017;140:1829–50.
Jellinger KA, Attems J. Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease. J Neurol Sci. 2005;229–230:
37–41.
Nicoll JAR, Yamada M, Frackowiak J, Mazur-Kolecka B, Weller
RO. Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer’s disease: pro-CAA position statement.
Neurobiol Aging. 2004;25:589–97.
Boyle PA, Yu L, Nag S, Leurgans S, Wilson RS, Bennett DA, et al.
Cerebral amyloid angiopathy and cognitive outcomes in
community-based older persons. Neurology. 2015;85:1930–6.
Mesker DJ, Poels MM, Ikram MA, Vernooj MW, Hofman A,
Vrooman HA, et al. Lobar distribution of cerebral microbleeds:
the Rotterdam Scan Study. Arch Neurol. 2011;68:656–9.
McCarron MO, Nicoll JAR. Cerebral amyloid angiopathy and
thrombolysis-related intracerebral haemorrhage. Lancet Neurol.
2004;3:484–92.
Charidimou A, Boulouis G, Roongpiboonsopit D, Auriel E, Pasi M,
Haley K, et al. Cortical superficial siderosis multifocality in cerebral
amyloid angiopathy. Neurology. 2017;89:2128–35.
Charidimou A, Jager RH, Fox Z, Peeters A, Vandermeeren Y,
Laloux P, et al. Prevalence and mechanisms of cortical superficial
siderosis in cerebral amyloid angiopathy. Neurology. 2013;81:626–
32.
Malhotra A, Schindler J, Mac Grory B, Chu S, Youn TS, Matouk C,
et al. Cerebral microhemorrhages and meningeal siderosis in infective endocarditis. Cerebrovasc Dis. 2017;43:59–67.
Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird AH,
Richardson EP Jr. Cerebral amyloid angiopathy without and with
cerebral hemorrhages: a comparative histological study. Ann
Neurol. 1991;30:637–49.
Kirshner HS, Bradshaw M. The inflammatory form of cerebral
amyloid angiopathy or “cerebral amyloid angiopathy-related inflammation” (CAARI). Curr Neurol Neurosci Rep. 2015;15:54.
Renard D, Wacongne A, Thouvenot E. Radiologically isolated cerebral amyloid angiopathy-related inflammation. J Stroke
Cerebrovasc Dis. 2017;26:e218–20.
Carlson C, Estergard W, Oh J, Suhy J, Jack CR Jr, Siemers E, et al.
Prevalence of asymptomatic vasogenic edema in pretreatment
Alzheimer’s disease study cohorts from phase 3 trials of
semagacestat and solanezumab. Alzheimers Dement J Alzheimers
Assoc. 2011;7:396–401.
Whitwell JL, Kantarci K, Weigand SD, Lundt ES, Gunter JL, Duffy
JR, et al. Microbleeds in atypical presentations of Alzheimer’s disease: a comparison to dementia of the Alzheimer’s type. J
Alzheimers Dis. 2015;45:1109–17.
Kirsch WM, McAuley G, Holshouser B, Petersen F, Ayaz M,
Vinters HV, et al. Serial susceptibility weighted MRI measures
brain iron and microbleeds in dementia. J Alzheimers Dis.
2009;7:599–609.
Whitwell JL, Jack CR Jr, Duffy JR, Strand EA, Gunter JL, Senjem
ML, et al. Microbleeds in the logopenic variant of primary progressive aphasia. Alzheimers Dement. 2014;10:62–6.
Whitwell JL, Lowe VJ, Duffy JR, Strand EA, Machulda MM,
Kantarci K, et al. Elevated occipital β-amyloid deposition is

Curr Neurol Neurosci Rep

(2019) 19:64

associated with widespread cognitive impairment in logopenic progressive aphasia. J Neurol Neurosurg Psychiatry. 2013;84:1357–
64.
27.•• Mendes A, Bertrand A, Lamari F, Colliot O, Routier A, Godefroy
O, et al. Cerebral microbleeds and CSF Alzheimer biomarkers in
primary progressive aphasias. Neurology. 2018;90:e1057–65. This
study links the logopenic variant of primary progressive aphasia to cerebral amyloid angiopathy (indicated by the presence of
lobar cerebral microhemorrhages) in a high percentage of
cases.
28. De Reuck J. The impact of cerebral amyloid angiopathy in various
neurodegenerative dementia syndromes: a neuropathological study.
Neurol Res Int. 2019;7247325.
29. Jellinger KA, Attems J. Cerebral amyloid angiopathy in Lewy body
disease. J Neural Transm. 2008;115:473–82.
30.•• Vik-Mo AO, Bencze J, Ballard C, Hortobágyi T, Aarsland D.
Advanced cerebral amyloid angiopathy and small vessel disease
are associated with psychosis in Alzheimer’s disease. J Neurol
Neurosurg Psychiatry. 2018:318445. https://doi.org/10.1136/jnnp-

Page 7 of 7

64

2018-318445. This is the first report of a strong connection
between severe cerebral amyloid angiopathy and psychosis,
an issue we have confronted frequently in clinical practice.
31.• Pomeraniec IJ, Taylor DG, Bond AE, Lopes MB. Concurrent
Alzheimer’s pathology in patients with clinical normal pressure
hydrocephalus. J Neurosurg Sci. 2018. https://doi.org/10.23736/
S0390-5616.18.04350-3. This study demonstrated that
cerebral amyloid angiopathy is present in 9% of brain
biopsies from patients with normal pressure hydrocephalus.
32. Schrag M, Crofton A, Zabel M, Jeffry A, Kirsch D, Dickson A, et al.
Effect of cerebral amyloid angiopathy on brain iron, copper, and zinc
in Alzheimer’s disease. J Alzheimers Dis. 2011;24:137–49.
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