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Published in final edited form as:
Neurocase. 2010 February ; 16(1): 15–22. doi:10.1080/13554790903193174.
Alzheimer Disease Neuropathologic Changes in Semantic
Dementia
Tiffany Chow, MD, MSc1,2, Arousiak Varpetian, MD3, Taryn Moss, BA4, Harry V. Vinters,
MD5, and Carol Miller, MD6
1Baycrest Rotman Research Institute
2University
of Toronto Department of Medicine, Division of Neurology, Department of Psychiatry,
Division of Geriatric Psychiatry; and Baycrest Division of Neurology
3Rancho
4Ryerson
Los Amigos National Rehabilitation Center
University
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5University
of California at Los Angeles Alzheimer’s Disease Center
6University
of Southern California Alzheimer’s Disease Research Center and USC Alzheimer’s
Research Center of California
Abstract
Neuropathologic change underlying primary progressive aphasia (PPA) most commonly includes
one of the frontotemporal lobar degenerations, such as FTLD-tau or FTLD-ubiquitin. The next
most frequent etiology of PPA is Alzheimer’s disease (AD). We describe 5 subjects with clinical
diagnoses of semantic dementia, who underwent longitudinal clinical evaluation and postmortem
neuropathology examination of the central nervous system. This case series examines
retrospectively which clinical parameters might have pointed to the neuropathological diagnosis of
AD.
Conclusion—Family history of late onset dementia, APOEε4 status, combined features of
semantic dementia and progressive non-fluent aphasia present early in illness, or generalized
seizures, may indicate AD as the underlying pathology of semantic dementia.
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Dementia of the Alzheimer type (DAT) is frequently in the differential diagnosis for the
syndrome of semantic dementia (SD). There is significant overlap in clinical presentations
of SD due to frontotemporal lobar degeneration (FTLD) or neuropathologically proven
Alzheimer’s disease (AD).(Varma, Snowden, Lloyd et al.) Semantic difficulties of SD are
concomitant with early episodic memory impairment,(Hodges & Patterson, 1995) and ages
at onset can be similarly late in life.(Chow, Boone, Mishkin, & Miller, 2001) Patients in
later decades of life have an increased risk of showing AD pathologic change either along
with or instead of frontotemporal lobar degeneration with either tau- or ubiquitinimmunoreactive inclusions (FTLD-tau, FTLD-U).
At the time of diagnosis of the subjects in this study, clinical criteria for primary progressive
aphasia (PPA) were classified as two types: progressive non-fluent aphasia (PNFA) and
semantic dementia (SD). (McKhann et al., 2001; Neary & al., 1998) Since then, a third type
of aphasic syndrome has been described by consensus; logopenic progressive aphasia
(LPA).(Gorno-Tempini, Brambati, Ginex et al., 2008; Gorno-Tempini, Dronkers, Rankin et
Please send all correspondence to: Tiffany Chow, MD, Rotman Research Institute, Baycrest, 3560 Bathurst Street, 8th Floor, Brain
Health Complex, Toronto, ON M6A 2E1, Canada, 416-785-2500 x3459, FAX 416-785-2862, tchow@rotman-baycrest.on.ca.
Chow et al.
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al., 2004; Kertesz & Munoz, 1997). LPA may resemble semantic dementia in that patients
with LPA remain fluent with severe anomia. However, this type of FTD may be more
frequently attributable to regional AD pathologic change than to FTLD-tau or FTLD-U.
(Gorno-Tempini et al., 2004) We conducted a retrospective chart review to explore clinical
details that might have distinguished those patients with semantic dementia due to
neuropathological AD.
METHODS
This retrospective chart review was approved by the University of Southern California
Health Sciences Campus Institutional Review Board. We selected subjects who had
completed autopsy by January, 2008, and who had been diagnosed with semantic dementia
(SD). Subjects were clinically diagnosed with SD by a single clinician (TWC) using
consensus criteria (McKhann et al., 2001; Neary & al., 1998) at the Rancho Los Amigos
Alzheimer’s Center of California and underwent autopsy at the Neuropathology Cores of the
USC Alzheimer’s Disease Research Center or the UCLA Alzheimer’s Disease Center.
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We accessed clinical records, including clinician notes and prior correspondence with
caregivers describing subject symptomatology, as well as results of neuroimaging and
clinical laboratory tests. Data extracted from the charts onto coded data collection sheets
included demographics, timing of onset of illness, and features of the aphasia described by
Neary, (Neary & al., 1998) McKhann, (McKhann et al., 2001) and Gorno-Tempini.(GornoTempini et al., 2004) Included were diagnostic criteria for PNFA, SD, and LPA, if available,
from the first 5 years of illness see; and also neuropsychiatric profiles; neuroimaging
findings; neuropsychological evaluations; and neuropathologic findings.
We then re-assessed whether, over the course of illness, the cases met criteria for PPA and
correlated those retrospective clinical diagnoses with the neuropathologic diagnoses. The
number of cases was too small (n =5 SD) to conduct meaningful statistical analyses.
RESULTS AND CASE SUMMARIES
All 5 subjects were men. None of the cases met criteria for apraxia of speech (AOS) as
described by Josephs et al.: slow speaking rate, abnormal prosody and distorted sound
substitutions, additions, repetitions and prolongations, sometimes accompanied by groping
and trial and error articulatory movements (Josephs, Duffy, Strand et al., 2006). Patients
with SD were treated with cholinesterase inhibitors, considering the likelihood that they had
atypical AD, but language did not improve with this intervention.
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CASE SUMMARIES
FM presented to the Behavioral Neurology Clinic at age 56, 10 years after new onset of
stuttering. He made phonemic and semantic errors during fluent, empty speech with anomia
and eventually was not able to follow commands. It is possible that he had apraxia but, by
the time of presentation, he was too impaired for neuropsychological testing. Even in
retrospect, the patient’s wife reports that he didn’t lose much memory, citing as examples
retained wayfinding, even in another city, long after the patient was unable to speak or
participate in simple chores. At ten years into his illness, he displayed aggressive behavior
and sexual disinhibition. Later into the illness, he had 2 generalized tonic-clonic seizures.
SPECT scan showed left-sided hypoperfusion that included frontal, temporal and parietal
regions (see Figure 1). Although the SPECT scan showed parietal involvement which may
have been indicative of AD, the patient’s early onset age, long history of primary aphasia
follwed by major disinhibition (e.g., urinating into the sink in the clinical exam room during
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a follow-up appointment) seemed to fit SD more so than AD. The patient died after 13 years
of illness.
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The neuropathologic diagnosis was AD with rarefaction of temporal white matter. The
distribution of neuropathologic changes was more often symmetrical than asymmetrical.
Atrophy was moderate throughout the brain, including the hippocampal regions. Diffuse
plaques were frequent in bilateral mid frontal, bilateral superior and middle temporal, left
inferior parietal, right primary visual, right visual association cortices; sparse in the right
hippocampus. Neuritic plaques were frequent in both frontal, both temporal, left inferior
parietal, and right visual association cortices. Neurofibrillary tangles were frequent in left
middle frontal and both superior and middle temporal cortices, and right hippocampus. The
right hippocampus also featured moderal granulovacuolar degeneration and Hirano bodies.
Although he had manifested fasciculations in his lower extremities during life, he did not
have motor neuron disease (MND) pathology, or ubiquitinated neuronal cytoplasmic
inclusions by immunohistochemistry.
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DO presented to clinic at age 66, 3 years after initial onset with difficulty reading aloud.
Symptoms of depression were apparent before his language declined. The depression may
have been related to diagnosis of lung cancer, but the tumor was resected successfully. His
family noted a decline in language shortly after the surgery. His speech was fluent and
empty, with phonemic and semantic paraphasias and impaired naming and understanding.
Formal neuropsychological testing was attempted but could not be completed due to the
severity of his language deficits. Also because of this aphasia, it was difficult for the family
to tell whether he had significant memory loss. Four years into the illness, he was engaging
in bathing rituals, had increased appetite, and developed bowel and bladder incontinence.
One year after that, he had a generalized tonic-clonic seizure. Over the course of the illness,
he developed cogwheeling, rigidity, and resting tremor, as well as displaying frontal release
signs. Brain imaging showed predominantly temporal lobe atrophy. Family history included
a father with late onset dementia. Similar to FM, he had fasciculations in his lower
extremities clinically, but did not have MND pathology. The early onset age, predominance
of progressive aphasia, early incontinence, and onset of obsessive-compulsive behaviors
midway into illness led to the diagnosis of SD over AD.
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After 10 years of illness, DO came to autopsy. Neuropathologic diagnosis was AD with
severe atrophy of the frontal and temporal lobes and moderate atrophy elsewhere, including
the hippocampus. Diffuse plaques were more frequent in the left than right middle frontal,
right more than left superior and middle temporal, right more than left inferior parietal, and
right more than left primary visual cortex. Neuritic plaques were frequent in both superior
and middle temporal regions, the left inferior parietal and the left visual association cortex.
Neurofibrillary tangles were frequent in all cortical sections except for absence from left
primary visual and visual association cortex. Neurofibrillary tangles were frequent in all
cortical sections except for absence from left primary visual and visual association cortex.
TDP-43 immunostain of frontal, temporal, parietal and occipital neocortices revealed no
inclusions. The hippocampus, including dentate granule neurons and pyramidal neurons,
was immunoreactive. No positive inclusions were present in the basal ganglia (putamen,
globus pallidus); mesencephalon; pons; cerebellum; or spinal cord (cervical, thoracic, and
lumbar). There was moderate, diffuse, nonspecific immunostain of neurons of the basal
pontis and anterior horn cells. The neuropathologic findings, plus the clinical dementia
fulfilled the NIA/Reagan criteria for high probability Alzheimer’s disease using NIA/
Reagan criteria.
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LA presented at age 58, 5 years after onset with problems with expressive language and
word finding. Single word repetition was intact, but he had impaired comprehension of word
meaning, prosopagnosia and associative agnosia, and later developed hypophonia. He and
his wife denied memory loss as a symptom long into the course of illness, citing aphasia as
the main problem. He was unable to execute learned purposeful movements (ideomotor
apraxia). Serial MMSE scores declined 2–3 points per year over the next 4 years. He
developed a quick temper and was also inappropriately affectionate with female
acquaintances. He had symptoms of depression and anxiety related to retained insight
signaling his aphasia and the poor prognosis for recovery. Brain MRI showed atrophy of the
left frontal lobe. He had a sister who suffered from depression and a maternal uncle with
ALS. This family history, along with early onset of predominant progressive aphasia for
which the patient had good insight, and development of disinhibition highly uncharacteristic
of his baseline indicated SD more than AD.
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The patient died after 13 years of illness and the neuropathologic diagnosis was AD with
amyloid angiopathy. Atrophy was rated as mild, with no specific asymmetry. Diffuse
plaques were frequent in both superior and middle temporal, and the left inferior parietal
regions, while neuritic plaques were more lateralized to the left superior and middle
temporal, left inferior parietal and left lateral geniculate body. Neurofibrillary tangles were
frequent in left middle frontal, bilateral superior and middle temporal, and bilateral
hippocampal regions. TDP-43 immunohistochemistry showed no reactivity of any
neocortical regions (frontal, parietal, temporal, occipital). The basal ganglia, brainstem
(mesencephalon, pons, and medulla) and spinal cord neurons revealed TDP-43 positive
inclusions. The neuropathologic findings, combined with a clinical history of dementia were
consistent with a high probability of Alzheimer’s disease.
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MC presented at age 70, 1 year after onset of anomia. Repetition was intact, but he had
impaired comprehension of word meaning and low average scores on tests for associative
agnosia. MMSE scores declined precipitously from 20 to 0 out of 30 in only 2 years due to
profound impairment in comprehension. He developed separation anxiety, irritiability, and
amotivational syndrome within the first year of illness. Memory loss was only apparent
more than halfway into the course of illness. The patient used to recount stories of his days
which were difficult to comprehend due to the absence of key nouns. His wife, however,
was able to understand what he meant and corroborated the relative accuracy of the stories.
Brain MRI showed mild atrophy at presentation. SPECT scans revealed left parietal
hypoperfusion extending to the ipsilateral temporal lobe and perisylvian fissure. He had a
fall with subdural hematoma 3 years into illness. A generalized seizure late that same year
was attributed to subtherapeutic levels of phenytoin prescribed after the evacuation of a
subdural hematoma. MC’s mother had died with a late onset dementia. Despite the later
onset age and parietal hypoperfusion indicating AD in this patient, the length of
predominantly progressive aphasia as the sole symptom, his persistent euphoria through
much of the illness, and the relative retention of memory function were interpreted as SD,
not AD.
After 10 years of illness, the neuropathologic diagnosis was AD. There was severe atrophy
in the frontal and temporal lobes. Diffuse plaques were frequent in frontal, temporal, parietal
regions, with neuritic plaques more frequent in the superior and middle temporal and
hippocampal than in frontal or parietal regions. Neurofibrillary tangles were frequent in
superior and middle temporal, hippocampus and entorhinal cortex. There was no comment
to support an asymmetry of neuropathologic changes. TDP-43 immunostaining of frontal,
temporal, parietal and occipital cortices revealed moderate to strong but diffuse staining of
pyramidal neurons, particularly the nuclei. Hippocampal neurons, including dentate-granule
cells and pyramidal neurons were negative. No neuronal inclusions were noted, here or in
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the brainstem and spinal cord. The clinical history of dementia plus neuropathologic changes
was consistent with high probability Alzheimer’s disease according to NIA/Reagan criteria.
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LR presented at age 69, 3 years after the onset of anomia. Single word repetition was intact,
but he had impaired naming and comprehension without prosopagnosia or associative
agnosia. He developed alexia rather quickly, yet remained able to compose music (his
vocation) until year 6 of his illness. Serial MMSE scores fluctuated from 29 to 22 to 25 to 19
over years 1–5 of illness. He became very self-absorbed, arrogant and distractible over time.
He retained insight about his aphasia and poor prognosis for recovery far into the illness.
The aphasia made it difficult for his wife to recognize memory loss, but memory loss and
disorientation were clear after the 8th year of illness. The example given was that he could
no longer play music he had composed on the piano, even the one tune on which he had
come to perseverate earlier in the illness. Inability to recognize his own son, even with cuing
may have represented visuoperceptive difficulties. His wife had the impression that he
would sometimes pretend to remember a person or story after being reminded, yet it was
clear he really did not. Specific recognition of his wife was impaired by year 11 of illness;
he indicated that she was familiar and someone he was happy to see. At that point, he had
lost interest in dogs, otherwise a long time passion but sought cigarettes to the end of his
life.
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Brain MRI showed atrophy of the left temporal lobe (see Figure 2). He had a brother who
suffered from depression. This patient ranged to the older end of early onset but his ability to
compose music far into the progressive aphasia course and frontal behavioral features led to
the diagnosis of SD more than AD. His course lasted long enough that a potential diagnosis
of AD was discussed with his family after the first 10 years of illness.
After 12 years of illness, the neuropathologic diagnosis was FTLD-U. Anti-TDP-43 and
ubiquitin immunostains detected 1) abundant intracytoplasmic inclusions in temporal and
frontal cortices and 2) both intranuclear and neuritic inclusions in hippocampal regions.
Of five subjects clinically diagnosed with SD, four were pathologically diagnosed with AD
and one had ubiquitinated inclusions (FTLD-U). All APOEε4-positive SD cases (3/5) had
AD. The FTLD-U case had no APOEε4 allele. Despite the presence of APOEε4, family
histories did not consistently raise suspicion for AD. Two of the four AD subjects had a
parent with late onset dementia. One subject with AD and the one with FTLD-U each had a
sibling with depression. A subject with AD also had a maternal uncle with ALS.
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None of cases met more criteria for LPA than for SD. Those SD cases with AD pathology
were impaired in comprehension and repetition, while the subject with FTLD-U retained
repetition ability longer into course of illness. In two AD subjects and the one with FTLD-U,
agraphia and alexia did not develop for most of the illness. Characteristic for AD was the
rate of progression of decline in the MMSE scores. Two with AD for whom MMSE
progression could be tracked lost 6–7 points over a 3 year period. A third with AD was
unable to respond to MMSE questions due to rapid progression of aphasia by year 3 or 4
into illness. The subject with FTLD-U had fluctuations in MMSE scores over a 5-year
period.
Behavioural disturbances were seen in some of the AD subjects: one subject with AD
developed sexual disinhibition; another engaged in bathing rituals and had increased
appetite. Subjects with AD had depression or mixed depression and anxiety preceding their
aphasia. This was erroneously interpreted as a pertinent negative finding of the belle
indifference associated with AD. The subject with FTLD-U demonstrated new selfishness
and arrogance.
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The five subjects clinically diagnosed with SD had more features atypical of SD rather than
features characteristic of AD. None reported any developmental delay or learning disorder. 3
of 4 with pathological AD made both phonemic (PNFA) and semantic (SD) paraphasic
errors on early examination. None of the five (including FTLD-U) met all Neary criteria for
SD (2 did not have perceptual disorder testing). Each AD subject met 2 or all 5 Neary
criteria for PNFA, in addition to aspects of SD. Also atypical for SD, 3 of the 4 subjects with
AD had generalized seizures. The one with FTLD-U did not have seizures. Atrophy on
neuroimaging was symmetrical in 2 of 4 subjects with AD, which is uncharacteristic of SD.
One of four subjects with AD lived longer than typically reported for SD (13 years instead
of 6–10), but the one with FTLD-U pathology also survived 12 years with illness.
There were also characteristics atypical of AD in the subjects with pathological diagnosis of
AD. Average age of onset of 62.5 years (range 56–70) in the 4 AD subjects was young. Age
of onset of the one with FTLD-U was age 69. The referring physician in only 1 of 4 AD
cases cited memory loss as a reason for referral, but this was in addition to anomia and
impairment in expressive language. Each subject retained insight into his aphasia which is
unusual for patients with AD.
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In addition, the four SD subjects diagnosed with AD at autopsy had certain pathological
features which were atypical of AD. Neuritic plaques were more dense in frontotemporal
than temporoparietal regions in one of three (FM); no neurofibrillary tangles were seen in
the parietal lobe of the same subject. Neuritic plaques and NFTs were moderate to severe in
hippocampus (CA1), frontal, temporal, and parietal cortices. Left vs. right hemisphere
comparisons for plaque burden were not available for all subjects, but two of three AD
subjects had asymmetric plaque burden and not both concentrated on the left. Parietal
atrophy was absent in one subject (LA).
DISCUSSION
Twelve previous studies address patients diagnosed clinically with PNFA or SD and who
were neuropathologically confirmed (see Table 1). Tallying all of the reported
clinicopathologic confirmations of FTLD shows more concordance in diagnosing SD (79%)
than PNFA (65%). Alzheimer’s disease pathology was the most frequent non-FTLD finding,
but AD with concomitant dementia with Lewy bodies has also been reported.
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We present 4 subjects with clinical diagnoses of SD and neuropathologic diagnoses of AD.
As previously reported for SD due to FTLD (Davies, Hodges, Kril et al., 2005; McMonagle
& Hodges, 2007), all 5 subjects with SD manifested behaviors typical of behavioral variant
frontotemporal dementia (bvFTD) by 5–6 years after the onset of illness, yet 4 of the 5 SD
subjects ultimately had AD. Behavioral disturbance therefore did not point accurately away
from a diagnosis of atypical DAT.
Retrospective diagnosis did not change from SD to LPA in the subjects with AD at autopsy,
and it remains unclear that this subtyping revels underlying pathology. Mesulam et al. found
AD pathology in many but not all (7 of 11) subjects with LPA.(Mesulam, Wicklund,
Johnson et al., 2008)
Although superior letter and category fluency may distinguish between AD and FTD
(whether tau negative or tau positive),(Grossman, Xie, Libon et al., 2008) this indicator did
not help anticipate the neuropathologic changes of AD in our study. The Repeat and Point
test has recently shown differentiation between SD and PNFA; further study may reveal
whether impairment on this test also betrays SD due to FTLD vs. AD.(Hodges, Martinos,
Woollams, Patterson, & Adlam, 2008)
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Lack of asymmetry on neuroimaging was inconsistently seen in the AD group, unlike
previously reported autopsy-confirmed SD cases with FTLD-U or Pick’s disease who show
asymmetry.(Davies et al., 2005)
Three of our 4 SD cases with AD pathology showed sparing of neuritic plaques in
hippocampus and entorhinal cortex relative to AD cases with typical presentations. We did
observe predominance of neurofibrillary tangle burden in the entorhinal cortex as
documented in typical AD elsewhere.(Galton, Patterson, Xuereb, & Hodges, 2000; Mesulam
et al., 2008) We report high AD neuropathologic burden in the left inferior parietal area, not
focused only in temporal regions. If this had been more apparent on imaging (e.g., SPECT
imaging early in course of illness), perhaps AD would have figured larger on the clinical
differential diagnosis. APOEε4 positive genotype seemed indicative in our small series of
AD pathology, but Mesulam et al. report FTLD pathology in a larger sample of PPA cases
despite APOEε4 positive genotype and mixed aphasia characteristics at presentation.
(Mesulam et al., 2008) Other indicators for AD risk were found in our series: family history
of late onset dementia and/or development of generalized seizures were present in some but
not all of the 4 subjects who had AD pathology. Further studies with larger numbers of cases
may show which of these characteristics are reliably predictive of AD as the underlying
pathology of semantic dementia.
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Certain limitations of this case series may account for the lower diagnostic accuracy rate
than reported in previous studies. Included are the variable phases of illness at presentation
and the resulting inconsistency of data available. Some subjects presented much later into
the course of illness, too late to evaluate initial aspects of their aphasia, with the illness itself
limiting evaluation. Formal neuropsychological and speech and language pathology
evaluations would have afforded a consistently full set of language descriptors and clinical
criteria. The systematic evaluation of patients with SD by Davies et al., for instance,
undoubtedly assisted in their higher clinical diagnostic accuracy of 89% in 18 cases.(Davies
et al., 2005) Evaluations for the presence of apraxia in the current study were uncertain late
in the courses of illness. It was mostly difficult to know how much impairment was
secondary to comprehension deficit, especially among the patients with SD. Other
investigators have formalized a battery for the evaluation of limb apraxia in PPA that would
have been helpful in follow-up of our sample.(Joshi, Roy, Black, & Barbour, 2003)
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Rogalski et al. have recorded 14.6% prevalence of learning disability in patients, with
double that of family members of index cases. (Rogalski, Johnson, Weintraub, & Mesulam,
2008) We did not find histories of learning disability in any of the subjects in this study, but
their family histories of learning disability were not collected. Either small sample size or
missing data may account for this difference from the other study. It remains unclear
whether this aspect of clinical characterization might assist in differentiating between SD
due to FTLD vs. AD pathology.
Subjects in this study enjoyed prolonged survival after diagnosis, compared with the
reported 6–7 year survival rate in FTD (Roberson, Hesse, Rose et al., 2005). The survival of
our subjects exceeded even the prolonged survival reported for SD vs. bvFTD (Davies et al.,
2005; Roberson et al., 2005). Since AD generally has a longer course of illness, longer
survival might have been a clue to SD with AD pathology in this sample, but long survival
has been reported among a subgroup of patients with FTD.(Johnson, Diehl, Mendez et al.,
2005) The 2 subjects with SD due to AD described by Davies et al. had relatively young
onset ages, perhaps confirming that age at onset and survival are not likely to predict which
SD cases have underlying AD (Davies et al., 2005).
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CONCLUSION
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The current diagnostic criteria for semantic dementia have been shown in previous studies
and the current one to be non-specific for FTLD-U, corticobasal degeneration or Pick’s
disease. Given that AD belongs high on the differential diagnosis for semantic dementia,
risk factors for AD such as family history of late onset dementia and APOE genotype may
help determine whether interventions for AD should be part of the management plan for a
patient with semantic dementia.
Acknowledgments
We are grateful to the patients and families who generously participated in this study, expressly to help others
affected with frontotemporal dementias. We also thank Dr. Daniel Geschwind and the Genetics Core of the UCLA
Alzheimer’s Disease Center for APOE genotyping. This work was funded by NIA Alzheimer’s Disease Research
Center Grant Numbers P50 AG05142, P50 AG16570, and P30 AG08017; and Department of Health Services,
Alzheimer’s Research Center of California Grant No. 94-20356 (TWC, AV, CM), the University of Toronto Dean's
Fund for New Faculty (#457494 TWC), and an endowment to the Sam and Ida Ross Memory Clinic (TWC), and
the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine (HVV).
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Neurocase. Author manuscript; available in PMC 2011 March 7.
Chow et al.
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NIH-PA Author Manuscript
Figure 1.
Three-dimensional reconstruction of HMPAO-SPECT for subject FM, who had clinical
diagnosis of semantic dementia and AD at pathology. Scan shows predominantly left-sided
hypoperfusion involving temporal lobe with extension to frontal and parietal regions.
NIH-PA Author Manuscript
NIH-PA Author Manuscript
Neurocase. Author manuscript; available in PMC 2011 March 7.
Chow et al.
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NIH-PA Author Manuscript
Figure 2.
T1-weighted sagittal MRI for subject LR, who had clinical diagnosis of semantic dementia
and FTLD-U at pathology. Marked atrophy in left temporal lobe with extension to frontal
and parietal regions.
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Neurocase. Author manuscript; available in PMC 2011 March 7.
Chow et al.
Page 12
Table 1
Review of prior clinicopathological correlation studies.
NIH-PA Author Manuscript
Number of SD
Subjects in
Sample, %
Confirmed as
FTLD
Number of PNFA
Subjects in Sample,
%
of Confirmed as
FTLD
Non-FTD Dx’s at
Autopsy
Davies, RR et al.(Davies et al., 2005)
18, 89%
n/a
AD
Godbolt, AK et al.(Godbolt, Josephs, Revesz et al., 2005)
7, 100%
n/a
n/a
Josephs, KA et al. (Josephs, Whitwell, Duffy et al., 2008)
3, 100%
n/a
AD
Mandell, AM et al. (Mandell, Alexander, & Carpenter, 1989)
1, 100%
n/a
n/a
Knibb, JA et al. (Knibb et al., 2006)
15, 66%
23, 65%
AD
Kertesz, A et al.* (Kertesz et al., 2007)
2, 100%
20, 100%
n/a
1, 0%
17, 58.8%
AD
Takao, M et al. (Takao, Tsuchiya, Mimura et al., 2006)
n/a
1, 100%
n/a
Mochizuki, A et al. (Mochizuki, Ueda, Komatsuzaki et al., 2003)
n/a
1, 100%
n/a
Authors Names (reference)
Mesulam, M et al. (Mesulam et al., 2008)
NIH-PA Author Manuscript
Caselli, RJ et al. (Caselli, Beach, Sue, Connor, & Sabbagh, 2002)
n/a
1, 0%
AD with DLB
Li, F et al. (Li, Iseki, Kato et al., 2000)
n/a
1, 0%
AD with asymmetrical
brain atrophy
Scheltens, P et al. (Scheltens, Ravid, & Kamphorst, 1994)
n/a
1, 100%
n/a
*
All cases in this paper described as beginning as behavioral variant FTD.
NIH-PA Author Manuscript
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