A Longitudinal Case Study of an
Atypical Early-Onset Posterior Cortical
Dementia with Hyperostosis Frontalis Fernando Entenza, M.D., Univ. Central del Caribe, Puerto Rico
Maria T. Margarida-Julia Psy.D., Univ. de Puerto Rico
29th International Conference of Alzheimer Disease International
San Juan, Puerto Rico
May 1 - 4, 2014
Disclosures
Dr. Entenza
• No conflicts of interest
Dr. Margarida-Julia
• No conflicts of interest
No grants or other external funds used
Introduction
• Case study of an under-recognized focal
degenerative syndrome which
1. Describes its earliest manifestations
2. Exemplifies the benefits of a multidisciplinary evaluation
3. Calls attention to special needs of this population
4. Raises questions about the nature of PCA & HFI
Background Information
❖ Right handed
❖ 54 year-old married man
❖ Doctorate degree
❖ Highly specialized
professional
❖ Under my care since age 43
❖ Presented for treatment of
Bipolar Disorder
❖ Diagnosed Bipolar Disorder
Type I at the age of 35
❖ Claimed mood cycling since
age 21
❖ Medical conditions
❖ Metabolic syndrome
❖ Obesity
❖ Insulin-requiring DM-II
❖ Arterial hypertension
❖ Hypercholesterolemia
❖ Obstructive sleep apnea (using CPAP)
❖ Lumbar HNP
Family History
❖ Paternal grandfather
❖ Suspected AD
❖ Father
❖ Died due to AD in his 70's
❖ Apparent early-onset
❖ Older sister (58)
❖ Undergoing dementia
evaluation
❖ Initial symptom was memory
loss
❖ Eldest daughter
❖ Atypical Bipolar Disorder
since age 17
❖ Another daughter
❖ High impulsivity
❖ Very poor judgment
❖ Possible mood cycling
1. Atypical 11-Year Course
BIPOLAR DISORDER
Worsening over the 11-year span
• Abnormally persistent mood cycling
• Mixed-manic or mixed-depressive
symptoms
• Abnormal auditory perceptions & ideas of
reference (occasional)
• Anxiety (associated with new workplace
challenges and with greater depressive
symptoms)
COGNITIVE SYMPTOMS
Insidious over the past 3 years
• Adapting to new work procedures &
routines, and driving routes
• Although learning proficiently in the end
• Navigation problems in familiar places
These were initially present only during
heightened depressive symptoms
Brief medical leave-of-absences in the last 3 years
Treatment
at Cognitive Evaluation
• Divalproex ER 2,750mg QHS
• Lamotrigine 200mg QD
• Bupropion XL 150mg a/w Bupropion SR 100mg QD
• Quetiapine XR 100 mg QAM + 300 mg QHS
• Clonazepam 0.25 mg QAM + 0.5 mg QHS
2. Findings
Normal
• Physical & neurological exams
• Dementia laboratory workup
• HbgA1c = 6.4%
• Ceruloplasmin level
• M.R.A.
• E.E.G
Abnormal
• APOE є 3-4 genotype
• MRI neuroanatomy
• PET regional brain metabolism
• Neuropsychological testing
Parietal Atrophy &
Hyperostosis Frontalis Interna Axial views
Coronal Oblique T1 views
Parietal Atrophy & Hypometabolism
PET - Coronal view
Parietal Hypometabolism (L > R) Brain FDG-PET
Axial views
Sagittal views
Parietal Hypometabolism and Atrophy
Axial views
Medial Temporal Lobe Unaffected
Hyperostosis Frontalis Interna Internal Growths
Source: http://www.annclinlabsci.org/content/34/2/206/F1.large.jpg
Headache Evaluation
8 Years Earlier at Age 46
Earlier stages of HFI prefrontal compression
and Parietal Atrophy
Source: Crutch SJ, et al. The Lancet Neurology. February 2012, Vol.11(2):170–178.
Healthy individuals Normal eye-tracking and fixation on
mostly relevant aspects of the scene
PCA patients (poor top-down guidance and control
of saccadic movements)
(1) May fixate on relatively
uninformative aspects of the
scene
(2) May miss important
contextual information
SCALED SCORES
Test EIWA-III (1) WAIS-III (2)
Full Scale IQ 84 (80-88) 14%
Below average
74 (70-79) 4%
Borderline
Verbal
Comprehension 95
82
Below average
Working Memory 98 82
Below average
Perceptual
Organization 83
70
Borderline
Processing
Speed 87
76
Borderline
SCALED SCORES
Test EIWA-III (1) WAIS-III (2)
Verbal IQ 86 Below aver. 81 Below aver.
Verbal Comprehension
Vocabulary
Similarities
Information
11
8
8
8
5
7
Working Memory
Arithmetic
Digit span
Letter-Number
Sequencing
9
10
10
6
7
8
Performance IQ 82 Below aver. 70 Borderline
Perceptual
Organization
Picture Completion
Block Design
Reasoning Matrix
9
8
4
5
6
4
Processing Speed
Digit Symbol-Coding
Symbol Search
7
8
5
6
Average scores = 9 – 11
(1) EIWA-III standardization for Puerto Rico, a translated version of WAIS
III, consists of 330 adults divided in 3 age groups (16 to 19, 20 to 44 and 60 to
64). The sample used the 2000 Puerto Rico census and it is stratified by
educational level). (Manual de Administración y Puntuación.
(2) WAIS-III was normalized using a representative U.S. sample of 2,450
adults. Hispanic subjects represented 12-13% of the test's normative sample.
Standardization and Norms Development, p. 19-35).
Neuropsychological Testing
GENERAL COGNITIVE FUNCTIONING
Test Score Range
MMSE 20/ 30 Dementia
MOCA 14 / 30 Dementia
INECO Frontal Screening 15.5 / 30 Frontal deficits
Dementia Rating Scale (DRS-2)
Initiation / Perseveration
SS
(standard
score): 3
PE 3; 1%
Severe
MEMORY FUNCTIONS
California Verbal Learning Test
II (CVLT-II)
Short-Term Free Recall
Short-Term Cued Recall
Long-Term Free Recall
Long-Term Cued Recall
Total Learning Curve (1-5)
-1
1
-1
1
-1
Below average
High average
Below average
High average
Below average
VERBAL FUNCTIONS
COWAT Verbal Fluidity (Total)
Animals
Fruits
Vegetables
13
10
8
7
Severe
Borderline
Below average
Below average
EXECUTIVE FUNCTIONS
Trail A
Trail B
67 sec
-
Severe
Severe
Wisconsin Card Sort
Total errors
Non-perseverative errors
Conceptual answers
Completed categories
< 55
93
< 55
0 / 6
1% Severe
47%
1% Severe
Severe
• Relatively preserved episodic
memory
• Significant problems with attention
and other executive functions
Neuropsychological
Testing
Most Significant Deficits
NEUROPSYCHOLOGICAL TESTING
Function Cognitive Test Level of Impairment
Visuo-spatial processing
EIWA-III Matrix subset
Moderate
MOCA cube & clock drawing
MMSE pentagons
Trails A (67 sec) & B (-)
(visual tracking)
Spatial memory INECO Spatial Working Memory subset Moderate
Non-Visual Executive functions:
Cognitive flexibility
Planning
Sustained & divided attention
INECO Motor Series
(motor programming)
Moderate INECO Go-No-Go
(inhibitory control)
Wisconsin Card Sorting Test
DRS-2 Initiation/Perseveration subset
Memory & Learning EIWA-III & INECO Frontal Screen
Mild CVLT-II
Verbal fluency, naming, comprehension COWAT
Verbal abstraction tasks Mild
Management & Outcome
Developments 1-year following DX
• Retirement
• Voluntarily stopped driving
• Acetylcholinesterase inhibitor
• Memantine
• Relocation to Central Florida
Improvements seen and reported
• Overall functioning and cognition
MOCA = 23 / 30 (from 14 / 30)
• Except for episodic memory &
visuospatial abilities
-1 clock number placement
-1 cube copy
-4 recall
• Quality-of-life
• Anxiety & depressive symptoms
• Successful regime reductions
• Quetiapine discontinued
• Clonazepam reduced
Before Rx
01 / 2013
Age 54
After Rx
10 / 2013
Age 55 Improved
Case Summary
• Premorbid chronic atypical
neuropsychiatric disorder
(bipolar disorder features)
• Metabolic syndrome
• Possible familial early-onset
dementia pattern
• APO E4 risk factor
• Early-onset insidious
degenerative disorder
• L > R (dorsal) parietal atrophy
and hypometabolism
• Spared medial temporal lobe
• Pre-existent HFI compressing
prefrontal areas
• Visuospatial + non-visual
executive deficits
• Subjective and objective
response to usual AD Rx
• But episodic retrieval-verbal
recall deficits are worsening over
time
• Without obvious hippocampus
pathology
3. PCA Patients’ Special Needs
• Neuro-ophthalmologic evaluation
• Elements of Balint syndrome like simultagnosia (visual field perception), optic apraxia
(reaching using vision), oculomotor apraxia (fixating eyes)
• Registration for financial and social benefits and services (SSDI, pension, DOT, etc.)
• Early safety measures (driving, machinery)
• Occupational therapy / sensory team evaluation
• Assistive equipment for the visually impaired (simplified displays, talking books and
watches)
• Peer-support groups and psychotherapy
• Take advantage of the preserved memory and insight
• Neuropsychological testing
• Tests relying on intact vision are not valid
• Memory tests/tasks will underestimate clinical progression
• This & other PCA phenotypes may resemble frontal lobe syndromes
CASE PCA HFI
Demographics 54 y/o MALE with metabolic
syndrome Early-onset
Post-menopausal, diabetic
FEMALE
Posterior atrophy &
hypometabolism YES YES NO
Visual processing
problems
Spatial memory
Visual tracking
(21) Visual perception
Spatial memory
Visual attention
Visuospatial reasoning
Possibly via
FEF compression
Frontal atrophy No functional evidence yet YES,
in later stages
Possibly via
frontal compression
Working memory YES Both spatial & non-spatial
(10), via DLPFC compression
Episodic memory /
retrieval
Relatively preserved
But worsening
Relatively preserved, but often
progressive NO
Other non-visual
executive
functions
•Cognitive flexibility
•Planning
•Sustained & divided attention
•Motor programming
No evidence
(21)
No evidence
Neuropsychiatric
syndrome
Atypical Bipolar
Anxiety syndrome (20)
Depression, if any
4. Discussion
Superior Parietal lesions (19)
"Hyperactivity syndrome" in AD (16)
(agitation, irritability, aberrant motor behavior, euphoria, and disinhibition)
Inferior PL (22)
Dorsal & Ventral PPC (22)
Goal–directed and reflective attention
Functional Anatomy of the
Parietal Cortex
Inferior Parietal Lobule &
Inferior Parietal Sulcus
episodic retrieval (22) Behrmann M, et al. Parietal Cortex and
Attention. Curr Opin Neurobiol 2004. 14:212–217.
(23) Hutchinson JB, et al. Posterior parietal
cortex and episodic retrieval: Convergent and
divergent effects of attention and memory. Learn
Mem. 2009;16: 343-356
Superior Parietal Lobule
top-down (goal-directed)
spatial shifts in attention &
working memory
Precuneus (Medial PL)
top-down (goal-directed)
non-spatial shifts in attention
Anterior and Inferior Parts of
the Intra-Parietal Sulcus
visual search in the
absence of distractors
(R) Temporo-Parietal
Junction
multisensory attention
to a change in relevant
information
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