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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