Diagnosis of Posterior Cortical Atrophy Delayed by Coexisting Fuchs’ Endothelial Corneal Dystrophy

Abstract

Posterior cortical atrophy (PCA), also known as the visual variant of Alzheimer’s Disease, is a rare neurodegenerative disorder that affects the visuospatial systems in its initial stages. Due to the rarity of this condition and the presence of relatively preserved memory during its early stages compared to other dementias, its accurate diagnosis can be delayed. When accompanied by a comorbid visual disorder, the diagnostic process becomes even more challenging. This study describes the disease course of a patient whose diagnosis of Fuchs’ Endothelial Corneal Dystrophy served to delay an additional diagnosis of PCA, illustrating the necessity of careful scrutiny of symptom presentation and especially its course.

Introduction

Posterior cortical atrophy (PCA) is commonly conceptualized as the visual variant of Alzheimer’s disease (AD). Benson et al ¹ recognized PCA as a syndrome in their description of a small group of patients who were distinct in presentation compared to others evaluated for dementia. They described patients who retained normal visual acuity and visual fields but displayed “disabling visual problems” including agnosia, alexia, anomia, Gerstmann’s syndrome (right/left confusion, finger agnosia, agraphia, and acalculia), and Balint’s syndrome (visuomotor problems, sticky fixation, and simultagnosia). ¹ In contrast to classic AD, the initial symptom profile of PCA is characterized by slowly progressive deterioration of visuospatial skills with relative preservation of verbal and memory abilities. ² The age of onset is typically in the fifth or sixth decade, making this an “early-onset” dementia. ^3,4 Although the progressive neurodegeneration that underlies PCA is attributable to AD in most patients, alternate underlying causes, including dementia with Lewy bodies, corticobasal degeneration, and prion disease, have also been identified. In addition, not all patients with PCA necessarily have atrophy on initial clinical imaging. ³ This heterogeneity has restricted generalizability in diagnosis and terminology, especially in initial and late stages, making this disease difficult to diagnose. ^5,6

Fuchs’ dystrophy, or Fuchs’ endothelial corneal dystrophy (FECD), is characterized by progressive loss of corneal endothelial cells, thickening of Descement’s membrane, and deposition of extracellular matrix in the form of guttae, resulting in the swelling of the cornea and subsequent vision loss. ⁷ We present a case of a woman who was diagnosed with and treated for FECD but subsequently demonstrated the progressive symptoms of PCA. The PCA diagnosis was confounded for years by her documented history of FECD.

Case Report

A 59-year-old, left-handed, English-speaking woman with 16 years of education, presented with a 4- to 5-year progressive decline in visuospatial skills, short-term memory, and word-finding ability, as reported by her and her husband. Two years prior to her neurology appointment, the patient was diagnosed with FECD and received endothelial corneal transplants and posterior chamber implants. Her visual acuity improved after the transplants, with her corrected vision rated as 20/50 in the right eye and 20/40 in the left eye. Multiple health care providers attributed the patient’s visuoperceptual complaints to FECD, but despite the postsurgical improvement in visual acuity, the patient continued to experience significant problems in this area.

The patient and her husband provided several examples of her visuoperceptual difficulties. For example, when exiting a room she had to search for the door so that she would not walk into a wall. She would often trip on the stairs, making her susceptible to falls. She reported difficulty understanding what she read, and that she could not read cursive handwriting any longer, including her own. Her handwriting had also changed in the past few years. She also reported disorientation with regard to the driver and passenger sides of her car, signs of dressing apraxia (eg, frequently put her shirt on backwards), and inability to do mental math. She also had difficulties picking out a kitchen utensil from an array of such items in a drawer, locating a single item on a shelf in a grocery store, completing a child’s jigsaw puzzle, recognizing bills and coins, and recognizing geese in a field. Her husband described her tendency to turn into a curb by mistake when attempting to turn into a driveway when riding a bike. These visuoperceptual difficulties interfered with the patient’s ability to perform her duties in her work as a nurse, resulting in her eventual resignation. She reportedly maintained independence in activities of daily living (ADLs) such as medication management, cooking familiar meals, driving familiar routes, and shopping, but reported that all ADLs required significantly more time to complete.

Additional health history includes mild concussion (no loss of consciousness) 10 years prior to evaluation and FECD (as discussed earlier). Medications included ibandronate sodium and loteprednol etabonate ophthalmic suspension. She denied alcohol, drug, and tobacco use. Family medical history includes moderate dementia in her 85-year-old father (type unknown) and bipolar disorder in her brother. Magnetic resonance imaging of the brain revealed parietooccipital atrophy, more prominent on the right (Figures 1 and 2).

Figure 1.

Patient magnetic resonance imaging (MRI)—coronal T1.

Figure 2.

Patient magnetic resonance imaging (MRI)—axial T1.

The patient was referred for neuropsychological evaluation due to the cognitive difficulties that remained after successful treatment of FECD.

The patient’s general physical and neurological examinations were normal with the exception of visual field testing. The patient seemed to be quite a bit more hesitant when counting fingers in the left hemifield.

The results of the neuropsychological evaluation are summarized in Table 1. The patient was alert, responsive, and fully oriented on the day of the evaluation. Receptive language and speech output were intact. She reported having “low vision.” Gait and posture were unremarkable. She did not display right/left confusion during neuropsychological testing.

Table 1.

Patient’s Neuropsychological Performances by Domain.

Domain	Subdomain	Measure	Standard Score (Mean = 100; Standard Deviation = 15)	Percentile
General intelligence and achievement	Academic	WRAT-IV word reading	113	81
	Overall intelligence	WAIS-III full-scale IQ	81	10
	Verbal intelligence	WAIS-III verbal IQ	104	62
	Performance intelligence	WAIS-III performance IQ	58	<1
Learning and memory	Visual memory	BVMT-R total	62	1
		BVMT-R long-delay recall	61	<1
	Verbal memory	CVLT-II trials 1-5 total	81	10
		CVLT-II trial B	93	32
		CVLT-II short-delay recall	78	7
		CVLT-II long-delay recall	78	7
		CVLT-II discriminability	93	32
Attention	Working memory	WAIS-III working memory	88	21
		WMS-III working memorya	74	4
	Visual attention	Trail making test A	<45	<1
Executive functioning	Mental flexibility	Trail making test B	<45	<1
	Novel problem solving	WCST-64 total error	71	3
		WCST-64 perseverative responses	72	3
		WCST-64 perseverative errors	70	2
		WCST-64 categories completed	NA	11–16
Processing speed	Cognitive speed	WAIS-III processing speed	66	1
Language	General verbal skills	WAIS-III verbal comprehension	112	79
	Expressive	Semantic verbal fluency	81	10
		Phonemic verbal fluency	126	96
		Boston naming test	73	4
Visuospatial functioning	Perceptual skills	WAIS-III perceptual organizational	62	<1
		Benton facial recognition test	<62	<1
		Judgment of line orientation	74	4
	Visuospatial construction	DRS-2 construction	65	1
		Rey-Osterrieth complex figure copy	2.5/36 (raw)	<1
Affect	Mood	CES-D	15/60 (raw)	NA

Abbreviations: WRAT-IV, Wide Range Achievement Test-IV; WAIS-III, Wechsler Adult Intelligence Scale III; WMS-III, Wechsler Memory Scale-III; BVMT-R, Brief Visuospatial Memory Test-Revised; CVLT-II, California Verbal Learning Test-II; WCST, Wisconsin Card Sorting Test; DRS-2, Dementia Rating Scale-2; CES-D, Center for Epidemiological Studies-Depression scale; NA, not applicable.

^aWMS-III Working Memory Index includes a subtest requiring visual working memory.

The patient performed within normal limits on measures of orientation, phonemic and semantic verbal fluency, verbal intelligence (IQ), auditory working memory, and some aspects of auditory memory.

However, impairment was evident on tests within the domain of visuospatial and perceptual abilities, including visual memory. These deficits ranged from mild to severe. The patient’s difficulties included mild dysgraphia and dysnomia. Although she reported occasional word-finding difficulties, her visual naming of 2-dimensional objects was notably impaired on formal testing. This deficit was attributable to more visual perceptual deficit than language dysfunction. Borderline impairment on a test of executive functioning was also likely due to the visual demands of the test. Verbal memory was low average to borderline impaired, but comparatively intact, without a pattern of rapid forgetting. Consistent with other case reports of PCA, while the patient’s Full-Scale IQ (FSIQ) was in the low average range (Wechsler Adult Intelligence Scale III [WAIS-III] FSIQ = 81), there was a significant difference between her Verbal IQ (WAIS-III VIQ = 104; average range) and Performance IQ (WAIS-III PIQ = 58; moderately impaired range). This is a 3 standard deviation VIQ–PIQ difference.

On a self-report inventory of depression, the patient scored within normal limits. She did endorse increased irritability.

In summary, the patient’s cognitive data were indicative of significant impairment, particularly in the domain of visuospatial ability. Given her history of progressive cognitive decline during the past 4 to 5 years and evidence of atrophy in the parietooccipital junction, her results were considered consistent with PCA. Her history and test profile suggested she was in the mild–moderate stage of the disease.

Discussion

Posterior cortical atrophy can be a difficult diagnosis to make in the dementia clinic, given comparatively preserved memory. When confounded by a documented history of a vision disorder (eg, FECD), differential diagnosis is further complicated. This case highlights the importance of thorough investigation in clinical interview, especially in tracking the timeline of symptom progression. Many patients present with multiple symptoms that are best explained by a single diagnostic entity, and the law of parsimony is usually a good one. However, accurate diagnosis in this case was delayed by symptom presentation being attributed to the history of FECD. A multidisciplinary approach to the case helped elucidate the additional PCA diagnosis.