**Changes in Visual Cortex in Healthy Aging and Dementia**

Alyssa A. Brewer and Brian Barton

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64562

#### **Abstract**

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2013.4544

272 Update on Dementia

s13195-015-0105-6

This chapter reviews the differences in specific structural and functional characteris‐ tics of human visual cortex among young adults, healthy aging adults, and patients with dementia, with a primary focus on those with Alzheimer's disease (AD). Such visual cortex changes have been shown to underlie many of the behavioral deficits that develop in healthy aging and AD. Measurements of disordered visual cortex in dementia patients may be possible early in the course of neurodegeneration and thus may be useful for improving early diagnosis of these devastating diseases.

**Keywords:** visual cortex, visual field mapping, dementia, healthy aging, functional neuroimaging

### **1. Introduction**

#### **1.1. Overview of visual cortex characteristics**

Human visual cortex can be partitioned into distinct topographical representations of visual space called visual field maps (VFMs), each of which subserves separate perceptual functions spanning the hierarchical stages of visual processing [1–3]. The organization of a VFM fol‐ lows the organization of the retina; hence, retinotopic VFMs are cortical regions in which nearby neurons analyze the properties of nearby points of an image on the retina, and thus of visual space. This VFM organization is one of the more important, larger-scale, organizing princi‐ ples of visual cortex. Such topographic organization is thought to allow for efficient connectiv‐ ity among neurons that represent nearby aspects of visual space, likely necessary for such processes as lateral inhibition and to compactly organize neural signals ranging from the molecular level to that of the cerebral hemisphere [4–7]. In addition, measurements of the characteristics of these VFMs, together with an understanding of the stimulus selectivity of the

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

neurons within them, is the foundation for understanding the specific visual computations carried out in particular cortical regions. Not only are such *in vivo* measurements of VFMs essential for the study of visual processing in healthy subjects, but they also are very effective for tracking changes in visual cortex in response to changes in visual inputs such as those that arise from retinal or cortical damage [8–12].

Although historically the organization and function of visual cortex have been primarily well characterized in healthy young adults or young patient populations [1–3, 8, 12–16], many behavioral studies [17–38] and more recent neuroimaging studies [36, 37, 39–55] are suggesting that several changes occur within visual pathways during what is considered otherwise healthy aging. These studies specifically describe retinal and cortical changes, rather than optical changes in the eye, that primarily contribute to the decreases in visual acuity and related issues that have been measured in healthy aging subjects [19, 33, 46, 50, 54]. These healthy aging changes are also now starting to be compared to pathophysiological changes in visual cortex in age-related disorders like dementia, including diseases such as Alzheimer's disease (AD), posterior cortical atrophy (PCA), and dementia with Lewy bodies (DLB), in the hopes of both improving our understanding of these diseases and aiding improvements in potential therapies [37, 56].

Visual deficits are reported surprisingly often as one of the first symptoms of AD, the most common form of dementia. These deficits can include problems with visual-spatial attention, visual-spatial tasks, and visual-processing speed [37, 40, 47, 57–75]. A subset of dementia patients presents with prominent visual symptoms such as problems with visual field defects, contrast sensitivity, color discrimination, and feature recognition of complex objects, but little initial decline in memory. These patients have increased neuropathology in visual cortex, as compared to typical AD patients [76–84]. Dementia with these characteristics was initially often referred to as visual variant AD, but it is now usually termed PCA. DLB, the second most common type of dementia, also often presents with visual complaints [85]. Like in AD and PCA, the central features of DLB include progressive cognitive decline, typically with impair‐ ments in memory, visual-spatial abilities, and attention. However, unlike AD and PCA, one of the earliest visual symptoms in this disease is commonly visual hallucination [86].

Early detection and accurate diagnosis are keys in the hope for a cure for such dementias, as early, precise diagnosis would allow for more timely initiation of treatments. As visual symptoms can occur early in these diseases, studies are beginning to demonstrate that measurements of related changes in visual cortex in these patients could aid early detection of neurodegeneration. The highly structured representations within VFMs afford a funda‐ mental measurement that might be used to detect subtle effects of neurodegeneration early in the disease process. Clear measures of the progression of the pathology within visual cortex might also help to target drug research for therapeutic interventions, especially by differenti‐ ating among different types of dementia [62]. The information reviewed in this chapter will serve as a foundation for subsequent use of this knowledge in our evaluation, interpreta‐ tion, and treatment of these diseases. As little has been studied regarding VFMs in patients with PCA or DLB, this chapter will focus on measurements from patients with AD.

#### **1.2. Review methodology**

neurons within them, is the foundation for understanding the specific visual computations carried out in particular cortical regions. Not only are such *in vivo* measurements of VFMs essential for the study of visual processing in healthy subjects, but they also are very effective for tracking changes in visual cortex in response to changes in visual inputs such as those that

Although historically the organization and function of visual cortex have been primarily well characterized in healthy young adults or young patient populations [1–3, 8, 12–16], many behavioral studies [17–38] and more recent neuroimaging studies [36, 37, 39–55] are suggesting that several changes occur within visual pathways during what is considered otherwise healthy aging. These studies specifically describe retinal and cortical changes, rather than optical changes in the eye, that primarily contribute to the decreases in visual acuity and related issues that have been measured in healthy aging subjects [19, 33, 46, 50, 54]. These healthy aging changes are also now starting to be compared to pathophysiological changes in visual cortex in age-related disorders like dementia, including diseases such as Alzheimer's disease (AD), posterior cortical atrophy (PCA), and dementia with Lewy bodies (DLB), in the hopes of both improving our understanding of these diseases and aiding improvements in potential

Visual deficits are reported surprisingly often as one of the first symptoms of AD, the most common form of dementia. These deficits can include problems with visual-spatial attention, visual-spatial tasks, and visual-processing speed [37, 40, 47, 57–75]. A subset of dementia patients presents with prominent visual symptoms such as problems with visual field defects, contrast sensitivity, color discrimination, and feature recognition of complex objects, but little initial decline in memory. These patients have increased neuropathology in visual cortex, as compared to typical AD patients [76–84]. Dementia with these characteristics was initially often referred to as visual variant AD, but it is now usually termed PCA. DLB, the second most common type of dementia, also often presents with visual complaints [85]. Like in AD and PCA, the central features of DLB include progressive cognitive decline, typically with impair‐ ments in memory, visual-spatial abilities, and attention. However, unlike AD and PCA, one

of the earliest visual symptoms in this disease is commonly visual hallucination [86].

with PCA or DLB, this chapter will focus on measurements from patients with AD.

Early detection and accurate diagnosis are keys in the hope for a cure for such dementias, as early, precise diagnosis would allow for more timely initiation of treatments. As visual symptoms can occur early in these diseases, studies are beginning to demonstrate that measurements of related changes in visual cortex in these patients could aid early detection of neurodegeneration. The highly structured representations within VFMs afford a funda‐ mental measurement that might be used to detect subtle effects of neurodegeneration early in the disease process. Clear measures of the progression of the pathology within visual cortex might also help to target drug research for therapeutic interventions, especially by differenti‐ ating among different types of dementia [62]. The information reviewed in this chapter will serve as a foundation for subsequent use of this knowledge in our evaluation, interpreta‐ tion, and treatment of these diseases. As little has been studied regarding VFMs in patients

arise from retinal or cortical damage [8–12].

therapies [37, 56].

274 Update on Dementia

We performed a systematic review to investigate whether there are changes in early VFMs V1, V2, V3, and hV4 characteristics to healthy aging subjects and patients with AD or related dementias that can be measured using functional magnetic resonance imaging (fMRI). In order to include as many relevant citations as possible, we searched a comprehensive range of scientific databases including CogPrints, FreeFullPDF, Google Scholar, IngentaConnect, JSTOR, Mendeley, Microsoft Academic Search, PubMed, PubPsych, ResearchGate, and Web of Science. In addition, the Google search engine was used to find institutional, professional, and personal webpages hosting potentially relevant PDFs or citation links. Searches were performed from November 2015, to May 2016. Search queries included the following terms in various combinations: visual cortex, visual field map, visual area, primary visual cortex, V1, V2, V3, hV4, occipital cortex, visual changes, fMRI, pRF modeling/modeling, neuroimaging, aging, healthy aging, human, dementia, neurodegeneration, mild cognitive impairment, Alzheimer's disease, dementia with Lewy bodies, Lewy body dementia, and posterior cortical atrophy. Related citation links available for the various database searches were routinely evaluated to investigate additional potential citations of interest. All potential study designs were included, and potentially relevant citations spanned the dates 1925–2016; note that visual field mapping with fMRI was relatively recently introduction in 1994 [87].

Ultimately, 317 potentially relevant citations were downloaded to EndNote for further evaluation. The full papers of these citations were assessed and selected to only include studies that directly related to comparing fMRI measures of visual cortex or visual field maps in healthy young adults (aged 18–40 years) to changes in visual cortex or visual field maps in healthy aging subjects with no known age-related diseases or specific, clinically recognized deficits in vision (aged 55–80 years) and/or to patients with mild-to-moderate AD with no known visual deficits unrelated to dementia (aged 55–80 years). No studies of VFM changes in DLB or PCA were found during the initial database searches, which was not unexpected given the very recent emergence of interest in visual field mapping in dementia. Additional studies of visual field mapping methodology and of visual symptoms associated with healthy aging, AD, DLB, and PCA were also retained for methods discussion and hypothesis devel‐ opment, respectively. Studies were further evaluated for quality and were excluded if they lacked statistical analysis or if they did not use accurate cortical field mapping techniques with individual subject analysis (for further discussion of these criteria, see [1, 3, 88]).

Of the 317 downloaded studies, 165 papers were directly relevant to this review, of which 88 focused on visual changes in aging or dementia. Of these, 24 studies measured changes specifically in visual cortex related to aging and/or dementia, and three studies explicitly investigated VFM changes in aging and/or dementia, as appropriate with respect to the inclusion and exclusion criteria [36, 37, 39]. Here, we provide both a narrative discussion of all 165 sources as well as graphical examples drawn from the three key visual field mapping studies. We discuss what is known regarding changes in early visual cortex during healthy aging and AD, how these findings relate to visual symptoms in these conditions, and what remains to be studied, and we recommend directions for future research.
