Preface

It is fair to say that no brain disease occupies more research study today than Alzheimer's disease (AD). Among the many excellent reasons for this circumstance are the bleak prognosis and relentless progression; large cohorts of baby boomers entering an age of greatly increased cognitive risk; spectacular advances in medical care that have prolonged lifespan; and ever-mounting risk with age. Moreover, there is perhaps no dearer feature than self-awareness and the memory of self across time, all of which are taken as the disease marks its course.

Often unattributed in propelling interest in AD is the success of the research enterprise that has advanced the understanding of the brain. From Hodgkin and Huxley's characterization of the action potential less than 70 years ago, neuroscience has identified nearly all brain neurotransmitters, resolved the structure of the major ion channels, and stands poised to decipher the operations of hundreds of thousands of neurons in joint activity. The product of the scientific method of these successes have instilled a confidence that disease causes will ultimately succumb to the persistence of research, and that the accumulation of data from appropriately designed experiments will blossom into therapies that will arrest and perhaps even reverse AD. Such confidence is being tested, however, and may be prolonged by the very strategies that repeat the premises of the past research methods that have so successfully propelled other aspects of neuroscientific research.

Despite the decades of intense research and a rising wave of elderly people, AD remains poorly understood, an enigma amid a tide of neuroscientific advance. Identified more than a century ago, AD is characterized by a constellation of cognitive dysfunctions, the earliest and most prominent being that of impaired recollection. In its many decades of investigation, numerous theories have sought to unify AD's disparate symptoms within a common causal frame. Current readings list some 13 influential hypotheses, the most widely invoked involving the biomarkers, β-amyloid plaques, and neurofibrillary tangles, identified by Alois Alzheimer more than 100 years ago. Other frequently cited causes include dysfunctional energy resourcing, with evidence pointing toward either glycolytic or electron transport stages.

The mystery of AD's origin is compounded by the genetic observations intended to provide improved predictive diagnosis for a swelling demographic sector. Its set of risk alleles is large by non-cognitive disease standards, and new alleles are regularly being added. The current membership is highly diverse, with some alleles affecting the early onset phase, such as the presenilin genes, the late-phase β-amyloid protein, lipidogenesis genes, and even cytoskeletal and immune genes, among a growing set. Most alleles display small phenotypic effects that are non-Mendelian with low penetrance and that are of a quantitative rather than a qualitative nature. Overall, the relatively small effects of individual alleles and the large field of membership obscure rather than enlighten, offering meager

**II**

**Chapter 7 105**

An Examination of Factors Influencing Equitable Access to Dementia Care and Support Programs among Migrants and Refugees Living with Dementia:

*by Winnie Sun, Srija Biswas, Michelle Dacanay and Ping Zou*

A Literature Review

insight into the causal factors inducing AD's relentless progression. Indeed, genetic observations suggest that affected gene products are neither individually crucial nor functionally irreplaceable components of cognitive processes. They suggest instead that while exerting a limited influence on individual constituents, AD's chief effects may instead target systemic and even global events, where cognition is the product of more flexible physical associations, and where the dysfunction of individual components does little to diminish functional adequacy.

*What the inconclusive results thus appear to do is call into question an understanding of cognition that views it from the bottom up—the study of which is eminently suited by the scientific method—and that dispenses with a philosophy of biology concerned with how organismal properties operate, for which cognition is the medium.*

Accordingly, the chapters of this text intend to give evidence that "bottom-up" approaches—nearly exclusively pursued in AD research—yield limited insight into causal etiology and so implicate the need to undertake fundamentally different strategic avenues. Chapter 2, for example, is illustrative for showing how singular theories like that of impaired glycolysis face numerous findings that conflict with outcomes predicted by theory, as does Chapter 3 on mitochondrial dysfunction. Chapter 4 proposes, in consequence, that protective measures against cellular lysis may offer a general though non-specific way forward to arresting degeneration. The question of whether the findings obtained from these studies are etiological, or merely epiphenomenal, accordingly remain unaddressed. Indeed, a number of studies point to impairments of global phenomena, like the self-construct, in AD. Recent findings, for example, have demonstrated that functional connectivities between key nuclei within the default mode network, a domain linked to self-recognition, are weakened. Relating these specific global effects to the sort of generalized disarray that is seen at lower levels of function suggests that old strategies used for exploring the disease would be better directed in new strategical ventures concerned with global cognition, a point emphasized in the first chapter for looking beyond reductive approaches alone.

A significant issue also raised by the present lack of insight into etiology is that of determining patient therapy for what is manifestly a debilitating and personally tragic circumstance. Extant findings from a large body of research suggest that treatment options relying on the correction of single molecular entities are likely to offer little that will be therapeutically advantageous or substantially mitigate the advance of the disease. In the absence of such singular pharmacological options, they suggest that therapies ordered to global aspects of cognition are likely to be more fruitful in slowing symptomatic progression. In this vein, widely adopted healthcare management models, discussed in Chapters 5 and 6 that emphasize the person as a whole, are more likely to improve global self-representation through cognitive integration. As pointed out in Chapter 7 on the current level of cultural diversity within immigrant populations, these efforts will need to be expanded to enable the access of these groups to such care, particularly in cases where cultural constraints impede involvement.

**V**

It is hoped that this text will inspire debate on new "top-down" strategical alternatives to the current preeminent "bottom-up" models and underscore the humanitar-

> **Denis Larrivee** Visiting Scholar,

> > USA

Loyola University Chicago,

University of Navarra Medical School,

Mind and Brain Group

Pamplona, Spain

ian issue that is at the heart of care for the AD patient.

It is hoped that this text will inspire debate on new "top-down" strategical alternatives to the current preeminent "bottom-up" models and underscore the humanitarian issue that is at the heart of care for the AD patient.

**Denis Larrivee**

Visiting Scholar, Loyola University Chicago, USA

Mind and Brain Group University of Navarra Medical School, Pamplona, Spain

**IV**

constraints impede involvement.

alone.

adequacy.

*medium.*

insight into the causal factors inducing AD's relentless progression. Indeed, genetic observations suggest that affected gene products are neither individually crucial nor functionally irreplaceable components of cognitive processes. They suggest instead that while exerting a limited influence on individual constituents, AD's chief effects may instead target systemic and even global events, where cognition is the product of more flexible physical associations, and where the dysfunction of individual components does little to diminish functional

*What the inconclusive results thus appear to do is call into question an understanding of cognition that views it from the bottom up—the study of which is eminently suited by the scientific method—and that dispenses with a philosophy of biology concerned with how organismal properties operate, for which cognition is the* 

Accordingly, the chapters of this text intend to give evidence that "bottom-up" approaches—nearly exclusively pursued in AD research—yield limited insight into causal etiology and so implicate the need to undertake fundamentally different strategic avenues. Chapter 2, for example, is illustrative for showing how singular theories like that of impaired glycolysis face numerous findings that conflict with outcomes predicted by theory, as does Chapter 3 on mitochondrial dysfunction. Chapter 4 proposes, in consequence, that protective measures against cellular lysis may offer a general though non-specific way forward to arresting degeneration. The question of whether the findings obtained from these studies are etiological, or merely epiphenomenal, accordingly remain unaddressed. Indeed, a number of studies point to impairments of global phenomena, like the self-construct, in AD. Recent findings, for example, have demonstrated that functional connectivities between key nuclei within the default mode network, a domain linked to self-recognition, are weakened. Relating these specific global effects to the sort of generalized disarray that is seen at lower levels of function suggests that old strategies used for exploring the disease would be better directed in new strategical ventures concerned with global cognition, a point emphasized in the first chapter for looking beyond reductive approaches

A significant issue also raised by the present lack of insight into etiology is that of determining patient therapy for what is manifestly a debilitating and personally tragic circumstance. Extant findings from a large body of research suggest that treatment options relying on the correction of single molecular entities are likely to offer little that will be therapeutically advantageous or substantially mitigate the advance of the disease. In the absence of such singular pharmacological options, they suggest that therapies ordered to global aspects of cognition are likely to be more fruitful in slowing symptomatic progression. In this vein, widely adopted healthcare management models, discussed in Chapters 5 and 6 that emphasize the person as a whole, are more likely to improve global self-representation through cognitive integration. As pointed out in Chapter 7 on the current level of cultural diversity within immigrant populations, these efforts will need to be expanded to enable the access of these groups to such care, particularly in cases where cultural

**1**

Section 1

Thematic Issues in Modern

Alzheimer Research

Section 1
