Thematic Issues in Modern Alzheimer Research

**3**

**Chapter 1**

*Denis Larrivee*

**1. Introduction**

Introductory Chapter: Beyond Risk

Alleles - Invoking Cognitive Lesions

Improvements in medical care have significantly extended life expectancies, upwardly shifting demographic indicators of the elderly worldwide. Coupled with falling birth rates, however, the number of patients suffering cognitive deficits has also increased. World Health Organization projections, for example, indicate that by 2050, more than 20% will fall in this sector, with considerably higher percentages in developed nations, placing large numbers of individuals at risk [1]. Among the elderly the most prevalent neurodegenerative disease is Alzheimer's disease (AD) with a lifetime risk above 60 of 33% for males and 45% for females. Its growth rate is anticipated to exceed nearly 100% that of current levels in developed nations and more than 300% in Southeast Asian countries [2]. These increases in agerelated diseases, moreover, add to an already significant burden from such prevalent

Symptomatically, prevalent diseases like AD and Korsakoff's syndrome, exhibit profound memory losses. In AD a broad consensus posits that its early symptoms include memory lapses that involve episodic memory, semantic recall, and visual orienting [3]. Among its earliest is an impaired sense of smell, a feature that may relate to evolutionary survival value. With the progression of AD, recent memories

Defined as a process of encoding, storing, and retrieving sensorial or mental information, memory dysfunctions induced by AD may be functionally interpreted as to the manner by which one or more of these phases are affected. Accordingly, the loss of formed memories, or retrograde amnesia, observed in AD patients, can be explained either by a loss of stored memories or an inability to retrieve them. In fact, existing evidence suggests that both phases are affected. Anatomical studies, for example, show a deterioration of thinly myelinated regions like the hippocampus relatively early in the disease progression compared to other regions [4]. Since the hippocampus is a critical center for recently formed memories, this evidence is

consistent with loss of memories, particularly those that have formed first. On the other hand, the disease is known to also specifically affect DMN operation [5], a domain thought to be critical to forming the self-construct. First identified by nuclear imaging studies that showed consistently higher levels of activity during passive task conditions, the DMN was hypothesized to monitor the external environment, body, and even emotions [6]. Task-related increases in activity in regional brain zones coincided with its decreased activity, indicating a reciprocal relation between the two zones related to the performance state of the

mental health diseases as schizophrenia and bipolar disorder.

fade, and there is a proportionately greater retention of older

ones, a characteristic observation termed Ribot's law.

in Top-Down Strategic Analysis
