**Normal Aging and Dementia**

Michał Prendecki, Jolanta Florczak-Wyspianska, Marta Kowalska, Margarita Lianeri, Wojciech Kozubski and Jolanta Dorszewska

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64203

#### **Abstract**

Normal aging begins after 60 years of age. According to Harman, the accumulation of free radicals, which results from weakening of repair and protective mechanisms, takes place in the aging brain. It is believed that especially in the population of the most elderly there is increased incidence of both dementia and depression. The causes of these central nervous system disorders in the aging human body are changes at the molecular level, such as changes in the biochemical parameters, the accumulation of mutations in nuclear and mitochondrial DNA, and epigenetic changes. Biomarkers associated with aging of the brain include accumulated deposits of β-amyloid (Aβ), disturbed cholesterol homeostasis, altered neuroimaging parameters, and impaired glucose metabolism. Genetic factors are also responsible for normal aging, for example, *SIRT1, AKT1*, and *CDKN1A*, and among them the longevity genes, such as *FOXO3A* and *CETP*. Dementia as well as cognitive decline may be modified by poly-T variants of *TOMM40* and *APOE* alleles via influencing the level of apolipoprotein E (apoE) in the brain and in the plasma as well as by its ability of Aβ clearance.

Identifying the molecular factors associated with aging and dementia may help introduce new approaches to preventing geriatric disorders, including depression and dementia.

**Keywords:** molecular factors, dementia, normal aging

#### **1. Introduction**

Currently, average life expectancy in the world is over 60 years. The world's longest life expectancy is in Japan, at 82.2 years, and in Australia, at 80.6 years. In Europe, the longest-

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lived people are the French, at 80.6 years, the Swedes, at 80.6 years, the Italians, at 79.9 years, the Greeks, at 79.3 years, the Dutch, at 79.1 years, and the Germans, at 78.9 years. It is predicted that in Europe from 2005 to 2050, the number of people following into their 80th year of life will increase by 43 million [1].

In psychological studies on the elderly, three subperiods were stratified among people over 60 years old; these included *young olds* (65–75 years of age), *old olds* (75–85 years old), and *eldest olds* (over 85 years of age). Deterioration of cognitive functions was visible in the *eldest olds* age group, while asymptomatic structural changes in the brain, such as cortical atrophy, poli- and leukoaraiosis (deterioration of white matter, present in 8–90% of the elderly with no signs of dementia), or decreased glucose metabolism and deteriorated subcortical and cortical flow, could be detected by neuroimaging even among the *young olds* [2].

Progressive aging of the population is one of the factors determining the increasingly frequent occurrence of cognitive impairment and dementia syndromes. Dementia, due to its prevalence in the population (it occurs in approximately 10% of those 65 years of age and in approximately 30–40% of those 90 years of age), requires great concern and clinical care. It is estimated that by 2040, the number of elderly people with dementia in the world will exceed 80 million [3].

According to the classification of mental disorders in the American Psychiatric Association's DSM – IV (Diagnostic and Statistical Manual of Mental Disorders) [4], there is no isolated, separate diagnostic category for "dementia," but the criteria for this diagnosis are contained in the various types of dementia, for example, Alzheimer's disease (AD), vascular dementia (VD), or in other diseases. According to these criteria, a diagnosis of dementia is necessary to determine the presence of multiple cognitive deficits that cause significant disturbances in the functioning of social exclusion and mental illness (depression) and delirium.

*Dementia* is a progressive impairment of the functional status and significantly reduces the quality of life of older people in all its dimensions, since physical disability and the loss of sphincter control coexist along with dementia. The most common cause of dementia in the oldest patients is the degenerative process that is underway in the brain in the course of AD. In old age, an important process associated with the degeneration of neurons in AD is cerebral arteriosclerosis. Dementia, with dying neurons, is caused by both pathologies. A high per‐ centage of the causes of dementia in the elderly may develop depression. In these patients, the following is observed especially often: loss of interest, sleep disturbances, psychomotor disturbances, and problems with concentration. In turn, the use of multiple drugs in dementia complicates the diagnosis of depression [4].

*Depression* is defined as an emotional distress syndrome (states of depressed mood, depres‐ sion), which is often co-morbid with somatic diseases and/or with intensifying their symptoms. Depression is a common and serious problem among the elderly and increases mortality. Approximately 15% of people over the age of 65 have symptoms of depression, which impede daily functioning [2, 4].

It is believed that the functional and cognition changes observed in older persons are associated with disturbances at the molecular level in the aging body. Molecular changes in the aging process may relate to genomic instability as a result of accumulation of mutations, telomere attrition and epigenetic alterations, and alteration in the level of brain biomarkers [2].

To select significant studies for this review, the authors conducted multiple searches through public databases, including PubMed and Scopus, by using the following search strategy: ("normal aging" or "aging") and ("dementia" or "cognitive decline") and ("biomarker" or "SNP" or "genetic polymorphism" or "mutation"). The last search was performed in February 2016. A subsequent data mining through review articles and references facilitated finding additional eligible studies.
