Memory dysfunction is one of the most notable symptoms of an aging brain, especially after 50 years of age. As a result of memory failure, all aspects of life are affected, including employment, independence, socialization, relationships, and general productivity.

Research indicates that neural mismatches begin to appear in individuals as young as 40 years of age, resulting in increased vulnerability to distraction [8]. By 65 years of age, one-fourth of the population struggles with a failing memory and a range of mild cognitive problems. Most notable is the "senior moment" of forgetting a person's name; this is known as paraphasia. As cognitive and biologic changes take place, aging persons are forced to learn compensatory skills to continue functioning as best they can for as long as possible.

Normal signs of aging can be distinguished from the more advanced signs of mild cognitive impairment (MCI), dementia, and AD. Normal aging may include the following behavioral changes or losses:

Forgetting names of people one rarely sees, such as a former neighbor

Forgetting parts of an experience, such as parts of a vacation trip with a friend

Occasionally misplacing an item, such as car keys or a cell phone

Extreme mood changes related to a relevant or appropriate cause, such as recalling the death of a spouse

Temporarily being unable to recall a specific fact while telling a story or a past event or experience

Change and loss of interest in various age-related activities

Nonetheless, the normal brain is an aging brain, and steps should be taken to maintain or improve everyday functioning. The following steps can be taken to improve the brain's functioning throughout one's life [11,12]:

Stay physically active.

Stop smoking or never start.

Avoid excess alcohol.

Engage in cognitive training.

Maintain social networks.

Protect the brain from toxic exposure and closed head injury.

Eat a nutritious and balanced diet.

Ingest the daily required minimum of vitamins, minerals, omega fatty acids, water, fruits, and vegetables.

Sleep six to eight hours each night.

Engage in an array of social, intellectual, spiritual, and physical activities.

Maintain a positive attitude about life events and circumstances.

Engage in an active life of service to others.

Control stress and learn to cope well with daily stressful events.

Keep personal belongings and things well organized.

Focus on the goals of what one desires to pursue and achieve.

Treat any psychologic problem early, such as attention deficit hyperactivity disorder (ADHD), depression, and substance abuse.

Although the brain is always changing, individuals have some control over the rate and nature of the changes taking place from childhood onward. The degree of control depends on an understanding of the brain structures and functions. Understanding the brain's changing capabilities can yield a corresponding improvement in a person's productivity, learning, and creativity. For example, researchers have found that microscopic injury-based changes in the blood vessels in the brain (referred to as microinfarcts) may lead to brain functioning problems in later life [13]. The control of blood pressure minimizes vascular microinfarcts and lowers the risk of dementia onset.

Social integration has been found to delay the decline of memory among Americans 50 years of age and older. Those adults with the highest level of social integration over a six-year period experienced a slower rate of cognitive decline than their less social peers [14].

Through the process of aging and traumatic events, mild signs of neurologic dysfunction may begin to show. MCI is a spectrum of mild but persistent memory loss that lies between normal age-related memory loss and diagnosed dementia and AD. The memory deficits are beyond those expected for the person's age, and the individual persistently forgets meaningful information that he or she wants to remember. However, other cognitive functions may be normal, there is little loss of ability to work or function in typical daily activities, and there are no other clinical signs of dementia. MCI affects 15% to 20% of the aging population [9]. The presence of MCI may be the factor that influences the course of dementia toward AD. Among those with MCI, approximately 15% develop dementia after two years and approximately 32% develop AD within five years [9]. The signs of MCI go beyond those described as normal signs of aging. This level of impairment may last for a short time or for years.

While progressive, the first step on the pathway to dementia is not always memory loss. Impairments of other cognitive skills, such as map reading, working jigsaw puzzles, and other visuospatial skills mediated in the right hemisphere of the brain, may be early signs of cognitive impairment [14]. Researchers have found that financial decision making and arithmetic functions decline one to three years earlier than memory functions [20]. Other signs were related to executive and attentional skill decline. Such research findings are important to the process of early detection of MCI, which can lead to earlier initiation of treatment and preventative measures for more advanced cognitive impairment. Early intervention among high-risk populations is an urgent area of research and experimental studies.

Dementia is a progressive and profound disruption in brain function and intellectual capacity. The primary signs include problems with memory, language, spatial-temporal reasoning, judgment, emotionality, thought disorder, and personality. Dementia is a subtle progressive loss of cognitive functioning, with memory loss as its hallmark impairment, particularly loss of short-term memory. The ability to concentrate, make judgments, problem solve, and engage in abstract thought processes is also impaired. Personality and mood changes distinct from previous experiences are likely to develop, such as depression, apathy, elation, and anger. Impulse control becomes a major impairment with associated difficulties in social and physical relationships. Finally, grandiose and persecutory delusions are fairly common, especially in the more advanced stages of dementia [21]. It is possible for a young person to have dementia, but this is usually a result of a neurologic traumatic event or major illness with neurologic corollaries.

While 60% to 80% of cases of advancing dementia are categorized as the Alzheimer type, other disorders may fall within the broader classification of dementia [9]. These include but are not limited to [9,23]:

Vascular dementia: Rapid onset secondary to multi-infarct events

Huntington disease with dementia: Progressive inherited breakdown of the central nervous system in early adulthood affecting movement, cognition, and emotions

Human immunodeficiency virus (HIV) with dementia: Slow-onset dementia related to the progressive HIV infectious process affecting speed of motion, memory coordination, socialization, affect, and thought processes

Parkinson disease with dementia: Dementia beginning about one year after the diagnosis of Parkinson disease has been affirmed

Dementia with Lewy bodies (DLB): Characterized by visual hallucinations, an impairment of visuospatial/constructional functioning with a rapid onset and rapid decline, and often Parkinsonian motor dyscontrol and cognitive loss

Spatio-temporal lobar degeneration (FTLD): Generally related to a traumatic impact to the frontal lobe, as in a motor vehicle accident, fall, or a career in boxing or similar sports with a repetitive cranial impact

Mixed dementia: Characterized by the hallmark abnormalities of more than one type of dementia—most commonly AD combined with vascular dementia

Creutzfeldt-Jakob disease: Degenerative neurologic disorder associated with early development of dementia and the presence of prions, a type of infectious protein

There are also many reversible conditions that can mimic dementia [9]. For this reason, dementias must be fully assessed and diagnostically clarified [24]. Specific disorders known to cause pseudodementias include but are not limited to:

Reactions to medications

Metabolic disturbances

Vision and hearing deficits

Nutritional deficiencies

Endocrine abnormalities

Infections

Subdural hematoma

Brain tumors and hydrocephalus

Atherosclerosis

An annual screening system called the Early Detection and Screen for Dementia was developed by the National Task Group on Intellectual Disabilities and Dementia Practices for the early detection of dementia (abbreviated NTG-EDSD) [25]. The NTG-EDSD is designed to be incorporated into an annual physical examination or incorporated into wellness screening programs. The results of a screening assessment indicates if a referral for neuropsychologic assessment or further evaluation is needed. A baseline should be established at 65 or 70 years of age to ensure that a reasonably accurate profile is established and false positives minimized. The NTG-EDSD is available online at https://www.the-ntg.org/ntg-edsd[25].

Many people with dementia will not progress to AD. However, of all those with dementia, 60% to 80% develop the pattern of AD [9]. AD is more prevalent in women than men. Of the 6.7 million people 65 years of age and older with AD in the United States, 4.1 million are women and 2.6 million are men. Among people 65 years of age and older, 12% of women have AD and other dementias, compared with 9% of men [9]. The number of new cases of AD increases proportional to the increase of older adult populations. The annual incidence among those between 65 and 74 years of age is 0.4%. Between 75 and 84 years of age, this increases to 3.2%; it is 7.6% in those 85 years of age and older [9]. The prevalence of AD is expected to grow from 6.1 million in 2020 to nearly 14 million in 2060, largely due to the increase in the older adult population [9].

As the progression of AD is rapid, it is important to consider if any family member has any "unfinished business" that should be constructively addressed early in the disease process. Devoting time to being a care provider is reasonable when there is a clear sign that long overdue forgiveness, past hurts, or neurotic attachments have been resolved. If there are issues that are unaddressed, this may result in further injury in addition to historical hurts and dysfunctional relationships. While the care level may look reasonable, it may really be subtly destructive. Neurotic attachments are all too common and create a host of care problems.

Lewy bodies, named for F.H. Lewy, who first described the condition in 1914, result from a buildup of alpha-synuclein protein in neurons in the brain [32]. This is distinct from the beta-amyloid protein fragments (plaques) and twisted strands of tau proteins (tangles) found in AD [32]. DLB is associated with dysfunction of the lower brain, brainstem, and subcortical, paralimbic, limbic, and cortical structures vital to movement and cognition. The severity of symptoms fluctuates over time, with improvements and regressions [28]. However, this dementia will eventually progress to catastrophic disability and death, as with AD.

The damage seen in AD is caused by changes in three major processes. The first process is the communication between neurons. Successful communication depends on reliable neuronal functions and the production of neurotransmitters. Any disruption of this process interferes with the normal function of cell-to-cell communication. The second process is cellular metabolism. Sufficient blood circulation is required to supply the cells with oxygen and nutrients such as glucose. The third process is the repair of injured neurons. Neurons have the capacity to live more than 100 years, but they must continuously maintain and adapt themselves in order to survive. If this process slows or stops for any reason, the cell cannot function properly.

Traditionally, predicting the occurrence or onset of dementia has been thought to follow the threshold model. This model holds that individuals will exhibit dementia only when their functional cognitive reserve falls below a certain specific threshold. According to this theory, the brain has a certain density or reserve and functions well so long as the reserve is sufficient. Reserve capacity is considered largely an individual matter, and according to this theory, it may be replenished with cognitive exercises.

According to research studies published by Mount Sinai Medical Center, the combination of heavy smoking and drinking may reduce the onset age of AD by six to seven years [37]. Fortunately, behavioral habits can be prevented or terminated and the associated risk factors reduced. Heavy smoking was defined as one pack of cigarettes or more per day, and heavy drinking was defined as two or more drinks per day. Further, the researchers noted that heavy smokers and drinkers with the ApoE4 gene had a tendency to develop AD 8.5 years earlier than those without these three risk factors, translating to an onset age of 68.5 years compared to 77 years for those not in the high-risk group [37].

Chronic worry and chronic high stress are more likely to be found among individuals who develop dementia than those with calmer and unworried personality types [40,41]. Prolonged exposure to elevated stress hormones may cause damage to critical areas of the brain, especially in certain racial/ethnic groups [40]. Patients who are chronically depressed, live overly stressed lives, and are prone to obsessive worry are at a greater risk for dementia. Such individuals should be directed into psychotherapy or other programs to address their specific risk factors.

Diet and nutrition may influence dementia onset and symptoms, and a relationship between AD and certain nutritional deficiencies has been suggested. For example, low vitamin E intake from food sources is associated with an increased risk of AD [47]. Oxidative damage, a major component of AD progression, is greatly reduced in individuals with adequate dietary vitamin E intake, and although other antioxidants and antioxidant cofactors are thought to have a protective effect, consistent data regarding the efficacy of vitamin C, flavonoids, and carotenoids, for example, is lacking. Research so far has shown that vitamin E supplementation does not offer protection equivalent to dietary intake of vitamin E, although it has been suggested that supplementation levels used in studies were too low [47,48]. Low vitamin B12 and folate levels have been suspected for increasing AD risk; however, folate deficiency is rare in the United States due to widespread use of enriched grain products [47]. Therefore, it is suggested that high folate intake combined with low B12 levels may instead be a risk factor for AD.

Fat composition is also suspect. High saturated or trans fat intake and low polyunsaturated and monounsaturated fat intake can cause hypercholesterolemia, a risk factor for AD [47,49,50]. Omega-3 fatty acids (especially docosahexaenoic acid or DHA) are protective against inflammation, oxidative damage, and synaptic loss. Individuals consuming one fish meal per week are better protected against dementia than those eating fish less often [47]. In a sample of 3,759 subjects 65 years of age and older, those who adhered closely to a Mediterranean diet (i.e., a diet high in fruits, vegetables, whole grains, fish, and monounsaturated fats) had a slower cognitive decline than those who ate such a diet more randomly or infrequently [51]. High-cholesterol foods should be generally avoided, with a greater focus on vegetables and fruits.

At least four genes have been implicated in the development of AD, including the amyloid precursor protein (APP) gene, ApoE4, and the presenilin 1 and 2 genes [56]. APP is a protein from which beta-amyloid, the chief component of plaques seen in the brains of patients with AD, is formed, while ApoE helps transport cholesterol in the blood [54]. Mutations of the presenilin 1, presenilin 2, and APP genes cause early-onset, autosomal dominantly inherited AD; mutations on chromosomes 1, 14, and 21 account for the majority of all of these cases [15,58]. ApoE4 is found in about 40% of the cases of late-onset AD [15]. It is possible to test family members with no symptoms of the disease to determine whether they carry the mutated gene, thus ascertaining their risk for developing AD. As noted, if the carrier is also a smoker and/or heavy drinker, the onset age of AD is likely to be earlier [37].

Symptoms seen with AD are partially the result of damage to the hippocampus and the cerebral cortex. The size of brain, especially the size of the hippocampus, may contribute to dementia risk. Memory storage and formation is primarily centered in the hippocampus, and neurofibrillary tangles generally build up in the hippocampus before moving to other portions of the brain. In one study, those with larger brains and larger hippocampi were found to have less brain plaque and fewer tangles. Hence, they tend to be less likely to develop AD. If true, it may be that some individuals are born with larger brains and hippocampi, which require more plaque in order for memory functions to break down. Alternatively, some other factor may protect certain brains from shrinkage and/or tangle formation [59,60,61].

While scholars agree that there may be several environmental factors for AD, no exposures, including pesticides, general air pollutants, lead, microplastics, and other toxins, have been positively linked to this form of dementia. Taking proactive steps to prevent oxidative damage, improve vascular health, and create a healthier lifestyle overall, seems to be the best defense against many environmental risks.

Presentation of AD is widely varied in patients, with symptoms and deficits affecting every individual differently or not at all. The primary diagnostic signs of advancing dementia and AD include, but are not limited to, the following:

Recent memory loss that affects the job, daily living, and/or interpersonal relationships

Short-term memory loss being greater than long-term memory loss

Difficulty performing familiar tasks

Expressive and receptive language problems

Becoming lost in the midst of a sentence or train of thought

Confusion in relating complex stories or themes

Disorientation of time, person, and/or place

Poor or decreased judgment

Problems of abstract reasoning

Misplacing things, even items with a usual location

Mood, personality, and behavior changes

Loss of initiative, including passivity and resistance to prodding to get involved

Mental status examinations alone are not definitive for establishing a diagnosis of AD; however, they are central to the diagnostic process and provide important information for developing a more complete clinical picture. Additionally, assessment offers a baseline for monitoring the progression of the disease and can be used to reassess mental status in people who have delirium or depression upon initial evaluation. All behavioral and psychologic symptoms should be assessed and documented.

Single photon emission tomography (SPECT) and positron emission tomography (PET) are noninvasive imaging techniques that provide information about cerebral function and regional cerebral blood flow. Cerebral glucose metabolism can be studied with PET using fluorodeoxyglucose [74]. The ability to image the regional metabolism of the brain and locate areas of diminished function has been of particular importance in advancing the ability to diagnose AD. These techniques help to differentiate AD from other causes of dementia but should not be used as the primary diagnostic measure [54,76,77,78,79,96]. One of the benefits of these tests is the ability to help identify people in the early stages of AD or those with MCI who may benefit from treatments that are now being offered or may soon be developed.

In the preclinical stage, the goal of management for susceptible patients is to prevent and/or delay the onset of the disease. Maintaining a healthy diet and lifestyle, with goals of reducing oxidative stress and blood pressure and improving circulation, may help to prevent dementia or slow the rate of disease progression [84]. Dietary, exercise, and pharmacologic treatment guidelines for lowering the risk of obesity, diabetes, cardiovascular disease, and particularly hypertension should be followed, as comorbidities complicate AD treatment and exacerbate the disease process. As noted, there is some evidence that certain nutrients, especially omega-3 fatty acids, can reduce the risk of dementia [85]. Engagement in cognitive activities is also highly recommended.

Older Americans are at an increased risk for suicide. Individuals older than 65 years of age comprise 16.8% of the population but represent 20.0% of all suicide deaths. The rate of suicides for the elderly in 2021 was 17.3 per 100,000, with one elderly suicide every 54.5 minutes [91]. Persons older than 85 years of age, especially white men, have the highest rate. Although the elderly attempt suicide less frequently than other age groups, they have a higher completion rate [91]. Common risk factors for suicide in the elderly include [91]:

Recent loss of a loved one

Physical illness, uncontrollable pain, or fear of prolonged illness

Perceived poor health

Social isolation and loneliness

Major changes in social roles (e.g., retirement)

The risk of driving-related accidents is increased among the older population, and impaired mental status due to cognitive impairment and/or the effects of certain medications can increase risk further. Restricting an individual's driving causes a considerable loss of independence and can be a highly sensitive issue, and the decision should be collaborative, if possible. A dementia diagnosis alone is not considered grounds to revoke driving privileges. Other factors must be present, including cognitive decline and comorbidities [101]. Many states require physicians to report impaired drivers, especially if there is a history of a closed head injury. However, laws vary regarding reporting by other service providers. Professionals are encouraged to study their own state's laws. There are driving schools and classes in many communities specifically designed to assist the elderly in maintaining their driving skills and license, which may be an option for some individuals.

Medication management and polypharmacy are major concerns for older adults. An estimated 30% of individuals older than 65 years of age take five or more prescription medications [102]. This number does not take into account over-the-counter medications, vitamins, minerals, and dietary supplements. Taking multiple medications and supplements significantly increases the risk of interaction with foods, other medications, and alcohol.