With “neurocognitive disorder”, more commonly known as “dementia”, we mean a degeneration of intellectual, memory and learning abilities, often related to behavioral alterations, that prevent those who suffer from it to perform the most common daily activities, keep normal productive interpersonal relationships, communicate and lead an autonomous life.
There are many forms of neurocognitive disorder, similiar by manifestations, but induced by different mechanisms. All forms of dementia are connected to the presence of a brain damage that may establishes itself acutely (such as in the case of a stroke) or gradually accumulate through decades and starts showing once passed a certain “edge”, beyond which the parts of the brain that are still healthy are no longer able to compensate cognitive functions lost because of the lesions. In this second case, we talk about cognitive age-associated decline, that may be mild and fairly manageable for many years or represent the first phase of a neural degeneration that will lead to a more severe dementia within a short period of time. The neural losses that we can observe in the aging brain are not all pathological: partly, they are connected to the natural aging and they arise even in healty subjects who will never develop any form of dementia.
The neurocognitive disorder/dementia begins when to the physiological brain empoverishment are added aggravating damaging factors such as, for example, specific pathological processes of different kinds (production of toxic endogenous compounds, celebral circulation alteration etc.), accidental traumas (especially strong hits to the head, especially if repeated) or toxic insults by substances or active drugs on the central nerve system (alcohol, illegal drugs, hypnotics, neuroleptics etc.). The intensitiy and speed with which the neural and cognitive decline develops and progresses are not pre-established but may vary among people according to a combination of phatological and traumatic factors and of the individual's genetic characteristics.
The main kind of neurocognitive disorders that may arise with the aging are:
Mild cognitive decline
With aging, having trouble remembering errands and dates or learning new concepts and being physically less reactive is a normal phenomenon not to worry about, within certain limits. However, when memory difficulties start creating problems in one's daily life and keeping one from peacefully executing common activities, it is important to talk to a physician. It may be mild neurocognitive disorder (also known as “mild cognitive impairment”): a kind of memory and learning impairment not particularly serious on its own but that deserves an evaluation and an early treatment because it may increase the chances of developing Alzheimer's disease in later years. At the moment nobody actually knows the basic causes of mild cognitive impairment.
As for any form of more severe dementia, it is thought that the origin may be complex and that involves:
- toxic factors for nerve cells such as amyloid beta protein, Tau protein and Lewy bodies (especially those that are present in the cerebral areas responsible for memory and learning),
- a reduced efficiency of the neural metabolism (particularly regarding the use of glucose),
- volume reduction of some key areas for memory, learning and planning (such as the hippocampus and the frontal cortex),
- cerebral blood flow alterations, such as those caused by localized micro-strokes or more common cases of arteriosclerosis.
Beyond the age of 60, the main risk factors for mild cognitive decline development are:
- genetic predisposition,
- high level of cholesterol in the bloodstream,
- sedentary lifestyle,
- lack of intellectual/social stimuli.
The main symptoms potentially connected to mild cognitive decline involve:
- initial difficulties in remembering episodes that happened within a few days, weeks or months or in keeping new information,
- trouble concentrating/high distraction during reading, film viewing, conversation, etc.,
- difficulty in taking decisions that didn't cause problems before, in planning activities fairly complex, understanding/following instructions (for example, the functioning of an electric appliance),
- occasional moments of confusion while out of the house,
- higher tendency to react on impulse,
- depression or loss of interest in habitual activities,
- anxiety and/or irritability,
- sleep disorders (insomnia or increase need for sleep).
In order to indicate a disease, these symptoms must be so intense that they create a certain uneasiness in the daily life (but without compromising the person's autonomy) and last in time, without being justified by specific causes such as an illness, the consumption of specific drugs or substances (alcohol etc.), a state of psychophysical debilitation or excessive stress at home or at work.
Treatment of mild cognitive impairment
In order to keep better and longer intellectual performances, it is possible to act on risk factors, reducing their negative impact by following good life rules (a balanced diet, rich in fruit and vegetables, fish, whole cereal, vegetable oils and dried fruit; regular physical activity; little alcohol, no smoking, control of body weight) and specific therapies (especially in case of hypertension, hypercholesterolemia and diabetes).
Other important prevention strategies consist in keeping yourself active (by reading, attending exhibitions, cinema and theater, using technological devices etc.) and dedicating yourself to interactive activities on a family and social level (taking care of grandchildren, volunteering, following any kind of class, planning group parties and travels).
A very important aspect to take into consideration concerns the potential presence of depressive symptoms that may not only determine a serious decay of the quality of life but also promote a patient's quicker cognitive and functionality deterioration. It's been proven that treating depression, especially with antidepressants, helps increase memorization abilities and manage the everyday routines.
Unfortantely, despite intense reaserches, there still are not yet available effective therapies able to stop the evolution of the neurological and cognitive decline once it starts. However, there are some pharmaceutical interventions and specialized neurorehabilitation that, if started at an early stage, may help slow down the progression of the neurocognitive disorder, allowing the person to be autonomous for a longer period of time.
Furthermore, clinical studies have confirmed that even the treatment with nutraceutics such as those based on antioxidants, neuroprotectives, antidepressants and those that apply to emotional states (for example bacopa, saffron, theanine, vitamins – especially B-group vitamins -, choline, omega-3), have proven effective in slowing down the aging process and decline of the central nervous system.
Neurocognitive disorder due to Alzheimer's disease
The disease takes its name from Alois Alzheimer, a German neurologist who for the first time in 1907 described its symptoms and the neuropathological aspects. At the autoptic exam, the physician noticed specificic signs in the cerebral tissue of a woman who died after an unusual mental disease. In fact, he highlighted the presence of buildup, later called amyloid plaques, and bundles of tangled fibers, the neurofribrillary tangles. Today the plaques formed by amyloid proteins and the tangles are considered the effects on the nervous system of a disease of which, despite great efforts, the causes are still unknown.
The neurocognitive disorder due to Alzheimer's disease is the most common form of dementia connected to aging, causing about 50-60% of all the cases of cognitive impairment in advanced age. At the moment, the amount of people globally affected by this disease are about 36,5 millions (600.000 in Italy) and their number is inevitably going to increase beause of the progressive lengthening of the average lifespan and percentage of elderly people.
According to official estimates, in 2050 people affected by Alzheimer's disease will be about 115 million worldwide.
Alzheimer's disease starts to develop in most cases after the age of 60 (7% of the cases between the age if 65 and 74; 53% between 75 and 84; 40% after 85), with an effect that doubles every five years, starting to affect around one persone out of 3-4 after the age of 80. The disease affects with comparable frequency men and women, but the latter are often more affected becuase of their longer lifespan. The chance of developing the neurocognitive disorder due to Alzheimer's disease is, partly, connected to the individual's genetic characteristics, but only in 2-3% of cases hereditary forms can be traced.
Of the potential genes involved in the devolpment of Alzheimer's disease, the only one of which we have sure information, is the alipoprotein e4 (APOE-e4), that represents a risk factor for the early development of the disease and a diagnosis support in people who already show cognitive and behavioral symptoms, but not a specific diagnistic marker since its presence is not enough on its own to cause neurodegeneration.
At this day, the exact origin of Alzheimer's disease is unknown. We've known for a few years, however, that its insurgency is mostly linked to the accumulation, respectively within and without the neurons in the brain, of two specific proteins called beta-amyloid and Tau protein. Both these substances excert a toxic action that causes a more rapid death of the nerve cells, especially those that are in brain areas important for memory (hippocampus and amygdala), interfering with the capability of acquring and keeping information. Who suffers from it, therefore, has difficulties with remembering recent events and learning new concepts.
With the evolving of the disease, memory and learning progressively worsen and the neurodegeneration also affects other brain areas that manage space-time orientation, behavior, mood, communication abilities and the ability to perform all these “complex” operations that prove essential to be autonomous in the daily life, such as cooking, buying groceries or taking care of yourself.
The average duration of the disease varies between 8 and 20 years, according to the onset age and the neurocognitive and global physical decline.
The main symptoms connected to the neurocognitive disorder due to Alzheimer's disease that must push a person to ask for a specialized evaluation by a neurologist of a UVA (Alzheimer's unit evaluation) are:
- difficulties with remembering recent events (that happened within a few days, weeks or months) or new information,
- orientation in space and time difficulties (trouble remembering the way home, day of the week, month etc., or evaluating the time of the day; mental overlapping of events that happened in different moments),
- language disorders (trouble talking and expressing yourself),
- thought disorders (mental confusion),
- coordination and movement disorders (with resulting problems with performing activities such as dressing up, washing yourself, cooking etc.),
- depression and/or irritability,
- impulsive/violent reactions.
In order to indicate the disease these symptoms must have an intensity so great that they significantly interefere with the daily life, not be connected to the presence of other physical or psychiatric diseases or the intake of drugs or substances, and last in time, progressively worsening, although at variable speed and intensity.
On the basis of symptoms, personal and family anamnesys and clinical evaluation, the physician may believe to be seeing a case of “possible” Alzheimer's disease.
In order to get a more precise and reliable diagnosis of “probable Alzheimer's disease” (at this day, by law, in order to have a certified disease it is still essential to take an anatomopathological examination of the post mortem brain tissue), the neurological visit must be completed with the analysis of the cerebrospinal tissue and the neuroradiological examination of the encephalus with functional magnetic resonance imaging (fMRI) or positron emission tomography (PET), other than, if possible, a research of the APOE e4 gene.
The certainty of the disease, by law, can only be decided post mortem, after the anatomopathological examination of the brain tissue and after having observed buildups of beta-amyloid and Tau protein and other typical alterations, such as cerebral cortex atrophy.
Treatment of Alzheimer's disease
Despite all the research done in the last decades, for Alzheimer's disease it hasn't been possible to find an appropriate treatment. Initial interventions that can now be proposed to patients, if performed during the initial stage, can diminsh the disease's symptoms for a certain period of time, but cannot slow down or modify the global course. The main available approaches are based on the adminisration of some drugs with neuroprotective action or oriented to reduce behavioral symptoms and functional/cognitive rehabilitation-based.
Medications that are now available to diminsh the symptoms of Alzheimer's disease are most commonly the acetylocholinesterase anticholinesterase inhibitors (rivastigmine, donepezil, eptastigmine and galantamine) and memantine: the first ones act by increasing cerebreal concentration of acetylocholine (one of the substances involved in memorization mechanisms) and are useful in the initial stage; the second one reduces the stimulation of NDMA glutamate receptors (another cerebral neurotransmitter) and it is indicated in the intermediate and advanced forms of the disease. Antipsychotic and sedative compounds can, furthermore, be necessary along with acetylocholinesterase anticholinesterase inhibitors to ease behavioral disorders, especially anxiety, aggresiveness or apathy, that in some stages of the disease can create considerable management problems to family members and caregivers, other than patients. All these pharmacological therapies are refunded by the National Health System (NHS) but only if the patients have received a diagnosis of “probable Alzheimer's disease” and are followed by neurologists of Alzheimer's Evaluation Units (UVA).
Vascular neurocognitive disorder (vascular dementia)
Vascular neurocognitive disorder (vascular dementia) is a form of cognitive deficit caused by an alteration of the brain blood flow following acute events such as a stroke or cerebral hemorrage or chronic pathologies such as artherosclerosis. As in other kinds of dementia, in this case as well the decay of the intellectual capabilities depends on a degeneration of nerve cells that are present in the cerebral area affected, but to determine the neural damage in this case is mostly the lack of an adequate feeding of oxygen and nutrients (especially glucose). Beyond the age of 60, the risk of stroke or chronic cerebrovascular pathologies and later the development of vascular dementia is increased by the presence of diabetes, hypertension, high level of cholesterol in the bloodstream, heart diseases (especially miocardial infartation history and atrial fibrillation) and smoking. Generally, men tend to be affected by vascular dementia more often then women, especially after the age of 70.
The symptoms can manifest themselves in presence of vascular neurocognitive disorder (vascular dementia) and may vary by patient according to the affected specific brain area affected by the reduction of blood flow and can involve behavioral/cognitive manifestations and motor disorders of various nature and seriousness. Their onset can be sudden (such as after a stroke) or slow and characterized by progressive worsening (for instance in case of repeated micro-strokes or in case of widespread artherosclerosis).
The most common behavioral and cognitive symptoms are:
- mental confusion,
- concentration difficulties and easy distraction,
- difficulty in taking decisions and planning fairly complex activities,
- learning and memory problems,
- language difficulties,
- balance issues,
- increased urination need or problems with the contro of the stimuli,
- higher tendency to have impulsive reactions,
- anxiety and/or irritability,
As in the case of neurocognitive disorder dueto Alzheimer's disease, for vascular dementia as well a diagnosis of “possible” vascular neurocognitive disorder may be performed on the basis of the symptoms, personal and family anamnesis and general clinical evaluation, whereas for a more reliable diagnosis of “probable” vascular neurocognitive disorder a neurological examination must be completed with the execution of a neuroradiological examination of the encephalus with MRI, functional magnetic resonance or positrion emission tomography (PET).
When the cognitive deficit arises after a stroke, performing a diagnosis of vascular dementia is fairly easy and it doesn't necessairly require instrumental investiagations (though desirable for a better evaluation). On the contrary, in forms of slow progressive/fluctuating vascular dementia onset the differential diagnosis regarding Alzheimer's disease may be troublesome and complex also because the two pathelogies not rarely coexist. Because of this reason the physician, aside from the physiological evaluation and cerebral imaging tests, will also prescribe a series of further clinical examinations such as blood and cerebrospinal fluid tests, carotid ecodoppler etc.
Treatment of vascular dementia
At the moment there are no specific treatments available to fight vascular dementia after its onset. It is possible, however, to try to stop the evolution of the brain damage and avoid that the situation quickly gets worse by reducing the negative impact of the main risk factors, through good life rules (a balanced diet, rich in fruit and vegetables, fish, whole cereals, vegetable oils and dried fruit; regular physical activity; little alcohol, no smoking, body weight control) and specific therapies (especially in case of hypertension, hypercholesterolemia, diabetes and heart diseases). A very important aspect to take into consideration concerns the potential presence of depressive symptoms, that may not just cause a serious decline of the quality of life, but also promote a rapid worsening of the intellectual performances and the global functioning of the patient. In these cases, it is possible to recommend the assumption of antidepressants. In some patients with vascular neurocognitive disorder, the neurologist can also decide to administrate authorized drugs for the treatment of Alzheimer's disease, such as acetylocholinesterase anticholinesterase inhibitors and memantine. These medications can be refunded by the National Health System only when prescribed by neurologists operating in Alzheimer's Evaluation Units.
Cognitive impairment due to Parkinson's disease
A specific kind of neurocognitive disorder, still of unclear origin, is the one associated to Parkinson's disease, a neurodegenerative disorder that affects brain cells that produce dopamine, that firstly determines movement disorders (especially tremors while at rest, slowing of movements, muscle stiffness and dyskinesias), but it also connects to a series of “non-motor” symptoms such as speech impairment, sleep disorders, depression/anxiety and, sometimes, compulsive behavior. Parkinson's disease arises typically after the age of 60, more often affecting men rather than women with its prevealence in constant increase because of the progressive aging of the population. Based on epidemological data, in the USA Parkinson's disease affects 0.5% of the people between 65 and 69 years of age and 3% of the people over 85.
In the last years it's been understoond that the neurocognitive decline disorder due to the Parkinson's disease is more common that what we thought in the past and it may already establish within the initial stages of the disease (in this case we talk about Lewy bodies neurocognitive disorder). According to estimates, at least 25-30% of all the patients suffer from it, with a higher frequency amongst the elderly and those with advanced forms of Parkinson's disease. Recognizing the symptoms from the beginning is important because this form of neurocognitive decline, just as the neurocognitive decline caused by Alzheimer's disease, drastically increases the risk of developing dementia in later years.
Unfortunately, delivering a specific early diagnosis of the neurocognitive disorder in the parkinsonian patient is not easy because the most common early symptoms (minor memory loss, difficulty in concentration and distraction, slow reflexes, mental confusion, low interest in daily activities etc.) are similar to the intellectual and behavioral modifications that happen during aging in healthy people or are easily connected to side effects of therapies used for controlling the base disease, in presence of a mild form of depression or as consequences of an inadequate night of sleep.
According to the criteria provided on the psychiatric diseases statistics diagnostic manual – DSM V, in order to agree that a person is affected by neurocognitive disorder due to Parkinson's disease, intellectual and behavioral symptoms must occur progressively after a sure diagnosis of Parkinson's disease and after excluding possible side causes.
Among the smyptoms supporting the diagnosis of the neurocognitive disorder caused by Parkinson's disease we must mention:
- depressed and/or anxious mood,
- personality changes,
- behavior alterations
- sleep disorders,
- excessive daily sleepiness.
Treatment of cognitive decline connected to Parkinson's disease
At the moment there are no treatments able to efficiently stop the mild cognitive decline in a patient affected by Parkinson's disease. However, the optimization of anti-Parkinson's therapies, a healthy diet, moderate but regular physical activity (compatible with the limits imposed by the disease) and an emotionally and intellectually stimulating life environment may have a favorable influence on the cognitive side, contributing furthermore to improve the mood and the global quality of life of the ill patient. When, in the most advanced stages of Parkinson's disease the cognitive decline starts becoming clearer it is possible to intervene with drugs that are similar to those used for Alzheimer's disease. In Italy, it is approved with this indication the acetylochlinesterase or anti-cholinesterase rivastigmine. Furthermore, some studies have shown that in the parkinsonian patients anti-Alzheimer medications (such as donepezil and, in small measure, memantine) may have a double beneficial effect, not only improving the cognitive and behavioral symptoms but also the motor symptoms. These are, however, therapeutic options that must be evaluated case by case, after a careful risk/benefit calculation, in the context of the treatment's global plan.
Dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is a progressive neurogenerative disease; it is clinically characterized by dementia, cognitive function and awereness fluctuations, halluciniations (visual) and parkinsonism. The occuring of DLB has been estimated in 1/893 people/year. DLB is not considered a rare disease. In the general population, the estimated complessive prevalence considerably varies from 1/5882 in Japan to 1/135 in Finland. In the general population over the age of 65 the prevalence varies: from 1/1000 to 1/20 individuals and from less than 1/59 to 1/3 individuals with dementia (> 65).
In the initial stages, DLB cannot be easily distinguished from Parkinson's disease (PD) and rarely resembles Alzheimer's disease (AD). At the beginning, unlike what happened in AD, patients with DLB often do not show memory degeneration, but rather a damage of executive functions. Cardinal clinical signs are:
- fluctuating cognitive decline, very noticeable attention, conscience and awereness fluctuations,
- hallucinations (visual),
- PD symptoms.
DLB diagnosis indicators are symptoms such as:
- recurring tripping/falling,
- momentary loss of conscience,
- systemic delirium,
- REM sleep behavior disorders,
- severe disfunction of the autonomous system, with incontinence and orthostatic disregulations.
The diagnosis requires an attentive clinical evaluation based on internationally established diagnostic criteria and on the patient's medical history. The diagnostic certainty is increased by the evidence of a dopaminergic recaptation diminished in basal ganglia, visible through SPECT with FP-CIT (DaTSCAN). Other noticeable signs of DLB are the absence of temporal atrophy to MRI and REM sleep disorders (EEG). EEG may show an early generalized braking of the basic activity, with anomalous transients in the temporal lobes or the presence of frontally dominating bursts. In a few rare cases, the miocardial scintography may reveal the sympathic denervation. There is a wide clinical overlapping between DLB and AD, that sometimes may take to the diagnosis of the 'in-between' variant of the Alzheimer's disease by Lewy bodyes. If the PD symptoms precede the cognitive decline by 12 or more months, the disease is called PDD (not DLB), even if it's an arbitrary definition, shared among clinicians and it doesn't have an official definition. The retrospective history may be troublesome in DLB. The differential diagnosis is put on the hydrocephalus with normal pressure (see this term) (present in 1/10 patients with dementia).
It is important to perform an early diagnosis because of the therapeutic complications. Although a solving treatment is not yet available, the cholinesterasis inhibitors may considerably ease the symptoms on some patients, but at the moment there are no large-scale ezperimentations. In order to ease PD symptoms, it is usually recommended levodopa monotherapy. Atypical neuroleptics are essential to the symptoms undertaking and must be administered at a low dosage. DLB is a progressive dementia. The life expectancy is about 8 years from the onset, even though it may vary according to the phenotype.
The prevalence of dementia in industrialized countries is about 8% in people over 65 and grows up to 20% over the age of 80. According to some projections, the cases of dementia may triple in the next 30 years in Western countries.
Dementia is constantly growinh in the general population and has been defined according to the OMS Report and ADI as a global priority of public health: “in 2010 35,6 million people resulted affected by dementia with an estimate of twice the number in 2030, three times in 2050, with 7,7 million new cases every year (1 every 4 seconds) and an average survival after the diagnosis of 4-8 years. The costs estimate is 604 billion dollars/year with a progressive increase and a permanent challenge for the health systems. All countries must include dementias in their public health programs; on the international, national, regional and local level programs and coordination on more level and amongst the interested parties are necessary.” (Geneva April 11th 2012).
The consequences on an economic and organization level are easily imaginable, considering that just the annual costs for each patient are estimated, in many European studies, in variable numbers such as 9.000 to 16.000 euros according to the stage of the disease.
Texts have been taken and reworked from
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