Department of Psychology, Italy
*Corresponding author: Giulio Perrotta, Department of Psychology, Italy
Submission: March 13, 2020;Published: May 07, 2020
ISSN 2578-0093Volume6 Issue1
This work focuses on the specific analysis of the general, neurobiological and clinical profiles of human dementias, starting from classifications and definitions, and then extending the field of study to clinical and psychological symptomatologic data, to conclude with treatments and better management of these patients.
Definitions and classifications  "Dementia" is a global, chronic and irreversible cognitive deterioration, even if with a correct diagnosis and targeted therapy it is possible to slow down the progression of the disease. The diagnosis is therefore clinical, through laboratory tests and the study of MRI images, starting from the symptoms described in the anamnestic history. The treatment, therefore, is supportive, precisely by virtue of the chronic, progressive, disabling and irreversible nature of this family of pathologies. Dementia can occur at any age but mainly affects after the fifth decade of life. Based on the data found in the anamnesis, dementias can be classified into:
However, "dementia" should not be confused with other more or less pathological forms:
"cognitive symptoms related to depression": these cognitive disorders are resolved with the treatment of depression. Elderly depressed patients may experience cognitive decline, but unlike dementia patients, they tend to exaggerate their memory loss and rarely forget important or personal events. Neurological examination is normal except for signs of psychomotor slowdown. When evaluated with tests, patients with depression make little effort to respond, while those with dementia try hard even if they respond incorrectly. When depression and dementia coexist, the treatment of depression is not able to completely regress the cognitive disorder.
In detail, the "main dementia forms":
Alzheimer's : It is the most common chronic progressive and disabling degenerative neurocognitive dementia (between 50% and 70%), closely connected to deposits of amyloid plaques and neurofibrillary tangles, capable of causing the following symptoms, divided into four specific phases: 1) pre-dementia (short-term memory deficit and inability to acquire new information; 2) initial phase (language deficit such as impoverishment in vocabulary and decrease in fluency of speech, agnosia, apraxia, decreased coordination ability muscle, with less damage in episodic and implicit memory); 3) intermediate phase (aphasia, disorientation, inability to deal with daily activities, long-term memory deficit, sensory dysfunction, mood swings, depression); 4) final phase (total dependence on the caregiver, muscle weakness, inability to feed independently, death from infection or neurovascular damage). The prognosis is 3-9 years.
Chronic traumatic encephalopathy : Also known as boxer dementia, it is a dementia caused by anomalies of the Tau protein, following repeated head injuries and concussions, capable of interfering with the normal metabolism of neurons. Symptoms that distinguish the syndrome include tremors, ataxia, dysarthria and pyramidal lesions, also alteration of the personality, with consequent outbursts of anger, delirium, and obsessive jealousy. The prognosis is 2-5 years.
Frontotemporal dementias : Also called in DSM-5 with the term "major or mild frontotemporal neurocognitive disorder", this phrase identifies a heterogeneous group of non-Alzheimer's neurodegenerative dementias that are characterized by the presence of degenerative-atrophic alterations of the frontal and temporal brain lobes. It is an umbrella term for different pathologies or alternatively a pathology with different variants. Symptoms such as sudden personality changes and behavioral-motor oddities in the absence of pre-existing psychiatric or neurological pathologies, and only afterwards for a partial memory loss, together with the growing cognitive and motor deficit, are reported. Average survival is approximately 6-8 years, based on the specific form and timing of intervention. Typical forms are:
Primary progressive aphasia : It is a progressive speech disorder that, although it is part of the frontotemporal dementia, differs from semantic dementia in the most severe aphasia and in the absence of personality, behavior and anosognosia disorders, although dementia invariably occurs in late stages of illness. The prognosis is 8-15 years.
Semantic dementia : Unlike primary progressive aphasia, aphasia is moderate in this pathology where fluency or the ability to find words is not corrupted. Rather, there is a progressive loss of the meaning of words, very often associated with paraphasia’s and prosopagnosia. The disinterest in personal care, persevering attitudes and compulsiveness, identify this nosologically entity in the context of frontotemporal dementia. This link is strengthened by the presence of impaired mnemonic functions only in late stages of the disease. The prognosis is 8-15 years.
Progressive supranuclear palsy : Neurodegeneration involves atrophy at the level of the midbrain and other brain structures including the subthalamic nucleus, the Globus pallidus, the nuclei of the bridge and the black substance. The name of the disease describes the supranuclear localization (with reference to the oculomotor nuclei of the midbrain) of pathological changes. The term 'nucleus' refers to the group of neurons from which the oculomotor cranial nerves that connect the midbrain and extrinsic muscles of the eye originate. While a paralysis of the oculomotor nerves can be caused by lesions of the nerves themselves or by lesions at the level of the nuclei, in the case of supranuclear palsy the cause is located in the brain, above those structures. The onset can be non-specific, with an often symmetrical and rigid-bradykinetic extrapyramidal syndrome, but in 2/3 of the cases there is a disturbance of the balance with a tendency to retropulsion, postural instability and frequent falls. More rarely the onset occurs with ophthalmoplegia and other truncal signs. In the more advanced stages of the disease, the appearance of the typical supranuclear ophthalmoplegia makes the clinical picture more characteristic: there is paresis of the gaze vertically (both downwards and upwards). In the late stages, voluntary eye movements are missing, but ocular-vestibular reflexes are discreetly preserved (thus giving rise to the so-called doll-eye phenomenon: the gaze is immobile even when the head is turned passively, the eyes always point in the same direction - therefore a automatic movement of the eyeballs stimulated by the vestibular system, while voluntary control of eye movement is no longer possible). Blinking rarities and oculo-eyelid apraxia may also occur. All this gives the patient an astonished appearance with the need to move the head to look around. The movements of the head are also reduced, however, as muscle stiffness is often particularly accentuated at the level of the trunk and cervical musculature. Thus, instead of the flexion posture typical of parkinsonians, on the contrary in PSP patients there is an attitude in extension, with stiff neck. Other signs are of the "pseudobulbar" type: dysarthria, dysphonia, dysphagia, with laughter and spastic crying (involuntary, not necessarily corresponding to the respective emotional states). There may be vivid or increased reflexes with bilateral Babinski phenomenon. Also common are signs of cognitive impairment, sometimes blepharospasm is present. Especially in the early stages of the disease, PSP can be difficult to distinguish from Parkinson's disease. The most important differences that allow to make the differential diagnosis are: both paralysis and Parkinson's disease give: rigidity, difficulty of movement, and clumsiness; generally, people with paralysis tend to tilt their heads backwards (and tend to fall backwards), while those with Parkinson's disease usually bend forward (interspersion); speech and swallowing disorders are much more common and severe in paralysis than in Parkinson's disease and also tend to occur earlier; eye movements are abnormal in paralysis, but are almost normal in Parkinson's disease; tremor is more characteristic for Parkinson's disease, while it is rarer in paralysis; people with Parkinson's disease have significant benefits with levodopa, instead people with paralysis do not respond to this drug or respond only transiently. The prognosis is 6-10 years.
Lewy body dementia : It is a neurodegenerative disease, a form of dementia similar to Alzheimer's disease, but with an earlier onset. It has close, but not completely clarified, relationships with Parkinson's disease, with which it shares some anatomopathological aspects: in fact, Lewy bodies are defined as anomalous deposits of fibrillary protein that form in nerve cells and are mainly located in the nuclei of the brain stem (Parkinson's disease) and cerebral cortex (Lewy body dementia). This disease also has some clinical aspects in common with Parkinson's, such as tremors and movement disorders, and it is now believed that the forms of Parkinson's disease associated with (or evolved in) dementia are nothing but Lewy body dementias start with parkinsonism. The symptomatology, although very varied, is characterized by large variations in the state of attention and alertness, with fluctuations present day by day and even hour by hour, cognitive disturbances, recurrent visual hallucinations (minor in typical Parkinsonian dementia), and characteristics motor skills. From a clinical point of view, the salient aspects of the disease are: cognitive impairment (with memory problems, semantic dementia and apraxia), characteristically fluctuating (not stable and progressive as in Alzheimer's, at least in the early stages), visual hallucinations, which often mark the onset of the disease, mood disorders (especially depression) and other neuropsychiatric symptoms (delirium, paranoia, anxiety, panic, not showing instead the typical disinhibition of frontotemporal dementias, even if it can be present just like in Parkinson's, nor hyperorality) and then the typical movement disorders which, indistinguishable from those of Parkinson's: tremor at rest, only sometimes kinetic, camptocormia (flexed forward position), Gowers trait (parkinsonian gait), rigidity, amimia, dysarthria, shuffling step; they are often more pronounced and disabling than in Parkinson's, but appear later. Patients are often also subject to hyper catabolism which, if left untreated, can lead to sudden and drastic weight loss. Sleep disturbances (dyssomnia and parasomnias) are frequent, both insomnia and hypersomnia: many patients have sleep behavior problems, manifesting physical reactions, sometimes becoming dangerous for themselves and others. The autonomic nervous system can dysregulate internal functions (dysautonomia), such as blood pressure and temperature: fainting, hyperhidrosis (excessive sweating) and anhidrosis (absence of sweating), xerostomia (dry mouth), incontinence or urinary retention may occur and constipation. The prognosis is 5-8 years.
Parkinson : It is a neurodegenerative disease. The typical motor symptoms of the condition are the result of the death of cells that synthesize and release dopamine. These cells are found in the substantia nigral, a region of the midbrain. The disease is characterized by the accumulation of a protein, called alpha-synuclein, in inclusions called Lewy bodies in neurons and by the insufficient formation of dopamine. The anatomical distribution of Lewy bodies is often directly related to the expression and degree of clinical symptoms of each individual. At the onset of the disease, the most obvious symptoms are related to movement, and include tremors, stiffness, slow movements and difficulty walking. Later, cognitive and behavioral problems can arise, with dementia sometimes occurring in the advanced stages. The prognosis is 5-15 years, but it depends on the age of the onset of the first symptoms.
Huntington : It is a neurodegenerative genetic disease that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically begins during middle age; it is the most frequent disease due to genetics in neurological clinical pictures with abnormal involuntary movements (which are called chorea). The symptoms of the disease can vary between individuals and even among affected members of the same family, but their progression can usually be predicted. The first symptoms are often subtle mood or cognitive problems followed by a general lack of coordination and an unstable gait. As the disease progresses, uncoordinated movements of the body become increasingly evident and are accompanied by a decrease in mental abilities and behavioral and psychiatric problems. Complications, such as pneumonia, heart disease and physical damage from falls, reduce life expectancy to around 10-15 years, starting with the onset of the first symptoms.
Binswanger disease : Also called subcortical vascular dementia, it is a form of dementia, particularly leukoencephalopathy. The most common feature of this disease is a psychomotor slowness. This is caused by damage in deep layers of the white matter of the brain and by arteriosclerosis, as well as by different types of gliosis (microgliosis and astrocytic gliosis), causing the atrophy of the white matter itself and the rupture of the subcortical neural networks, which control the executive cognitive functioning. It is a progressive degenerative disease that rapidly advances with sudden and gradual changes. The main symptoms are directly related to the breakdown of the neural networks. They include short-term memory loss, short-term attention, inadequate behavior, inability to make organizational and decisions, changes in mood and personality, and unstable gait (accompanied by frequent falls). In general, a common psychomotor slowness prevails. Other symptoms are: speech changes and urinary symptoms (unrelated to urological diseases). Life expectancy is 5-8 years.
Lacunar syndrome [12,13]: The anatomopathological term "lacuna" indicates a cavity filled with cerebrospinal fluid, less than 15mm, located in the gray nuclei, in the thalamus, in the semi-oval center or in the brainstem. Three types have been described: lacunar infarcts, lacunar hemorrhages and dilations of the perivascular spaces of Virchow-Robin. Most of the gaps are silent, but various clinical pictures can be found. The more specific ones are called "lacunar syndromes": pure motor hemiparesis, pure sensory hemiparetic, sensory-motor hemiparesis and ataxic hemiparesis. The diagnosis of lacunar infarction is faced with a lacunar syndrome associated with diagnostic data for images compatible with the occlusion of a single perforating artery, in the absence of another identified etiology. The most frequent cause of lacunar infarction is lipoylations of the perforating arteries, generally favored by chronic arterial hypertension. Lacunar infarcts account for a quarter of cerebral infarcts. The treatment of the acute phase is identical to that of the other cerebral infarcts. Secondary prevention includes antihypertensives, statins and platelet aggregation inhibitors. This subtype of cerebral infarction exposes to relapses and cognitive disturbances. The prognosis depends on the timing of surgery.
Vascular dementias [14,15]: They are cognitive deficit caused by an altered blood circulation in the brain, which deprives some areas of the organ of blood, causing the progressive and irreversible death of brain cells. The causes that can distort the normal blood vessel system inside the brain are different: the main one is the so-called small blood vessel disease (subcortical vascular dementia), but less common causes, such as stroke, should not be overlooked mixed dementia, multi-infarct dementia, CADASIL, hypoxic encephalopathy and atherosclerosis. The symptoms of vascular dementia can be very different from patient to patient, depending on the parts of the brain affected by the disease. The prognosis here too is highly variable but hardly exceeds the first decade of diagnosis.
Gerstmann-Sträussler-Scheinker disease : It is a very rare neurodegenerative disease (1-3 cases per 100 million) and of a purely family character with autosomal dominant inheritance, classified as transmissible spongiform encephalopathy. It is one of the few diseases that are caused by prions, a class of highly protease-resistant pathogenic mutated proteins. In the classic form, the mutation of the PRP protein occurs at the level of codon 102. In others, mutations at the level of codons 198,217 and 117 hesitate towards a form dominated by dementia and parkinsonism. Furthermore, a codon 105 mutation characterized by late dementia and spastic paraparesis is recognized. Symptoms develop slowly in the initial phase, with difficulty articulating words (dysarthria), progressive cerebellar ataxia and pyramidal signs, with postural instability and impaired motor function. Subsequently, the disease progresses with the accentuation of dementia. The prognosis hardly exceeds 5 years.
Fatal family insomnia [17-19]: It is an autosomal dominant prion genetic disease that leads to degeneration of the nucleus of the thalamus and cerebral cortex. The mutated PRNP gene encodes the PrPSc protein, which tends to fold in an incorrect way, called a prion form. Familial fatal insomnia is a degenerative brain disease belonging to the group of spongiform encephalopathies. It causes total insomnia (inability to sleep), which after a few months of suffering leads to death. It appears that the mechanism of disease onset is linked to hormonal changes, including an increase in catecholamines and cortisol, a lack of melatonin and a loss of the circadian rhythm of the pituitary gland. Furthermore, according to some scientific studies, the PrPc protein is a component of GABA receptors and its conversion into a protein isoform would cause the inability of the same receptors to exert their inhibitory action on the nerve cells of the thalamus, which, due to the 'excessive activation, would face necrosis. After a period of exhaustion, the patient begins to suffer from increasingly severe drug-resistant insomnia, up to the complete inability to sleep, which is followed by stupor and coma. However, in the stage where the inability to sleep occurs, there are apparently paradoxical sleep phases similar to sleepwalking, which are characterized by recited dreams. The disease progressively damages verbal and long-term memory but does not involve dementia. In addition to insomnia, motor difficulties (e.g. ataxic gait) and an early neurovegetative dysautonomia, with sphincter disorders, sialorrhea, watery eyes, constant sweating, runny nose, increased body temperature and blood pressure, tachycardia and changes in breathing (e.g. tachypnea), but sometimes paresis also appears. The prognosis is always unfavorable: the duration before death varies from 6 to 18 months, but on average it is around 12 months.
Creutzfeldt-Jakob and its western variant "nvMCJ" and aboriginal "Kuru" : It is a rare neurodegenerative disease, which leads to a form of fatal progressive dementia. Clinical syndrome is characterized by mainly cortical polysexual deficits with memory loss, personality changes, hallucinations, dysarthria, myoclonus, postural rigidity and convulsions. Creutzfeldt-Jakob disease is the most frequent form of human spongiform encephalopathy. The prognosis is usually less than 2 years.
Normotensive hydrocephalus [21,22]: Means a type of communicating hydrocephalus, in which the increase in intracranial pressure, due to the accumulation of the cephalorachidian fluid, becomes stable or the formation of cerebrospinal fluid is balanced with absorption; intracranial pressure gradually decreases, but still remains at a slightly elevated level. Due to this balance the patient does not show the classic symptoms of intracranial hypertension such as headache, nausea, vomiting or unconsciousness. However, the subject shows the classic triad: difficult gait, urinary incontinence and mental decay. The prognosis is variable and depends on the surgery.
Violent acts are not uncommon in patients with dementia, which are the main reason for the request for institutionalization. Disturbing actions include wandering, restlessness, shouting, throwing objects, physical violence, refusing treatment, incessant questions, hindering the work of staff members, insomnia and crying. Behavioral disturbances in dementia have not yet been well characterized in etiopathogenetic terms and the modality for their treatment is not fully clarified. Deciding which action constitutes a behavioral disorder is highly subjective. Tolerability (which actions the person assisting the patient manages to accept) also depends in part on the organization of the environment in which the patients live and in particular those relating to safety. For example, wandering can be tolerable if a patient lives in a safe environment (with locks and alarms on all doors and gates); however, if the patient is in an institution or hospital, wandering can be unmanageable since it disturbs other patients or interferes with staff activities. Many behaviors (for example, wandering, asking questions repeatedly, being uncooperative) are better tolerated during the day. It is not clear whether the sundowning (exacerbation of disturbing behavior at sunset or in the early hours of the evening) is due to a question of reduction of tolerability by the person assisting the patient or if it is a true diurnal variation .
Behavioral and psychological disorders can result from functional changes related to dementia: 
The best approach is to characterize and classify behavior, rather than labeling all of these behaviors as agitation, a term with too many meanings to be useful. The Cohen-Mansfield shaking ladder is commonly used; classify behaviors as follows: 
If behavioral variation is observed, an objective examination must be performed to rule out organic ailments and physical abuse, but also environmental modifications (for example, a person assisting the patient) must be considered, which may themselves be the cause of the disorder rather than a factor related to the patient. Depression, frequent among patients with dementia, can influence behavior and therefore must be identified. It may initially manifest as a sharp change in cognition, decreased appetite, mood changes, changes in sleep rhythm (often hypersomnolence), withdrawal, decreased level of activity, crying spells, death talk, sudden irritability or psychosis, or other sudden changes in behavior. Often, depression is first observed and detected by family members. Psychotic behavior must be identified because its management is different. The presence of delusions or hallucinations indicates psychosis. Delusions or hallucinations must be distinguished from disorientation, states of distress and misunderstandings that are frequent in patients with dementia: Delusions without paranoia can be confused with disorientation but the delusional content is usually fixed (for example, a medical residence is repeatedly called prison) while in disorientation it is variable (for example, a sanitary residence is sometimes called prison, then restaurant or house). Hallucinations occur without external sensory stimuli; hallucinations must be distinguished from illusions, which occur by misunderstanding external sensory stimuli (eg, cell phones, pagers) [24-28].
It is therefore evident that the best theoretical approach is determined by the perfect combination of medical therapy and supportive psychotherapy, to accompany the patient in the chronic, progressive and disabling evolution of the pathology. In particular, cognitive-behavioral and strategic therapy are more effective, together with drug therapy that acts on cognitiveness (for example, cholinesterase inhibitors), helping to better manage behavioral and psychological symptoms in patients with dementia. However, drugs that act predominantly on behavior (for example, antipsychotics) are used only when other approaches are ineffective and when they are critical to safety. The need for continuous treatment needs to be reviewed at least every month. Medicines must be selected to reduce the most intolerable behaviors. Antidepressants, preferably serotonin reuptake inhibitors, should only be prescribed for patients with obvious signs of depression. Antipsychotics are often used although their effectiveness has only been shown in psychotic patients. Other patients are unlikely to benefit from it and are likely to experience adverse effects, particularly the appearance of extrapyramidal symptoms. Tardive dyskinesias or tardive dystonia may develop; they often do not disappear with dose reduction or drug withdrawal. The choice of an antipsychotic is based on its relative toxicity. Among conventional antipsychotics, haloperidol is relatively low sedative and has less anticholinergic effects but is more likely to cause extrapyramidal symptoms; thioridazine and thixixene are less likely to cause extrapyramidal symptoms but are more sedative and have greater anticholinergic activity than haloperidol. Second generation (atypical) antipsychotics (for example aripiprazole, olanzapine, quetiapine, risperidone) have a weak anticholinergic action and produce fewer extrapyramidal side effects compared to conventional antipsychotics; however, these drugs, when used for an extended period, may be associated with an increased risk of hyperglycaemia and mortality from any cause. In addition, they can increase the risk of stroke in elderly patients who have dementia-related psychosis. If used, antipsychotics must be administered in low doses and for a short time, while antiepileptics, in particular valproate, can be useful in the control of sudden attacks of aggression. Finally, sedatives (for example, short-acting benzodiazepines) are sometimes used for a short period of time to relieve anxiety related to specific events but are not recommended for long-term therapy [29,30].
As previously mentioned, the detailed anamnesis, serological laboratory tests, physical and neurological tests, electromyography, electroencephalogram and MRI or PET represent the first and second level diagnostic tests in the hypotheses of suspected dementia (genetic tests to be performed, which represent the third level of investigation). The clinical picture is completed by the psychological interview and the administration of a battery of neuropsychological tests calibrated on the patient (for example, the Mini-Mental Status Examination or the Montreal Cognitive Assessment), to best facilitate the exact diagnosis. In terms of dementia and impaired cognitive, for example, it is essential that the symptomatology involves two or more specific domains: a) impaired ability to acquire and remember new information (for example, to ask repetitive questions, often to put objects that are not in their place or to forget appointments); b) impaired reasoning and management of complex activities and poor judgment (for example, being unable to manage a bank account, making poor financial decisions); c) language dysfunction (for example, difficulty thinking common words, pronunciation and/or writing errors); d) visuospatial dysfunction (for example, the inability to recognize common faces or objects); e) changes in personality, attitude, or behavior .
Medical science is still a long way from discovering the pharmacological and genetic mechanisms that can block these pathologies and the challenge for the future will be to direct research in this direction. We still die of these diseases and the quality of life, especially in the last years of life, is strongly compressed in the negative. It must be a common commitment of all neuroscientific researchers to find solutions that are able to stem these morbid conditions, which destroy not only the patient but also the family members and those who care for them.
© 2020 Giulio Perrotta. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.