Space-occupying lesions, such as intracranial tumors with an indolent course (e.g., meningioma, low-grade glioma, lymphoma), subacute/chronic subdural hematomas, and slow-growing intracranial abscess/empyema, may present with progressive neuropsychiatric changes, especially when they affect frontal, temporal, parietal, callosal, or caudate locations. Cognitive and psychiatric manifestations may include apathy, emotional lability, irritability, forgetfulness, inappropriate behavioral and personality changes, as well as disturbance of more specific higher-order cognitive functions. Such progressive clinical picture may lead to a dementia diagnosis. However, only a few lesions present as isolated dementia, and most cases have other focal neurological signs and, rarely, intracranial pressure manifestations, differentiating them from degenerative dementia [14]. Neurosurgical excision and adjuvant treatments of these mass lesions can produce reversibility of the symptoms.

Hydrocephalus refers to a condition of pathologically enlarged ventricular size related to disorders with or without obstruction to CSF absorption, stated as obstructive and nonobstructive hydrocephalus, respectively. Obstructive hydrocephalus is further categorized into communicant and noncommunicant hydrocephalus, depending if there is a structural blockage of the CSF circulation within the ventricular system in the latter case. Regardless of the underlying cause and its clinical course, the clinical picture produced by hydrocephalus should be always regarded as a potentially reversible condition, upon prompt procedures of CSF derivation. Normal pressure hydrocephalus denotes a particular syndrome characterized by radiographic ventriculomegaly out of proportion to any sulcus enlargement, excluding hydrocephalus ex vacuo due to loss of adjacent brain parenchyma in degenerative processes (not thought of as hydrocephalus in its strict sense), combined with normal opening pressures on lumbar puncture, excluding hypertensive hydrocephalus which is usually due to an identifiable cause. It consists of a nonspecific clinical triad of gait and balance disturbance (common descriptors include “wide-based,” “shuffling,” “magnetic,” “apraxic,” “petit pas” gait), subcortical dementia (including executive dysfunction, behavioral or personality changes, immediate and delayed memory impairment), and urinary incontinence (preceded long before by urinary frequency and urgency). Normal pressure hydrocephalus is considered symptomatic or secondary if, for instance, a prior head trauma, subarachnoid hemorrhage, meningitis, neurosurgery, mass lesions, or aqueduct stenosis is identified. Those without a recognizable insult are called idiopathic normal pressure hydrocephalus (INPH). This entity typically manifests during adult life, frequently after 60 years old, as an insidiously progressive, chronic disorder. It is considered as a classical potentially reversible cause of dementia, because CSF shunting procedures can lead to significant clinical improvement, especially at early stages. Indeed, misdiagnosis and delayed recognition are two important causes of poor responsiveness to treatment in INPH. On the other hand, regarding the serious potential complications associated with ventriculoperitoneal shunts, the treatment of INPH should not be considered lightly. There is little consensus concerning the diagnosis of INPH and the selection of patients for shunt placement. Documentation of ventricular enlargement by brain imaging must be interpreted in conjunction with the clinical history and neurological examination, to differentiate it from other disorders. Many disorders may resemble or occur in combination with INPH, such as vascular dementia, neurodegenerative disorders (Alzheimer’s disease, progressive supranuclear palsy, Parkinson’s disease, Lewy body disease), primary urological disorders, and spondylotic myelopathy, leading to misdiagnosis and resulting in poor shunting outcome. In order to avoid potential complications and increase the certainty of a positive shunt response, many tests are applied in clinical practice, but no single test has been validated to rule out potential response to surgery. The recommended supplemental evaluation includes, in order of increasing sensitivity/positive predictive value (but also invasiveness), a 40–50-ml tap test, measurement of the CSF outflow resistance via an infusion test, and prolonged external lumbar drainage. False-positive diagnosis may also result from treatment of secondary causes of normal pressure hydrocephalus, often with a favorable response to shunt placement. Currently, ventricular shunting is the only recognized treatment for INPH. An early and accurate diagnosis, leading to a prompt surgical treatment, may produce a dramatic clinical improvement, mainly of gait and urological dysfunction but also of the cognitive decline, but, sometimes, only a mild and transient recovery of cognition, and even gait disorder, has been seen [25–28].

Traumatic brain injury (TBI) is commonly associated with neurocognitive problems, which may potentially improve over time and under comprehensive rehabilitation programs.

Short–term cognitive impairment refers to the immediate post-injury neurobehavioral changes, mostly characterized by a variable duration of loss of consciousness and posttraumatic amnesia, combined with different degrees of disorientation and confusion, features that are used to define the severity of TBI between mild, moderate, and severe cases. Patients may also experience an acute confusional status, manifested by gross fluctuations of cognitive and behavioral symptoms and impaired sleep–wake cycle with increased daytime somnolence alternating with agitation, affective lability, and perceptual disturbance. Additionally, focal neurological signs related to focal injuries (e.g., penetrating brain lesions, brain contusions, and intracranial hematomas) and other manifestations depending on immediate complications (e.g., hydrocephalus, seizures, meningitis, vascular injury, multiple organ failure, and polytrauma) may also be apparent. The recovery process after TBI is dependent upon the level of the injury severity. In general, cognitive deficits associated with mild TBI resolve fully within 3–6 months, contrasting with patients with moderate and severe TBI, whom often recover slowly and frequently do not return to their preinjury cognitive level. Attempts to define patient’s prognosis after TBI remain difficult and complex. Each recovery is an individualized process that depends on many factors, such as premorbid context (age, premorbid health status, prior intellectual functioning, and psychiatric comorbidities), the actual brain injury (its nature, interval from injury to initial treatment, acute interventions, and posttraumatic amnesia duration), and post-acute setting (rehabilitation and social support). Long-term cognitive impairment refers to the persistent neurocognitive disorder that varies in terms of their severity and chronicity. Approximately 15 % of patients with mild TBI present with persistent problems, including cognitive deficits (i.e., memory impairment, reduced concentration, and delayed information processing), in addition to physical complaints (i.e., headache, dizziness, and other cranial nerve symptoms) and emotional and neurovegetative problems (i.e., anxiety, irritability, depression, insomnia, change in appetite, decreased libido, fatigue, personality change), so-called post-concussion syndrome. A higher proportion of patients, nearly 65 %, with moderate to severe TBI exhibit cognitive sequela involving a diversity of deficits, such as difficulties in general intelligence, episodic and working memory, executive functions, attention, information-processing speed, language functions, and visuospatial processing, often resulting in long-lasting disability [29, 30]. Nonetheless, it should be stressed that the potential of recovery in TBI is high and cognitive interventions and training should be considered even years after the trauma.

On the other hand, TBI may also be associated with irreversible conditions characterized by delayed progressive cognitive impairment and dementia. It has been recognized that traumatic brain injury is a risk factor for late-life dementia. Indeed, multiple epidemiologic studies have shown that patients experiencing moderate to severe TBI in early to midlife have an increased risk for dementia between two- and fourfold, compared with the general population. Still, it has long been well known that patients with multiple TBIs, as experienced by professional boxers and other athletes in contact sports, are associated with a high risk of chronic traumatic encephalopathy, a distinctive clinical and pathological dementia. Previously known as dementia pugilistica, this progressive neurological syndrome may develop many years after repeated insults. The clinical picture ranges from mild symptoms of dysarthria, pyramidal signs, and disequilibrium to severe disability with parkinsonian symptoms, such as tremor, rigidity, and masked face, combined with neuropsychiatric manifestations and ataxia and, at late stages, dementia [31].

Dural arteriovenous fistula is a rare but potentially reversible neurological condition, resulting from acquired lesions consisting of an abnormal direct communication between cerebral arterial vasculature and dural sinus lumen. Common initial symptoms include pulsatile tinnitus, headache, visual disturbances, as well as neurological signs due to acute intracranial hemorrhage. In addition to the more usual presentations, cases resembling neurodegenerative conditions, characterized by encephalopathy or cognitive decline with insidious onset or stepwise course, and even progressive parkinsonian disorders, have been reported. Brain MRI may show diffuse white matter changes and abnormal pattern of flow voids. MRI angiography, but mostly conventional angiography, confirms the arteriovenous shunt and its anatomy. Selective embolization results in complete or near-complete resolution of neurological function, which includes “reversible dementia” [32–34].

Cognitive impairment induced by medications is one of the main causes of “reversible dementia,” especially in elderly due to low hepatic and renal functions, increase fat to lean body ratio, polypharmacy, and more likelihood of premorbid brain pathology. Medication classes more frequently causing cognitive and/or psychiatric symptoms are hypnotics and sedatives like benzodiazepines, anticholinergics (scopolamine, trihexyphenidyl, benztropine, and other medications with significant anticholinergic properties), antiepileptics (mainly phenobarbital, primidone, and topiramate, but also valproate, zonisamide, carbamazepine, and phenytoin), tricyclic antidepressants, dopaminergic agents (in descendent order: anticholinergic, amantadine, dopamine agonists, monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, and levodopa), antihistamines, antipsychotics, lithium, opioids, amphetamines, steroids, digoxin, and beta-blockers. The association of several of these drugs by one patient increases the risk of neuropsychiatric side effects. Short duration of symptoms, history of polypharmacy, and temporal relationship between neuropsychiatric symptoms and drug changes may help the diagnosis. Discontinuation of drugs should improve mental status [35].

Alcohol abuse can cause cognitive impairment, indirectly due to nutritional deficiencies and metabolic abnormalities, but also due to alcohol-related dementias, namely, Marchiafava–Bignami disease and the “alcoholic dementia.” Marchiafava–Bignami disease is seen, mainly, in chronic severe alcoholics and refers to selective demyelination of the corpus callosum of unknown pathophysiology. Heterogeneous neurological presentations have been described, including confusion, psychomotor slowing, behavioral changes, and a rapidly progressive dementia in some patients. Brain MRI may show hyperintensity in T2-weighted images and restriction in diffusion-weighted imaging (DWI) affecting, mainly, the middle part of corpus callosum, subcortical white matter, and cerebellar peduncles. While most patients have a progressive illness, some stabilize, and others may even exhibit some improvement with adequate nutrition and thiamine replacement. Alcoholic dementia is an ill-defined entity that probably comprises different disorders more commonly found in chronic alcoholic patients like Wernicke–Korsakoff syndrome, pellagra, Marchiafava–Bignami disease, hepatic encephalopathy, head injury, subdural hematoma, vascular cognitive impairment, etc. Alcohol rehabilitation aiming abstinence is the key for its prevention [36].

Chronic exposure to heavy metals (such as mercury, lead, arsenic, aluminum, manganese, tin, bismuth, and thallium) and organic chemical s (e.g., industrial solvents toluene, hexacarbon, hydrocarbons) may result in cognitive and behavioral impairment, besides other neurological and systemic manifestations. Clinical history should include occupational contact because, although mental changes are most often not reversible, identification of the offending agent may prevent further decline [37].

Carbon monoxide poisoning and, less often, other hypoxia circumstances (e.g., cardiopulmonary arrest, complications of surgery and anesthesia, shock, and respiratory depression from opioids, barbiturates, or benzodiazepine overdose) may develop a delayed post-hypoxic leukoencephalopathy. This is a rare disorder where patients, following a complete or near-complete recovery from any event that causes a period of prolonged cerebral hypo-oxygenation, present with an indolent subacute worsening of neuropsychiatric symptoms days to weeks later. The clinical picture may show a psychomotor retardation, cognitive dysfunction, personality change with bizarre behavior, bladder and bowel incontinence, parkinsonism and other movement disorders, pyramidal signs, and akinetic mutism. Neuroimaging typically discloses diffuse and confluent subcortical white matter signal abnormalities. Supportive care and neurorehabilitation are the essence of treatment, since there is no known effective therapy. Prognosis is variable, but the majority of patients who survive the rehospitalization period demonstrate a full or near-full recovery within 1 year [38, 39].

Radiation-induced late-delayed encephalopathy may occur several months to years after brain irradiation due to brain neoplastic lesions or prophylaxis of tumor dissemination to brain. Progressive dementia, mainly of a subcortical type, behavioral changes, ataxia, and urinary incontinence may be seen. Manifestations of the delayed effects of radiotherapy are related to patient age, amount of radiation (both volume and doses), fraction sizes, and timing of chemotherapy. Therefore, although the established radiation encephalopathy is not a reversible condition, an accurate planning of radiation targeting and dosing may prevent the development of neurobehavioral sequelae in some patients [40].

Cobalamin deficiency may occur in pernicious anemia, loss of gastric acid, gastric and ileal resection, blind loop syndrome, abuse of nitrous oxide, strict vegans, and alcoholics. Neuropsychiatric symptoms are common, consisting in cognitive impairment and psychiatric manifestations such as depression, mania, anxiety, insomnia, and psychosis. Neuropsychiatric complications can occur in the absence of macrocytic anemia or other neurological manifestations (like subacute combined degeneration, sensory polyneuropathy, and optic atrophy). Neurological symptoms of cobalamin deficiency need to be treated with supplementation as early as possible for the best results [41]. Folate deficiency (vitamin B9) may produce the same hematological manifestations, myelopathy and polyneuropathy, as those seen in cobalamin deficiency; however, overt encephalopathy symptoms are rare, probably owing to alternative cellular mechanisms available to preserve methionine methylation in folate deficiency [41]. Progressive dementia caused by cobalamin and folate deficiency is a more controversial issue, because several studies have shown that reversibility of cognitive symptoms after vitamin replacement is very rare, especially in patients who fit the diagnostic criteria for Alzheimer’s disease [42, 43]. Moreover, there is a high incidence of low levels of cobalamin and folate in the elderly population and also in patients with Alzheimer’s disease, comparing with normal controls, suggesting a concurrent deficiency rather than a causal association [43–45].

Thiamine deficiency can occur whenever there is disequilibrium between inadequate nutrition to the metabolic demand, such as excessive alcohol use, hiperemesis gravidarum, elderly, systemic consumptive disease, and anorexia nervosa. Reversible cognitive impairment, mainly disorientation, attention deficit, memory loss, and apathy, can be observed as part of Wernicke’s encephalopathy, sometimes accompanied by axial ataxia and mesencephalic–hypothalamic dysfunction, typically presented with ophthalmoplegia, pupillary light-near dissociation, and dysautonomia. Diagnosis is made by clinical presentation in the appropriate clinical context, while thiamine levels in serum did not reflect the correct levels in tissue and cannot confirm or refute the diagnosis. Brain MRI may help the diagnosis, by demonstrating T2/FLAIR hyperintensity of the mammillary bodies, periaqueductal gray matter, colliculi, and thalamus and by excluding alternative causes. Korsakoff syndrome is an amnestic syndrome, which becomes apparent after improvement of the encephalopathic expression, and may result from recurrent episodes or inappropriate recovery of acute encephalopathy. It is typically poor responsive to treatment, representing, mostly, an irreversible phase of thiamine dementia [41].

Niacin deficiency, or pellagra, can have a cognitive impairment very similar to Wernicke’s encephalopathy, sometimes associated with other neurological symptoms (sensorimotor polyneuropathy, dorsal column involvement in the spinal cord, pyramidal signs, startle response) and other extra-neurological symptoms, i.e., gastrointestinal and dermatologic features. In patients with Wernicke’s-like encephalopathy, who are not improving with thiamine replacement, a trial with nicotinic acid supplements should be pursued [41].

Electrolyte disorders, particularly, sodium, calcium, and magnesium, may result in transient impairment in mental status resembling dementia, which classically resolve after correction of the underlying abnormality. Hyponatremia and hypernatremia patients demonstrate malaise, lethargy, fatigue, confusion, irritability, sleep disturbance, muscle cramps, and headache that could evolve to a serious condition with nausea, vomiting, focal signs, tremor and myoclonus, seizures, and coma [36]. Calcium disturbances can also cause neuropsychiatric manifestations. Besides neurocognitive dysfunction, psychiatric symptoms (such as emotional lability, depression, psychosis, and anxiety) and decreased consciousness, hypocalcemia can present also with increased excitability in peripheral and central nervous system, with perioral and distal paresthesia, muscle cramps and spasms, tetanus, and seizures. In chronic hypocalcemia, in addition to cognitive impairment, there may be parkinsonism, chorea, myelopathic changes, and intracranial hypertension, with brain imaging showing calcification of the basal ganglia. Hypercalcemia can present with generalized weakness, confusion, apathy, agitation, depression, mania, lethargy, and, in severe cases, coma [36]. Hypomagnesemia is often concomitant with hypocalcemia, and the clinical presentation is very similar. Hypermagnesemia is less common and presents with somnolence, confusion, neuromuscular weakness, hypotension and respiratory depression, and in severe cases coma [36].

Endocrine disorders, mostly, thyroid, parathyroid, and cortisol dysfunction, and hypoglycemia can cause neuropsychiatric symptoms. Hypothyroidism can manifest with mental changes, including apathy, somnolence, and concentration impairment resembling depression, eventually evolving to confusion, delirium, lethargy, and psychosis, usually accompanied by systemic symptoms (i.e., fatigue, cold intolerance, dry skin, and weight gain). Treatment of the underlying cause and thyroid hormone replacement should be promptly warranted. However, the evidence that hypothyroidism causes progressive dementia and that cognitive impairment is reversible upon thyroid supplementation is a controversial matter [46–48]. Hyperthyroidism can produce a myriad of cognitive and psychiatric symptoms such as memory and concentration impairment, attention and planning deficit, restlessness, irritability and anxiety, and, in the elderly, depression and lethargy [49]. Besides neuropsychiatric symptoms, other neurological and extra-neurological manifestations may be patent, helping the diagnosis: tachycardia, tremor, hyperreflexia, seizures, chorea, proximal myopathy, thyrotoxic periodic paralysis, peripheral neuropathy, and dysthyroid orbitopathy.

Hypercortisolism (Cushing syndrome) is characterized by cognitive dysfunction, mainly memory impairment, but may also affect other cognitive domains (attention, reasoning, comprehension, and information processing), associated with psychiatric symptoms, such as anxiety, insomnia, depression, dysphoria, mania, and psychosis, in addition to the systemic manifestations (i.e., trunk obesity, hypertension, hirsutism, acne, osteoporosis, hyperglycemia, menstrual irregularities, proximal weakness of lower limbs). Adrenal insufficiency (including Addison disease in primary adrenal insufficiency) includes abnormalities in glucocorticoids, aldosterone, and androgens and, in a chronic setting, can cause cognitive impairment, depression, and psychosis. Moreover, some systemic symptoms related to adrenal insufficiency, such as generalized weakness, fatigue, asthenia, anorexia, and weight loss, may resemble a psychiatric condition. The diagnosis is established by cortisol levels and serum adrenocorticotropic hormone (ACTH), excluding exogenous supplementation of glucocorticoids and localizing the dysfunction along the hypothalamic–pituitary–adrenal axis. Treatment lies on the underlying cause and, in adrenal insufficiency, hormones replacement. Patients may improve with treatment, but often, neuropsychiatric symptoms do not fully reverse [50].

Hypoglycemia has been related to persistent neuropsychiatric symptoms. Chronic hypoglycemia, principally in the context of insulin-secreting tumor or a tight glycemic control by a diabetic, is a rare syndrome characterized by insidious change in personality, memory, and behavior that could be misdiagnosed as dementia. Improvement is not achieved with glucose supplementation, but can occur after removal of the excessive insulin, frequently as a slow and protracted recovery for several months [36]. Furthermore, recurrent episodes of severe hypoglycemic episodes have been associated with an increased risk of subsequent dementia in older patients with type II diabetes mellitus [51].

Wilson disease is a rare, autosomal recessive disorder of copper transport. It is a systemic condition that usually begins in adolescence and typically comprises liver failure and neurological manifestations, beyond many other organ involvement (hemolytic anemia, joint and bone changes, hyperpigmentation, azure blue nails, nephrolithiasis, cardiomyopathy, sunflower cataracts). Neurological manifestations include dysarthria and a wide spectrum of movement disorders, dystonia, parkinsonism, tremor, ataxia, and intentional tremor; neuropsychiatric symptoms consist of, mainly, frontal lobe and subcortical cognitive impairment and behavioral symptoms characterized by change in personality, disinhibition, and emotional lability. Most patients with neurological dysfunction also have Kayser–Fleischer rings on slit-lamp ophthalmologic examination. The brain MRI may show some changes, but the diagnosis is almost confirmed by biochemical abnormalities, i.e., low serum ceruloplasmin and high level of 24-h urine cooper. The treatment, consisting of chelating cooper, can prevent severe neurologic symptoms [50].

Porphyrias are a rare heterogeneous group of inheritable disorders that result from abnormalities in heme biosynthesis. Of particular interest to the neurologist and psychiatrist are three acute neuropsychiatric porphyrias: acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria. The acute attack is usually accompanied by neurovisceral symptoms: abdominal pain, encephalopathy and psychiatric symptoms (psychosis, anxiety, and confusion), peripheral neuropathy (usually motor neuropathy and preferentially affecting proximal muscles, but also sensory and cranial neuropathies), autonomic features (tachycardia, constipation or diarrhea, vomiting, and gastroparesis), seizures, and, also, in the last two porphyrias, skin lesions on sun exposure surfaces. Diagnosis is made by quantitative measurement of both porphobilinogen and aminolevulinic acid on a urine sample and then a detailed analysis of urine and stool samples to differentiate between the disorders. Treatment of acute attacks involves supportive therapy and specific treatment with intravenous heme arginate. Long-term management of these patients is focused on prevention of acute attacks through avoidance of porphyrinogenic drugs and heme arginate prophylaxis [52].

Cerebrotendinous xanthomatosis is a rare inborn error of bile acid metabolism that manifests as a progressive neuropsychiatric dysfunction characterized by cognitive impairment leading to a pattern of frontotemporal dementia, psychiatric symptoms, cerebellar ataxia, myelopathy, peripheral neuropathy, movement disorders, and seizures. Other systemic manifestations may also be present, assisting the diagnosis, namely, early-onset cataracts, tendon xanthomata, and gastrointestinal symptoms such as diarrhea. The nonspecific cognitive and behavioral manifestations can be the earliest symptoms, which are often unrecognized, precluding a prompt diagnosis. Brain MRI may show, in the majority of patients, some changes, the most common being hyperintense lesions on T2-weighted images in the dentate nucleus, but the diagnosis is made by biochemical abnormalities, lying on elevated serum cholestanol and an increased urinary excretion of bile acids. Treatment with chenodeoxycholic acid inhibits defective bile acid synthesis and reduces elevated plasma and hepatic concentrations of cholestanol and bile alcohols, halting disease progression or even reverse of some dysfunction [53].

Niemann–Pick disease type C is a rare, autosomal recessive lysosomal lipid storage disorder, characterized by progressive neurovisceral symptoms. The clinical spectrum ranges from a cholestatic jaundice in the neonatal period, or infantile hepatosplenomegaly and developmental delay, to an adult-onset chronic neurodegenerative disease. The adult form includes several neurological manifestations (mainly vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, and dysphagia, but also cataplexy, seizures, and dystonia), associated with a progressive cognitive decline leading to dementia, frequently accompanied or preceded by nonspecific and atypical psychiatric disturbances (schizophrenia-like psychosis, affective disorders, obsessive–compulsive behavior, sleep disorders, hyperactivity, agitation, aggressiveness, or self-mutilations). Systemic signs are inconstant and, usually, asymptomatic. The diagnosis is established with filipin test on a fibroblast culture from a skin biopsy, confirmed by sequencing of the NPC1 and NPC2 genes. Treatment of progressive neurological manifestations lies on a recent disease-specific drug, miglustat, which improves the disease evolution [54, 55]. Few other lysosomal storage disorders, manifested with intellectual impairment in the infancy/childhood or other neurological symptoms, specifically Gaucher’s disease, mucopolysaccharidosis type I and II and Fabry disease, have now a specific treatment available with enzyme replacement therapy, which improves some features of the illness. Unfortunately, the effectiveness of these disease-modifying therapies on neurocognitive aspects is still a matter of uncertainty [56–58].

Most central nervous system (CNS) infections present with an acute change in mental status, but some develop more insidiously, mimicking a neurodegenerative dementia.

Human immunodeficiency virus (HIV) disease can cause cognitive impairment as a result of primary HIV disease, opportunist infectious and malignancies, toxic effect of medication, and depression, due to psychosocial consequences associated with HIV infection. HIV-associated neurocognitive disorders (HAND) are characterized by a triad of cognitive impairment, behavioral changes, and motor dysfunction [59]. Cognitive impairment can result in mental slowness, problem-solving and decision-making difficulties, perseveration, and impairment of attention, memory, and/or learning [60]. Apathy and social withdrawal are neuropsychiatric manifestations that may occur and resemble depression. A progressive and disabling impairment in motor function can also ensue, including hyperreflexia, hypertonia, ataxia, tremor, bradykinesia, and postural instability [59]. Diagnosis is based in the clinical features, brain MRI and CSF, to exclude other opportunist complications. Several categories of HAND can be established, depending on interference in everyday functioning: asymptomatic neurocognitive impairment, mild neurocognitive impairment, and HIV-associated dementia (HAD). In patients treated with combination antiretroviral therapy (cART), intellectual impairment is attenuated and the temporal course prolonged, and, therefore, HAD has been less common despite a high frequency of milder stages of HAND [61]. Early recognition and management of HIV infection with cART to suppress the HIV viral load may effectively limit, or even improve, neurocognitive impairment [62]. Additional supportive therapies should be used to control other neuropsychiatric symptoms. In the context of HIV infection and cognitive impairment, opportunistic CNS neoplasms and infections should be actively investigated because they have specific treatments that could successfully halt or improve the intellectual decline, such as CNS lymphoma, progressive multifocal leukoencephalopathy due to JC virus reactivation, cryptococcal meningitis, toxoplasmosis, and cytomegalovirus and varicella-zoster virus encephalitis.