DEMENCIA

Memory impairment is often prominent as an early symptom. Patients may experience difficulty learning new material or remembering recent conversations or events, and they may misplace valuables, such as keys, or forget to turn off the stove. In more severe dementia, patients also forget previously learned material, including the names of loved ones. Disturbances in spatial abilities, expressive or receptive language, and executive functions.

To receive a diagnosis of dementia a patient must have cognitive deficits that are sufficiently severe to cause impairment in daily functioning and that represent a change from a previous level of functioning.

The prevalence rate of Creutzfeldt-Jakob disease (CJD) for example, is 1 in 1 million. Although rare CJD generates interest because of media attention to the bovine spongiform encephalopathy, or " mad cow".

Alzheimer´s disease is a neurodegenerative disorder characterized by progressive cognitive decline and a broad spectrum of brain pathology, including accumulation of fibrillar amyloid-B protein in plaques and vessels, neurofibrillary tangles, and synaptic and neuronal loss.

In contrast, dementia caused by cerebrovascular disease is often associated with an abrupt onset.

The term vascular dementia (VaD) actually comprises several heterogeneous syndromes, including cortical ( multiinfarct) demetia and noninfarct vascular demetia. And because evidence suggests that small stokes or risk factors for vascular disease may lead to increased clinical expression of AD. Comorbility of AD and VaD is especially common in the very old.
----------------------------------------------------------------------------------------------------------------------

In AD, plaques develop in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are used in thinking and making decisions.

In a cross-sectional study of 48 AD patients without diabetes, 20 cognitively normal diabetic patients, 16 patients with frontotemporal dementia, and 84 cognitively normal controls, researchers found that dysfunctionally phosphorylated insulin receptor substrate-1 (IRS-1), a neuronal protein, is detectable in blood using exosome-based technology and may be able to predict AD up to 10 years before the appearance of symptoms.

Compared with all other groups, patients with AD had several-fold higher p-Ser312-IRS-1 and Ser312/p-panY ratios and lower p-panY-IRS-1

Mild Alzheimer disease

Signs of mild AD can include the following:

• Memory loss
• Confusion about the location of familiar places
• Taking longer to accomplish normal, daily tasks
• Trouble handling money and paying bills
• Compromised judgment, often leading to bad decisions
• Loss of spontaneity and sense of initiative
• Mood and personality changes; increased anxiety
  
  
  
  

  Moderate Alzheimer disease

  The symptoms of this stage can include the following:

  • Increasing memory loss and confusion
  • Shortened attention span
  • Problems recognizing friends and family members
  • Difficulty with language; problems with reading, writing, working with numbers
  • Difficulty organizing thoughts and thinking logically
  • Inability to learn new things or to cope with new or unexpected situations
  • Restlessness, agitation, anxiety, tearfulness, wandering, especially in the late afternoon or at night
  • Repetitive statements or movement; occasional muscle twitches
  • Hallucinations, delusions, suspiciousness or paranoia, irritability
  • Loss of impulse control: Shown through behavior such as undressing at inappropriate times or places or vulgar language
  • Perceptual-motor problems: Such as trouble getting out of a chair or setting the table

Severe Alzheimer disease

Patients with severe AD cannot recognize family or loved ones and cannot communicate in any way. They are completely dependent on others for care, and all sense of self seems to vanish.

Other symptoms of severe AD can include the following:

• Weight loss
• Seizures, skin infections, difficulty swallowing
• Groaning, moaning, or grunting
• Increased sleeping
• Lack of bladder and bowel control

In end-stage AD, patients may be in bed much or all of the time. Death is often the result of other illnesses, frequently aspiration pneumonia.

Diagnosis

Means of diagnosing AD include the following:

• Clinical examination: The clinical diagnosis of AD is usually made during the mild stage of the disease, using the above-listed signs
• Lumbar puncture: levels of tau and phosphorylated tau in the cerebrospinal fluid are often elevated in AD, whereas amyloid levels are usually low; at present, however, routine measurement of CSF tau and amyloid is not recommended except in research settings
• Imaging studies: Imaging studies are particularly important for ruling out potentially treatable causes of progressive cognitive decline, such as chronic subdural hematoma or normal-pressure hydrocephalus
  
  

  Blood Studies

  Laboratory tests can be performed to rule out other conditions that may cause cognitive impairment. Current recommendations from the American Academy of Neurology (AAN) include measurement of the cobalamin (vitamin B12) level and a thyroid function screening test. 

  There is a possible link between vitamin D deficiency and cognitive impairment.However, vitamin D deficiency has not been identified as a reversible cause of dementia.
  
  

  

  

  

  

  

  
  

  

  
  

  

  
  

  Pathophysiology

  

  

  
  

  

  
  

  

  
  

  

  
  

  

  
  

  

  

  

  

  
  

  

  

  

  

  
  

Dementia with Lewy bodies

Recent findings indicate that the presence of visual hallucinations and agnosia in the course of a dementing illness can help distinguish DLB from AD.

Pick´s disease and other frontal lobe dementias are fairly rare and are characterized in their early stages by changes in personality, executive dysfunction, deterioration of social skills, emotional blunting, behavioral desinhibition, and language abnormalities. 

Structural brain imaging of patients with Pick´s disease typically reveals prominent frontal or temporal atrophy or both, with relative sparing of the parietal and occipital lobes. The diagnosis is confirmed by autopsy finding of Pick inclusion bodies.

Normal pressure hydrocephalus (NPH), also known as non obstructive or communicating hydrocephalus, is somewhat of a misnomer, falsely suggesting that intracranial pressure  is always normal in this condition when in fact there can be elevation in ICP. 

NPH is associated with a classic triad of dementia, gait disturbance, and urinary incontinence.

The most common form of substance-induced persisting dementia is caused by alcohol. The Wernicke-Korsakoff syndrome  consists of two phases. The first is a potentially reversible Wernicke encephalopathy characterized by a confused state, gait ataxia, and eye movement abnormalities. <If left untreated with large doses of thiamine, a chronic Korsakoff state follows, characterized by severe anterograde and retrograde amnesia, and executive deficits, apathy, and disinterest in alcohol. Wernicke-Korsakoff syndrome usually arises in a context of persistent alcohol abuse and poor nutrition.

Memory impairment is a hallmark of dementia and is required to make a diagnosis. Dementia is distinguished from amnestic disorder by the involvement of additional cognitive deficits ( e.g.. language, visuospatial processing, problem solving). Although dementia and delirium both include global cognitive impairment, delirium is characterized by prominent deficits in attention and awareness of the environment , and the symptoms typically develop rapidly and fluctuate in severity. Dementia often co-occurs with depression or depressive symptoms, but depression alone can cause significant cognitive impairment that is difficult to distinguish from dementia.