Dementia, Testing and Pathology Section

In this section we will look at the methods and techniques available for the assessment of dementias, many of which have been known for many years. As there is no cure available for dementias, these techniques can only be used to qualify the condition progress on an on-going basis, enable pharmaceutical companies evaluation in longitudinal studies on new drugs or neurological studies of brain chemistry. The majority of effort has been directed towards Alzheimer’s disease. Diagnosis of probable Alzheimer’s requires the presence of dementia symptoms characterized by a history of progressive memory loss and decline in one or more other areas of cognition that is sufficient to interfere with everyday functioning, documentation of the cognitive impairment with psychometric testing, and the exclusion of alternative explanations for the dementia syndrome.

On the basis of prospective longitudinal clinical/pathological studies performed primarily in centres specializing in memory disorders, the clinical diagnosis of Alzheimer’s has a positive predictive value of around 80%. Data from com¬munity-based studies often report a lower figure. This is be¬cause clinical diagnostic accuracy often is confounded when the core symptoms of Alzheimer’s are shared by other pathologically distinct neurodegenerative dementias. In addition, cognitive impairment may be difficult to assess reliably in certain individuals for a variety of reasons. Because most dementing illnesses impair insight, clinicians usually must obtain additional information from someone who knows the individual well. The combination of these factors may delay a patient's evaluation and present difficulties establishing a correct diagnosis during the earliest symptomatic stage of the illness. The development of new therapies for Alzheimer’s, particularly those that target the core pathologic features, increases the need to improve diagnostic accuracy and efficiency, particularly during the earliest phase when attempts to halt or slow the progression are most appropriate.

Mental Status Tests

The clinical examination provides data to fulfil inclusionary and exclusionary criteria for the diagnosis of dementia and to document symptoms such as delusions or depression that identify certain subgroups of patients.Mental status testing, an essential component of the clinical examination, includes specific assessment of orientation, registration, attention, calculation, recent recall, naming, repeating, understanding, reading, writing, and ability to draw or copy. Because cognitive impairment may occur in depression, it is important to inquire about affective state and depressive symptoms, such as disturbed sleep and weight loss, before diagnosing Alzheimer’s disease for example. Quantitative aids to the clinical examination include the Mini-Mental State Examination for cognitive screening; the Blessed Dementia Scale for clinical symptoms and social function; the Clinical Dementia Rating for cognitive screening; the Hamilton Depression Scale for severity of depression; the Present State Examination for anxiety, depression, delusions, and hallucinations; and the Hachinski Scale for estimating the likelihood of multi-infarct dementia. Complete examination of sensory and motor systems (including cranial nerves, tone, reflexes, coordination, gait, and sense of limb positioning) is needed to exclude other neurologic disorders. In early stages, patients are alert and free of neurologic changes related to the dementia except for the occasional presence of pouting, jaw jerk reflex, rigidity, or twitching, all of which may be encountered in nondemented elderly people anyway. As the disease progresses, some patients become apathetic or show irritability, agitation, paranoid ideas, sleep disorders, or incontinence. In the very advanced stages, patients may become mute and lose all ability to communicate.

One in three individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have a cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. Up to 64% of persons who have experienced a stroke have some degree of cognitive impairment, with up to a third developing dementia. Conversely, postmortem pathological studies indicate that up to 34% of dementia cases show significant vascular pathology.

The Mini Mental State Examination (MMSE) is a commonly used set of questions for screening cognitive function. This examination is not suitable for making a diagnosis but can be used to indicate the presence of cognitive impairment, such as in a person with suspected dementia or the result of a head injury. The MMSE is far more sensitive in detecting cognitive impairment than the use of informal questioning or overall impression of a patient's orientation.
    • The test takes only about 10 minutes but is limited because it will not detect subtle memory losses, particularly in well-educated patients
    • In interpreting test scores, allowance may have to be made for education and ethnicity
    • The MMSE provides measures of orientation, registration (immediate memory), short-term memory (but not long-term memory) as well as     language functioning.
    • The examination has been validated in a number of populations. Scores of 25-30 out of 30 are considered normal; the National Institute     for Health and Care Excellence (NICE) classifies 21-24 as mild, 10-20 as moderate and les than 10 as severe impairment. The MMSE     may not be an appropriate assessment if the patient has learning, linguistic/communication or other disabilities
The MMSE test is shown in HERE as the full version. In practice a family doctor for an initial examination may well curtail the set of questions and substitute alternatives. Asking to draw a clock face with the hands at 10 to 11 is a usual favourite.

The Blessed Dementia Scale (DS) was developed in 1968 by Blessed and colleagues in an attempt to quantify the “degree of intellectual and personality deterioration” in the elderly. Personality changes are scored 1 if present or 0 if absent. The form is shown HERE

The NINCDS-ADRDA Alzheimer's Criteria were proposed in 1984 by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association) and are among the most used in the diagnosis of Alzheimer's disease. These criteria require that the presence of cognitive impairment and suspected dementia to be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable Alzheimer’s; whilst they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They also specify eight cognitive domains that may be impaired in Alzheimer's. These criteria (below) have shown good reliability and validity. At the same time, advances in functional neuroimaging techniques, such as PET or SPECT (see Later), have already proven their utility to differentiate Alzheimer's disease from other possible causes and have led to proposals of revision of the NINCDS-ADRDA criteria that take into account these techniques.
    Definite Alzheimer's disease: The patient meets the criteria for probable Alzheimer's disease and has histopathologic evidence of     Alzheimer's via autopsy or biopsy.
    Probable Alzheimer's disease: Dementia has been established by clinical and neuropsychological examination. Cognitive impairments     also have to be progressive and be present in two or more areas of cognition. The onset of the deficits has been between the ages of 40     and 90 years and finally there must be an absence of other diseases capable of producing a dementia syndrome.
    Possible Alzheimer's disease: There is a dementia syndrome with an atypical onset, presentation or progression; and without a known     aetiology; but no co-morbid diseases capable of producing dementia are believed to be in the origin of it.
    Unlikely Alzheimer's disease: The patient presents a dementia syndrome with a sudden onset, focal neurologic signs, or seizures or gait     disturbance early in the course of the illness.

For futher subject matter in this section:-

a) Click HERE for Early Detection Biomarkers

b) Click HERE for Brain Pathology

c) Click HERE for Cerebrospinal Fluid (CSF) Measures

d) Click HERE for Neuroimaging

Vertical Brain Section PET Brain Scans Loss of Neurons and Brain Shrinkage Brain PET Scans Alzheimer's Brain Shrinkage Prepartion of Brain Slices Comparison of Metabolic Activity Neurofiibrillary Tangles of Tau Amyloid Plaques; Creation and Appearance with different etchants PET Scans Cortical Atrophy easily generate web photo galleriesby v6.1