supportive of the diagnosis of AD, and may be helpful to differentiate AD, FTD, and CJD.
MR Angiography (MRA)
• MRA allows for examination of cerebral arterial vasculature in patients with suspected cerebrovascular disease, and
• Cerebral vasculitis is a possible cause of dementia.
Brain and Meningeal Biopsy
• Biopsy (Bx) sampling may be helpful in the diagnostic approach to rare cases of dementia for which a reliable diagnosis cannot be established on the basis of clinical symptoms, CSF parameters, EEG, and MRI results, e.g. CJD, CNS vasculitis, and potentially treatable neoplasms or sarcoid.
Genetic Test
• The genetic test for apolipoprotein E4 (apoE4): In general apoE4 is associated with increased risk of developing AD and other neurodegenerative disorders.
Neuropsychologic Evaluation
• To diagnose early dementia and to rule out pseudodementia††. Patients with pseudode-mentia often have a pervious history of depression or a family history of mood disorder.
CLINICAL NOTES
• Before confirming dementia, rule out benign forgetfulness of the elderly, also known as age-associated memory impairment, or MCI, i.e.
dementia not so progressive or serious that it impairs reasonably successful and productive daily functioning
• Dementia is diagnosed from the history and basic examination, especially cognitive testing (e.g. The Mini-Mental Scale Exami-nation,8 i.e. MMSE‡‡; St. Louis University Mental state examination, i.e. SLUMS)9 and confirmed by psychometric testing (e.g. the Wechsler test and/or the Stanford-Binet Intelligence Scales)
• The MMSE is commonly used as a screening tool to detect dementia. However, it performs poorly in identifying persons with mild neurocognitive disorder. The SLUMS examination is a 30-point screening questi-onnaire that tests for orientation, memory, attention, and executive functions, and is possibly better at detecting mild neurocog-nitive disorder, which the MMSE failed to detect10
• MMSE is also been found to be biased by age and education level. Statistical data indicates that its appropriate cut-off scores can improve the sensitivity of culturally modified versions of the MMSE. A 7 minute mental screening (7MS) tool§§, consistingof 4 brief tests (enhanced cued recall, temporal orientation, verbal fluency, and clock drawing) to distinguish between patientswith probable AD and healthy control subjects appears
†† Pseudodementia is a term used to describe the reversible cognitive impairment associated with major depressive disorder in older adults. The use of this term has been disputed by some investigators who note that though severe depression can cause real cognitive impairment, the condition is treatable (unlike irreversible dementias such as AD). When depression is treated, many experience improvement in cognitive function, and some go on to develop dementia within 2 years; therefore, there is nothing pseudo about the disability resulting from severe depression.
(Ref. McAllister TW. Overview: pseudodementia. Am J Psychiatry. 1983 May; 140(5):528-33. [ PMID: 6342420]).
‡‡ MMSE is only a formal screening procedure to quantify cognitive impairment; it is not diagnostic, but can be used over a period of time to follow progression of dysfunction.
Further cognitive assessment is indicated in specific patients to confirm dementia.
§§ Described by Solomon and colleagues, the 7 minutes screening battery takes approximately 7 to 11 minutes.
Diagnosis: A Symptom-based Approach in Internal Medicine 78
highly sensitive to AD, and may be useful in helping to make initial distinctions between patients experiencing cognitive changes related to the normal aging process, and those experiencing cognitive deficits related to dementing disorders such as AD. It has reasonable inter-rater and test-retest reliability, can be administered in a brief period, and requires no clinical judgement and minimal training.11-13
• Unless the patient has obvious and profound cognitive impairment, it is generally advisable to first interview him or her alone, followed by an interview with a close family member or caregiver (Table 12.4).14
Table 12.4: Questions for relatives to detect possible early dementia
• Have you noticed any change in personality?
• Have you noticed increased forgetfulness or anxiety about forgetting things (such as using lists more, etc)?
• Have any activities been given up (hobbies and interests, shopping, dealing with finances) and why?
• Have you noticed nocturnal confusion or muddling when out of usual routine or environment, or unusual avoidance of new circumstances?
• Have you noticed surprising failure to recognize people (such as more distant relatives)?
• Have you noticed undue difficulty in speech?
• Have changes been gradual or has there been sudden worsening?
• In an elderly with suspected dementia, cognitive testing should be ideally performed after assessing their visual and hearing status.
Their visual and hearing deficit may add to confusion and misinterpretation of end result, leading falsely being classified them as demented. Patients with early or doubtful dementia should be screened periodically up to six months and possibly at intervals thereafter
• Ten early warning signs—Due to time constraint, it is difficult to perform screening test on all elderly patients coming to the office. Therefore, particular attention to the presence of warning signs suggestive of cognitive impairment is a useful adjunct to maximize the gain:
1. Memory loss that is getting worse, e.g.
cannot remember recent information, forget names and appointments;
2. Difficulties with familiar activities, e.g.
housewife to prepare a meal;
3. Language problems, e.g. has trouble expressing thoughts, difficulty finding right words;
4. Problems with spatial and temporal orientation, e.g. get lost at familiar place;
5. Impaired capacity of judgement, e.g.
dress inappropriately;
6. Problems with abstract thinking, e.g.
financial mistakes, simple miscalculations;
7. Leaving things behind, losing things;
8. Mood swings and behavioral changes, e.g. sudden mood swing without discernible cause, explosive outbursts;
9. Personality change, e.g. a friendly person becomes unexpectedly angry, jealous; and 10. Loss of initiative, e.g. lose interest in hobbies, excessive procrastination, failure to thrive.
• Some of the potentially reversible causes of dementia should be considered before a diagnosis of AD is made (Table 12.2).
• History should include drug list, head trauma, alcoholism, gastric surgery, risk factors for HIV, functional disabilities, degree of social support, and familial disorders.
• Family history— As many as 40-50% of patients with FTD have an affected family member.
• Drug therapy of dementia—Although some drugs have shown low risk for causing cognition disorders in research studies, risk may be increased in frail older adults taking several medications, and each case should be reviewed carefully.15
• As cognitive decline is a feature of number of medical conditions, the physical and systemic review must be thorough and detailed. Special attention must be paid for signs of common problems at the patient’s age, including:
Nutritional status, anemia
Dementia 79
Audiovisual loss
Hygiene – oral, feet, perineum
Physical abuse or neglect
Issues of poor balance when standing up or walking or gait
Localizing or lateralizing motor signs
Signs of extrapyramidal lesion (parkinso-nism)
Other systemic disorder (metabolic syndrome16,17 hypertension, hypoten-sion,18 hypothyroidism).
• Psychiatric assessment:
Depression in the elderly may mimic dementia, and may even coexist in a significant number of individuals (vide supra: pseudodementia).
Patients with mild HIV dementia commonly present with psychiatric symptoms of depression and anxiety.
Therefore, screening all patients with HIV infection who present with depression for early HIV dementia is imperative.
• Among a long list of the differential diagnosis of dementia, four common diseases — AD, VaD, (Table 12.5), DLB, and FTD — should be considered, based on history, physical examination, and simple neuropsychological evaluation. Although depression, delirium, psychosis, aphasia, and mild cognitive impairment share some features with dementia, each is a distinct syndrome with its own differential diagnosis. It is important to consider all of these syndromes when evaluating a patient with suspected dementia.
AD—Memory decline is the hallmark of cognitive change in AD. In the early stage, memory impairment for recent events is common whereas long-term memory remains intact. As the disease progresses, individuals with AD are increasingly unable to recall more distant memories.
VaD—Typical cases are usually seen with atherosclerotic comorbidities (diabetes
mellitus, hypertension, coronary heart disease, and peripheral artery disease).
The onset of cognitive decline is either subtle or abrupt, and there is psycho-motor slowing, executive dysfunction, focal cognitive deficits and motor signs.
DLB—Clinical features are fluctuating cognitive impairment over weeks or months affecting memory and higher cortical functions (language, visuospatial ability such as clock drawing or copying of a complex figure, or reasoning); mild spontaneous extrapyramidal symptoms; recurrent visual hallucinations, and parkinsonism, with intervening episodic lucid interval. In terms of making a diagnosis, the two most confusing diseases are DLB and Parkinson’s disease with dementia (PDD) because the clinical features are similar.
FTD—Personality and behavioral changes (apathy, withdrawal, mutism) are predominant with less prominent memory loss early in the course;
frequently FTD is misdiagnosed as personality disorders or late-onset psychiatric disorders.
• Aging affects the clinical presentation of both hypothyroidism and hyperthyroidism. Some of the classic clinical features seen in younger
Table 12.5: Alzheimer’s disease and vascular dementia:
the differential diagnosis
Type Alzheimer’s disease Vascular dementia
Onset Gradual May be sudden
Progression Steady decline Stepwise decline Motor system Normal Focal deficits
typical Neuroimaging Normal or May suggest findings atrophy vascular disease
Gait Normal May be abnormal
Comorbid No causative role Hypertension,
illness diabetes, CHF,
atrial fibrillation, IHD as
precipitating causes
Diagnosis: A Symptom-based Approach in Internal Medicine 80
patients (e.g. cold intolerance, weight gain in hypothyroidism; and tremor, nervousness, polyphagia, increased sweating in hyperthy-roidism) are absent in elderly patients. Also, apathetic hyperthyroidism (i.e. paradoxical presentation of hyperthyroidism with fatigue, psychomotor slowing, depression, and weight gain) may also occur in this population.
Moreover, the common clinical features of hypothyroidism (e.g. fatigue, constipation, cognitive loss) are often attributed to normal aging. These factors, along with the fact that hypothyroidism has an insidious onset and affects multiple organ systems, may cause considerable delay and difficulty in diagnosis.
Therefore, it is important to have a high index of suspicion and a low threshold for screening for thyroid dysfunction in elderly patients who present with vague, nonspecific symptoms associated with MCI.
RED FLAGS
• Dementia and delirium can appear in the same patient; however, it is important to distinguish dementia from delirium (acute metabolically induced state of fluctuating consciousness).Table 12.6 compares the features of delirium with those of dementia
• When dementia and delirium coexist, making it difficult to separate them clinically, it is not appropriate to give a patient a new diagnosis of dementia during a state of delirium. With serial observations as the delirium resolves, it becomes possible to differentiate them
• HIV dementia may manifest with acute-onset psychotic symptoms including delusions and hallucinations, and these patients are at a higher risk for suicidal and homicidal ideation. The initial interview should include screening for possible suicidal and homicidal ideation
• “Despite the reemergence of syphilis with the AIDS epidemic, neurosyphilis is often neglected in the differential diagnosis of patients with aseptic meningitis and mental status changes who are negative for the HIV.
The high mortality rate associated with delay in recognition, diagnosis, and treatment of neurosyphilis obligates its inclusion in the differential of young patients with cognitive decline.”19
• The mere presence of cerebral atrophy on a scan should not be taken as evidence of dementing process. Atrophy can occur in individuals with no cognitive impairment.
SELECTIVE GLOSSARY
Normal pressure hydrocephalus—NPH describes hydrocephalus in the absence of papilledema and with normal CSF opening pressure on lumbar puncture. The clinical symptom complex is characterized by abnormal gait, urinary incontinence, and dementia. It is an important clinical diagnosis because it is a potentially reversible cause of dementia. The features of raised intracranial pressure are generally absent. The syndrome mainly occurs in the seventh or eighth decades of life. Possible etiologic factors include head
Table 12.6: Comparison of features of delirium and dementia
Delirium Dementia
Acute onset Insidious onset
Profound confusion, clouding Clear consciousness of or impaired consciousness,
drowsy, anxiety, agitation, bewilderment
Perceptual abnormalities Global impairment of cerebral (illusions, hallucinations, functions (e.g. recent memory, imaginary conversations intellectual impairment, personality, or activities) and behavior abnormalities) Paranoid ideas/delusions; Progressive course fluctuating course with
lucid intervals
Reversible Irreversible
Dementia 81
injury, subarachnoid hemorrhage, meningitis, and CNS tumor. The most reliable marker of NPH is the characteristic magnetic gait in which patient has great difficulty in lifting feet off the ground while upright. This gait disorder looks like a very severe shuffling gait of PD with marked difficulty taking the first step (start hesitation) or turning.
However, rigidity, tremor, and slowing of rapid, alternating movements that are common with PD are less commonly observed in NPH.
Incontinence is usually urinary but may be fecal.
In earlier stages, patients may complain of urgency and frequency rather than true incontinence. Dementia is characterized by prominent memory loss and bradyphrenia, i.e.
slowness of thought processes. MRI assessment of CSF flow is found to be a promising technique for evaluation of patients with suspected NPH.
Mild cognitive impairment20-22— MCI is a syndrome defined as cognitive decline greater than expected for an individual’s age (generally older than 65 years) and education level, but that does not interfere notably with activities of daily life. Several terms have been suggested to identify cognitive disorders without dementia. Benign senescent forgetfulness, age-associated memory impairment and aging-age-associated cognitive decline are considered to fall within the limits of normal aging. A recently proposed term, MCI, as opposed to the terms mentioned above, identifies a transitional state between normal aging and dementia. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years.
Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as alcoholism, smoking, obesity, systolic hypertension, etc. Recently, it has been proposed to classify mild cognitive impairment
according to memory and nonmemory involvement as amnestic, multiple domain and nonmemory single domain clinical subtypes.
However, further studies are suggested to arrive at a consensus on the diagnostic criteria for MCI, determining the subgroups and its treatment modalities.
REFERENCES
1. Web site- http://www.behavenet.com/capsules/
disorders/alzheimersTR.htm. Accessed on 06.10.08.
2. Rockwood K, et al. The diagnosis of “mixed”
dementia in the Consortium for the Investigation of Vascular Impairment of Cognition (CIVIC). Ann N Y Acad Sci 2000;903:522-8. [PMID: 10818547].
3. Kenneth M, et al. Mixed dementia: Emerging concepts and therapeutic implications. JAMA 2004;292(23):2901-08 [PMID: 15598922].
4. Schreiter Gasser U, et al. Alzheimer disease versus mixed dementias: An EEG perspective.
Clin Neurophysiol 2008 Sep 1.[PMID: 18768349].
5. Moor AR, et al. Drug-induced cognitive impairment in the elderly. Drugs Aging 1999;
15(1):15-28. [PMID: 10459729].
6. Gray SL, et al. Drug-induced cognition disorders in the elderly: Incidence, prevention and management. Drug Saf 1999 Aug; 21(2):101-22.
[PMID: 10456379].
7. Felber SR. Magnetic resonance in the differential diagnosis of dementia. J Neural Transm 2002;
109(7-8):1045-51[PMID: 12111442].
8. Available at web site: http://www.hospital m e d i c i n e . o r g / g e r i r e s o u r c e / t o o l b o x / p d f s / folstein_mini-mental.pdf
9. Available at web site: http://medschool.slu.edu/
agingsuccessfully/pdfsurveys slumsexam_05.pdf.
10. Tariq SH, et al. Comparison of the Saint Louis University mental status examination and the mini-mental state examination for detecting dementia and mild neurocognitive disorder—a pilot study.
Am J Geriatr Psychiatry 2006;14(11):900-10.
[PMID: 17068312].
11. Paul R. Solomon, et al. A 7 Minute Neurocognitive Screening Battery Highly Sensitive to Alzheimer’s Disease. Arch Neurol 1998;55(3):349-55.
12. de Jager CA, et al. Utility of the Malayalam translation of the 7- minute screen for Alzheimer’s disease risk in an Indian community. Neurol India [serial online] 2008 [cited 2008 Oct 11]; 56:161-6. Available from:
http://www.neurologyindia.com/text.asp?2008/
56/2/161/41994
Diagnosis: A Symptom-based Approach in Internal Medicine 82
13. Mathew R, et al. Issues in evaluation of cognition in the elderly in developing countries. Ann Indian Acad Neurol [serial online] 2008 [cited 2008 Oct 11];11:82-88.
Available from: http://www.annalsofian.org/
text.asp?2008/11/2/82/41874
14. Macdonald AJD. ABC of mental health: Mental health in old age. BMJ 1997;315:413-7.
15. Lenzer J. FDA warns about using antipsychotic drugs for dementia. BMJ 2005;330:922, doi:
10.1136/bmj.330.7497.922-c
16. Ho RC, et al. Metabolic syndrome and cognitive decline in Chinese older adults: Results from the Singapore longitudinal ageing studies. Am J Geriatr Psychiatry. 2008;16(6):519-22. [PMID:
18515697].
17. Yaffe K, et al. Metabolic syndrome and cognitive decline in elderly Latinos: Findings from the
Sacramento Area Latino Study of Aging study. J Am Geriatr Soc 2007;55(5):758-62. [PMID:
1749319].
18. Moretti R, et al. Risk factors for vascular dementia:
Hypotension as a key point. Vasc Health Risk Manag 2008;4(2):395-402. [PMID: 18561514].
19. Schiff E, et al. Neurosyphilis. South Med J 2002 Sep;95(9):1083-7. [PMID: 12356119].
2 0 . Gauthier S, et al. Mild cognitive impairment. Lancet 2006 Apr 15;367(9518):1262-70. [PMID:
16631882].
21. Gimzal A, et al. Mild cognitive impairment. Turk Psikiyatri Derg 2004 Winter;15(4):309-16. [PMID:
15622511].
22. Portet F, et al. What is a mild cognitive impairment? Rev Prat 2005;55(17):1891-4. [PMID:
16396229].
SYNOPSIS
The definition of diarrhea is somewhat contro-versial. It depends on the patient’s as well as the physician’s perspective. Scientifically, diarrhea exists if more than 200 g stool is passed daily, which is best determined by a 72-hour stool collection.1
Patients usually consider diarrhea as being an increase in the daily frequency, liquidity, or volume of the stool. Clinically, it may be defined as more than 3 bowel movements in a day.
However, there may be some exceptions to this definition. Stool weight depends on dietary intake (e.g. Indian diet has high fiber content, and hence they have increased stool weight >200 g/day);
therefore, stool weight by itself is an imperfect criterion to define diarrhea. Moreover, patient’s understanding of ‘diarrhea’ varies considerably—
many complain of diarrhea when their stool is loose in consistency, while others complain only when their stool frequency increases.2 Therefore, a more practical definition of diarrhea may be taken as, ‘ too frequent passage of too fluid stools’, as compared to patient’s baseline pattern.
Diarrhea that lasts less than 14 days is referred to as acute, while chronic diarrhea is
defined as diarrhea that lasts for more than 4 weeks, and that often persists unless therapy is instituted (unlike acute diarrhea, which is usually self-limited). Diarrhea that lasts 14 days and resolves within a month is generally referred to as persistent acute diarrhea. Diarrhea is also classified into groupings such as osmotic versus secretory, infectious versus noninfec-tious, and inflammatory versus noninflamma-tory. Although each of these etiological factors is helpful for understanding the pathophysio-logy of individual diarrheal disease, most diarrheas are complex, and are produced by a combination of mechanisms.
Acute diarrhea is usually associated with abdominal colicky pain, urgency, tenesmus, nausea and vomiting, watery stools, with or without blood or mucus. Systemic symptoms such as fever and myalgia may be present. In severe cases of diarrhea, urgency of defecation and fecal incontinence is a common event.
In chronic diarrhea, the history is often nonspecific and physical findings are lacking.
Many patients do not seek medical attention unless their diarrhea is associated with other symptoms, such as weight loss, fecal inconti-nence, rectal bleeding, or abdominal pain.
Diarrhea
13
CHAPTER
84
The majority of cases of acute diarrhea are benign and self-limiting; but in selected clinical settings such as elderly, dehydrated, immuno-compromised, or patients on immunosuppressive therapy, this aliment can be life-threatening.
Further, the diagnosis of functional disease in patients with chronic watery diarrhea should be performed with caution, since in most cases there is an organic cause that justifies diarrhea.3,4
The goal of the initial evaluation of an adult with diarrhea, therefore, is to differentiate benign patients from more serious or chronic disorders needing thorough investigations because of the possibility of more serious underlying disease.
Although the evaluation can be taxing, making an accurate diagnosis is rewarding, because
Although the evaluation can be taxing, making an accurate diagnosis is rewarding, because