Mohammed T. Abou-Saleh

DISTINGUISHING DEPRESSION FROM DEMENTIA 299This is particularly true in those cases where diagnosticuncertainty is high.LABORATORY EVALUATIONFor many years attempts have been made to find a reliablebiological marker for depression that could be used to develop asensitive and specific laboratory test. Early on, investigatorsexamined the use of the dexamethasone suppression test (DST), aneuroendocrine measure of the functioning of the hypothalamic–pituitary–adrenal axis, to distinguish depression from dementia.Although the test appeared to have some discriminatory ability insome of the very early studies 23,24 , subsequent research failed todemonstrate its usefulness 25–29 . Presently, the DST is not a routinepart of a depression or dementia work-up.Laboratory studies that should be a routine part of theassessment of dementia include a complete blood count (CBC),urinalysis, serum chemistry panel, liver function tests, thyroidfunction, serum vitamin B 12 and folate levels, and syphilisserology 8,30 . A number of these tests are also useful in theevaluation of depression. The most commonly cited are a CBC,serum electrolytes, serum vitamin B 12 level, serum folate level, andthyroid function. While these laboratory studies do not necessarilyhelp to distinguish depression from dementia, they can helpto evaluate a number of possible common etiologies andcontributing factors. Should any of these tests have positiveresults, steps should be taken to correct the abnormality and thepatient should then be reassessed for depression or dementia.Genetic testing is beginning to receive much attention as apossible aid in diagnosing various dementing disorders. EarlyonsetAD comprises both sporadic cases and those that are nowknown to represent a collection of single-gene disorders. Specificmutations in three genes have been associated with the earlyonset,familial-pattern AD. The identified genes are the amyloidprecursor protein (APP) gene on chromosome 21, presenilin-1(PS1) gene on chromosome 14, and presenilin-2 (PS2) gene onchromosome 1 31 . In cases where early-onset dementia is suspected,genetic testing is indicated to help confirm the diagnosis and toprovide additional information to be used in counseling thepatient and family members.In the more common late-onset form of AD, one gene,apolipoprotein E (APOE), located on chromosome 19, has beenassociated as a risk factor. This gene has three common isoforms,2, 3 and 4. Research has shown that the isoform 4 is associatedwith the development of AD in a dose-dependent manner, andthat the isoform 2 may be protective for AD in a dose-dependentmanner 31–35 . Thus, the more copies of the 4 allele one carries inone’s genotype, the higher the risk for developing AD. Onecomplicating factor in using this genetic test in the differentialdiagnosis of dementia and depression is that the 4 allele has alsobeen associated with the development of late-onset majordepression in a study by Krishman et al. 33 While genetic testingfor APOE isoforms can be another helpful piece in distinguishingdementia and depression, it is far from conclusive and is currentlynot a routine part of a work-up for depressed, cognitivelyimpairedpatients.ELECTROENCEPHALOGRAPHY EVALUATIONA great deal of research has been conducted examining the abilityof electroencephalography (EEG) studies to aid in the diagnosesof depression and dementia. In a literature review of EEG of theelderly, Klass and Brenner 36 reported several reasons why an EEGmay be helpful in the evaluation of dementia. First, it mayconfirm that an abnormality of cerebral function exists. Second, itmay indicate that a focal process is present, rather than a diffuseprocess. Third, it may find that a previously unidentified seizuredisorder is present. Finally, certain dementing processes, such asCreutzfeldt–Jakob disease, have pathognomonic EEG change andthus the EEG can be diagnostic in those cases. The authorsconcluded that, in depression, the awake EEG is usually normaland when abnormalities are found they most often are mild.As abnormalities of sleep are part of the core symptoms ofdepression, sleep studies using EEG have been studied extensivelyfor many years in an attempt to find objective variables that couldaid in the diagnosis of depression. Variables that have consistentlybeen found in depression include increased rapid eye movement(REM) activity, increased sleep latency, decreased REM latency,increased REM density and high rates of sleep onset REM ascompared to normal control subjects 37,38 . Dykierek et al. 38 studiedthe REM sleep parameters that could be useful in differentiatingAD from normal aging and depression in the geriatric population.They found that they were able to correctly classify 86% of thepatients studied using REM density and REM latency measures.In their study, depressed patients tended to have increased REMdensity and decreased REM latency, while demented patientstended to have decreased REM density and normal to increasedREM latency. While the use of EEG and sleep studies are not astandard part of a dementia and depression work-up, in selectedcases they may provide additional information that could behelpful to the clinician.NEUROIMAGINGRecent years have seen significant advances in the development oftechnology for imaging the central nervous system. Although thevalue of neuroimaging in the work-up of dementia and geriatricdepression is controversial, many authors present strong argumentsfor its diagnostic utility. The rationale for the use ofmagnetic resonance imaging/computed tomography (MRI/CT)scans in the work-up of dementia includes the following: (a)neuroimaging contributes to increased diagnostic accuracy andmay detect occult lesions not evident on clinical examination; (b)most physicians’ clinical skills in diagnosing AD are not sufficientto abandon imaging; (c) CT or MRI may identify potentiallytreatable causes of dementia missed by clinical evaluation; (d)imaging protects against possible malpractice suits 39 . The argumentsagainst the routine use of neuroimaging include: (a) lack ofcost-effectiveness and low yield (prevalence of 5 5% for clinicallysignificant findings); (b) lack of influence on eventual outcome; (c)imaging may result in unwanted procedures (e.g. surgery) or causedistress to patients; (d) benign small vessel changes on MRI oftenresult in overdiagnosis of vascular dementia (false positives) 40 .Historically, the use of neuroimaging in the work-up ofdepression has not been as strongly recommended as it has inthe work-up of dementia. However, recent research of thepossibility of vascular and degenerative etiologies of geriatricdepression has raised the issue of whether neuroimaging should bepart of the work-up of geriatric depression 41 . As will be discussedlater in this chapter, geriatric depression is becoming increasinglyrecognized as a heterogeneous illness with multiple possibleetiologies, including cerebrovascular disease and neurodegenerativedisease, as well as the genetic and psychosocial etiologiesrecognized in the general adult population. As these possibleetiologies become better established, the use of neuroimaging maybecome more helpful in the classification of geriatric depression,thus impacting treatment and prognosis.Recent research on the diagnosis of AD using MRI estimatedmeasurements of the temporal lobes has demonstrated impressivesensitivity and specificity. O’Brien et al. 42 , in a study to determinethe utility of temporal lobe MRI in distinguishing AD from