The Dementias: Alzheimer's Disease, Vascular, Lewy-Body, Frontotemporal Dementia, and more

This section contains numerous research studies on dementia.  The most common type of dementia around the world is Alzheimer's Disease.  However, there are a large number of other types of dementia.  The next most common types are Vascular or Multi-infarct Dementia, Lewy-Body Dementia, and the Frontotemporal Dementias.  Others include dementias due to HIV, head trauma, Parkinson's Disease, Huntington's Disease, Pick's Disease, Down's Syndrome, Creutzfeldt-Jakob Disease (similar to Mad Cow Disease), and several more.  Better genetic, lab, and scanning tools are allowing more different types of rare dementias to be defined.  These changes are occurring so rapidly that articles summarized from 2003 below are sometimes already out of date.

Dementia consists of memory difficulties and at least one other cognitive problem.  Individuals with memory problems may lose valuables, forget food cooking on the stove, and become lost easily.  Other cognitive problems may cause the individual to have 1) difficulty naming people and common things (aphasia), 2) difficulty with carrying out common tasks when asked, like brushing teeth, combing hair, drawing, dressing (apraxia), 3) recognizing familiar people and objects (agnosia) or 4) increasing problems with abstract thinking, e.g. plan, carry out, and stop doing tasks (executive function).  This latter may show up as difficulty coping with a novel task or planning a budget.  Executive function is tested by asking the individual to name similarities and differences between words, count to 10, say the alphabet, name as many animals as possible in a minute, or to start at 100 and keep subtracting 7.

Depending on the study, 4-10% of the population over 65 have dementia with the prevalence increasing to 20-30% of those over 85.   While diagnosing the presence of dementia is not difficult, determining the precise cause is more difficult and doesn't always make a lot of difference on current treatment strategies.  With improved forms of testing and treatment, this will undoubtedly change.  

Alzheimer's Disease (AD) may comprise up to 70% of all dementia.  It is the 4^th cause of death in U.S.  Diffuse Lewy Body Disease makes up 20% dementia, and vascular dementia 5-10%.  Life expectancy is 3-20 years, averaging 6-9 years, after diagnosis of dementia. In 10%, there is a family history. There is a mutation of an amyloid precursor in some, and mutation two other genes in some. 15% of Parkinson's Disease patients have dementia.  Pseudodementia are conditions that look like dementia but are not.  There may be apathy, anergia, slow responses, decreased attention and memory with depression and sometimes agitation and psychosis.  Thyroid disease may also mimic dementia as well as several less common conditions.

Of course, mild memory difficulties are a very common part of aging affecting the large majority of individuals over age 65. Measurable mental deterioration, just like physical deterioration, starts much earlier in the 30s and 40s in the average person.   Dementia is a more extreme manifestation of this same trend.  Indeed, there is evidence that that some individuals with Alzheimer's in old age already showed subtle signs of mental difficulties in their 20s.

Psychiatric and medical testing can help diagnosis dementia, but actually relatives and friends are better at detecting it, although there is a tendency for some people to overlook the signs.  At the same time, the individuals themselves will often not notice how severely affected they are, while other people who don't have dementia at all will jump to the conclusion that the forgetfulness of everyday life is evidence that they are losing their memory.

Fortunately, there is much that one can do to lower the risk of dementia. 

MMSE: Mild-Moderate-Severe: Mild dementia falls into the Mini Mental Status Exam (MMSE) 20-24 range, moderate 10-19 range, and severe below 10.  Moderate demented patients typically need help with activities of daily living, while severely demented are totally dependent.  For MMSE, see Measurement.

Cognitive Decline Steep 43 Months Before Death: Prospective study of 953 nuns and priests tested yearly with 122 deaths after 6 years. Those dying had lower cognitive baselines but annual loss accelerated 6-fold an average of 43 months before death, although the time period was quite variable. Cognitive decline was evident in nearly all of those who died, but at highly variable rates. Remarkably little cognitive decline was evident in survivors. Decline in episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability also greatly increased about 3 to 6 years prior to death. Rush. Terminal decline in cognitive function. Wilson RS, Beckett LA, et al. Neurology. 2003 Jun 10;60(11):1782-1787

27% with Mild Cognitive Impairment Didn't Progress: A 12 year follow-up study of 90 patients with MCI found that 24 of them did not go on to dementia and Alzheimer's Disease during the next 12 years. Howard Chertkow, McGill Univ. ANA 128th Annual Meeting: Poster 197. Presented Oct. 21, 2003

Reevaluations Document a High Rate of Deterioration from Normal to Demented: Of 499 patients found to be cognitively normal at the Alzheimer's Disease Research Centers, patients reported high rates of depression (39%) and family history of dementia (51%). In follow-up of 36%, of those, 65% received a diagnosis of dementia or mild cognitive impairment. Patients evaluated at memory clinics who are considered cognitively normal may merit periodic re-evaluation. Clinical profile and course of cognitively normal patients evaluated in memory disorders clinics. Edwards ER, Lindquist K, Yaffe K. University of California, San Francisco, USA. Neurology. 2004 May 11;62(9):1639-42. Ed: This study emphasizes the importance of prevention measures being heavily stressed.

Screening Memory Question, MMSE, Neuropsychiatric Testing Misses Most: A 3 year follow-up study found that none of these 3 common techniques were specific enough and all three detected only 18% of future dementias. The screening memory question was the most sensitive but 50% of future dementia had no memory complaints at screening. Getting the reports of collateral sources did better. Detection of Alzheimer's disease and dementia in the pre-clinical phase: population based cohort study. Katie Palmer, Lars Bäckman, et al, BMJ 2003;326:245.

Screening Test: The recall of a five-item name and address, "John Brown 42 Market Street Chicago" and the one-minute verbal fluency for animals combined has a sensitivity and specificity, surpassing the MMSE, to detect dementia in individuals with memory complaints. Brief Screening Tests for the Diagnosis of Dementia: Comparison With the Mini-Mental State Exam. Kilada S, Gamaldo A, et al. Johns Hopkins, National Institute on Aging, National Institutes of Health, Washington University. Alzheimer Dis Assoc Disord. 2005;19(1):8-16

Nursing Home Demented Patients Rarely Seen by Psychiatrists: In a study of 79,000 patients suffering from Parkinson's disease, researchers noted that dementia and depression were very common problems. Despite this, fewer than 10% had been seen by any mental health professional. Analyses of nursing home residents with Parkinson's disease using the minimum data set. Buchanan RJ, Wang S, Huang C, Simpson P, Manyam BV. The Texas A&M University. Parkinsonism Relat Disord. 2002 Jun;8(5):369-80. Ed: In my experience, nursing homes primarily want psychiatrists to fill in on emergencies, rarely seek out psychiatrists, and infrequently try to modify their programs to be receptive to psychiatrists. Psychiatrists, for their part, rarely wish to visit nursing homes because of the very low reimbursement from Medicare and Medicaid for psychiatrist services.  Although very little funds are expended by the federal government for psychiatric services in nursing homes, patients are often receiving sizeable numbers of extremely expensive medications for psychiatric and dementia problems with costs often running one to five thousand dollars a much. Drug companies make huge profits, but patients are often short-changed.

Nursing Home Depressed Get No Psychiatric Consult: In a study of 59 randomly selected Maryland nursing homes, researchers found that psychiatrists were consulted on patients who caused the nursing home problems, i.e., agitation, physical/verbal abuse, wandering, and manic/destructive acts. Depression in retarded and psychotic residents did not trigger a psychiatric consult, even though depression is the most common problems for elderly nursing home patients. Some predictors of psychiatric consultation in nursing home residents. Fenton J, Raskin A, et al.  Veterans Affairs Maryland Health Care Center. Am J Geriatr Psychiatry. 2004 May-Jun;12(3):297-304

STMS May Be Better than MMSE at Detecting MCI: Short Test of Mental Status (STMS) is better than the Mini-Mental State Examination (MMSE) at detecting those likely to develop mild cognitive impairment (MCI) or Alzheimer disease (AD) in a large prospective study of 788 elderly. Mayo Clinic, Archives of Neurology 12/03 2003;60:1777-1781. Ed: This is an old test (Mayo Clin Proc. 1987 Apr;62(4):281-8).  Unfortunately, I have been unable to obtain a copy.

CT Scan Helpful Only in 10% of Cases: Two physicians reviewed standardized data extracted from 146 clinical records, first blind to CT results, and then with CT results. Clinical decisions made with and without the input of CT were compared. CT impacted on diagnosis in an average of 12%, and on treatment plan in 11% of cases. Physicians predicted a priori which cases CT may influence with an average sensitivity of 28%, and specificity of 78.5%. There was no statistically significant relationship between diagnostically uncertain cases and helpful CT scans. Blind to CT physicians appropriately identified cerebrovascular disease with an average sensitivity of 63%, and specificity of 93.5%. Clinical utility of computed tomography in the assessment of dementia: a memory clinic study. Condefer KA, Haworth J, Wilcock GK. Albert Einstein College of Medicine. Int J Geriatr Psychiatry. 2004 May;19(5):414-21. 

Nursing Home Demented Attacked More Often: In a Harvard study by Tomoko Shinoda-Tagawa, 294 nursing home residents who had been injured by another resident were compared with 2000 uninjured. Many violent incidents were unprovoked, but some injured residents seemed to have incited aggressive behavior. Walking into the wrong bedroom or eating from another resident's plate sometimes precipitated an assault.  Injured residents were more likely to be male, to be verbally or physically abusive and to behave inappropriately or disruptively. They were also more likely to wander within the nursing home and to resist care. Residents with borderline-to-mild impairment were five times more likely to be injured, moderately impaired 8-fold, and severely impaired 12-fold. However, they were also more likely to be physically independent. JAMA 2/4/2004;291:591-598.

Money Wasted on Dementia Work-ups: In a study of 269 patients with dementia with an average age of 74, physicians did a full expensive work-up of every patient to attempt to find preventable causes of dementia. These included blood count, biochemical study, vitamin B12 and folic levels, thyroid hormones, and syphilis testing, and CT or MRI scans. In all, 31 patients presented potentially reversible conditions (11.5%), but if depression is excluded, the dementia was only reversible in one patient (0.4%). Researchers concluded that the percentage of patients with reversible causes of dementia in the field of extra-hospital neurology is very low and that the diagnostic studies must be individualized according to the clinical suspicion. Cost effectiveness of the diagnostic study of dementia in an extra-hospital Neurology service. Sempere AP, Callejo-Dominguez JM, et al. Alicante, Spain. Rev Neurol. 2004 Nov 1-15;39(9):807-10

Gait Slowing Increases Risk of Cognitive Impairment Progressing: The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling elderly of age 74. Those with cognitive impairment in combination with gait and motor slowing were the most likely to develop dementia over the next 6 years (OR 5.6) and to die (OR 3.3). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study. Waite LM, Grayson DA, et al. University of Sydney. J Neurol Sci. 2005 Mar 15;229-230(1):89-93.

Mortality: Vascular Dementia Dies More Quickly: A study of mortality of 3602 adults of the Cardiovascular Health (CHS) Cognition Study over 6.5 years found that those who developed Vascular Dementia were 340% more likely to die (HR: 4.4) vs. 110% more likely for Alzheimer's and 150% for the combined VaD-AD. Adjusted accelerated life models estimated median survival from dementia onset to death as 3.9 years for VaD, 7.1 years for AD, 5.4 years for mixed dementia, and 11.0 years for matched controls with normal cognition. While persons with VaD died primarily from cerebrovascular disease, those with AD/mixed dementia died more frequently from dementia/failure to thrive. Survival following dementia onset: Alzheimer's disease and vascular dementia. Fitzpatrick AL, Kuller LH, et al. University of Washington, Seattle. J Neurol Sci. 2005 Mar 15;229-230(1):43-9.

Depression More Than Triples Rate of Disability in Dementia: In a community-based group of 216 elderly people with low-to-moderate education level, very early dementia alone was strongly associated with functional disability, and this association tripled in subjects with both very early dementia and symptoms of depression, i.e., for very early dementia an 11-fold higher risk for disability, for very early dementia and depression a 37-fold higher risk for functional dependence. Diana De Ronchi, et al. Univ. of Bologna, Italy. . Am J Geriatr Psychiatry. 2005 Aug;13(8):672-85

White Matter Lesions Increased with Depression and Subjective Memory Complaints: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly. In a cross-sectional study of 60 elderly without dementia, but given an MRI, the best correlate of SMC was the severity of depressive symptoms, although SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients. Minetts TS, et al. Sao Paulo Federal University, Brazil. . Am J Geriatr Psychiatry. 2005 Aug;13(8):665-71.

C-Reactive Protein Linked to White Matter Lesions and Lacunar Infarcts: In a 3-year follow-up study of 1033 adults ages 60-90 and free of dementia in the population-based Rotterdam Scan Study, using multivariate regression, higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 and 2.5 for periventricular and subcortical white matter lesion progression). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts. C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. van Dijk EJ, et al. Erasmus Medical Center,  Rotterdam, The Netherlands. Circulation. 2005 Aug 9;112(6):900-5.