Cognitive Component Structure of a Neuropsychological Battery Administered to Cognitively-Normal Adults in the SIU Longitudinal Cognitive Aging Study.

We used principal component analysis (PCA) to examine the component structure of a neuropsychological test battery administered to 943 cognitively-normal adults enrolled in the Southern Illinois University (SIU) Longitudinal Cognitive Aging Study (LCAS). Four components explaining the most variance (63.9%) in the dataset were identified: speed/cognitive flexibility, visuospatial skills, word-list learning/memory, and story memory. Regression analyses confirmed that increased age was associated with decreased component scores after controlling for gender and education. Our identified components differ slightly from previous studies using PCA on similar test batteries. Factors such as the demographic characteristics of the study sample, the inclusion of mixed patient and control samples, the inclusion of different test measures in previous studies, and the fact that many neuropsychological test measures assess multiple cognitive processes simultaneously, may help to explain these inconsistencies.

Many caregivers of persons with memory loss or Alzheimer's disease are unaware of the abilities of their persons with AD to recall their drugs and medical histories.

BACKGROUND: Caregiver awareness of the abilities of those they care for has much practical importance, especially from the safety standpoint. OBJECTIVES: To determine whether the caregivers of persons with memory impairment or Alzheimer's disease know if their persons are able to recall their own drugs and medical histories. METHOD: Persons with prodromal or probable AD (persons with AD) and their caregivers who were visiting our medical school's neurology and internal medicine clinics for routine follow-up care were recruited on the days of their appointments. Sixty-four caregiver-person with AD dyads were recruited. We first asked the caregivers to predict the ability of their persons with AD to answer questions about their drugs and medical histories. We then asked the persons with AD the questions to determine the accuracy of their caregivers' predictions. RESULTS: Considering the caregivers of those with Mini-Mental State Exam scores ≥24, 41% incorrectly predicted whether their persons with AD could recall the number of drugs they were taking, 24% incorrectly predicted whether they could recall the names of the drugs, and 34% incorrectly predicted whether they could recall why they were taking the drugs. Most of the caregivers' errors were overestimations. As expected, the persons with AD themselves had much difficulty in answering the questions; only 30% could recall the number of drugs they were taking, only 14% could recall the names of the drugs, and only 16% could recall why they were taking the drugs. CONCLUSIONS: Many caregivers of persons with memory impairment or AD are unaware of their persons' inability to recall their drugs and medical histories. Particularly concerning is the relatively high frequency of caregiver overestimations of the abilities of their persons with AD, which highlights a safety concern and presents an opportunity for caregiver education.

The inability of older adults to recall their drugs and medical conditions.

BACKGROUND/OBJECTIVES: Previous research has shown that many older adults without known cognitive impairment are unable to recall basic knowledge about their medical history. We sought to determine whether older adult patients in our own clinic population were able to recall their drug regimens and medical conditions from memory. METHODS: Patients aged 65 years or older with no known cognitive impairment, dementia, or memory loss who were presenting for routine outpatient follow-up in our medical school neurology and general medicine clinics were recruited. Each patient was asked to recall the number and names of their presently prescribed drugs and their associated medical conditions. Each patient was also administered a Mini-Mental State Examination (MMSE) cognitive screening test (range 0-30). RESULTS: Most patients were unable to recall their drug regimens or their medical conditions. Of 99 patients taking drugs, only 22% correctly named their drugs from memory, and only 34% correctly named their medical conditions associated with the drugs. Fewer than half (49%) correctly recalled the number of drugs they were taking. Poor recall performance was evident even in high-cognitive (MMSE>27) patients. CONCLUSION: The accuracy of recall memory in older adults regarding their drugs and medical conditions may be poor, which has important implications towards medication reconciliation within meaningful-use doctrine. Clinicians treating older adults should be very cautious before relying on their patients' memories for accurate recall of their medical conditions, their drug regimens, and even the number of drugs they are taking.

Using the telephone to call for help and caregiver awareness in Alzheimer disease.

We assessed the ability of 73 patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) from our outpatient clinic to demonstrate how they would use the telephone to call for help in case of an emergency. We also assessed their caregivers' awareness of their abilities. Overall, 44% of the patients did not demonstrate how to call for help correctly if they had no written telephone number to call, and 18% did not when they had a written number. There was an association between the abilities of the patients and their Mini-Mental State Examination (MMSE) scores, with the patients with the lowest scores having the most difficulty (P < 0.0001). Surprisingly, 21% of those with MMSE scores 26-30 did not use the telephone correctly when they had no written number. Of the caregivers, 31% were incorrect in predicting their patients' abilities for the first task, and 11% were incorrect in predicting the second task. We conclude that AD patients lose their ability to use the telephone to call for help as their illness progresses. Furthermore, many caregivers are unaware of their patients' impairment. These findings highlight safety concerns in AD and suggest that caregivers could benefit from education about potential patient losses.

Knowledge of personal information and caregiver awareness in Alzheimer's disease.

We assessed the ability of 73 patients with Alzheimer's disease (AD) to recall important personal information like their names, their caregivers 'names, their addresses, and their telephone numbers. We also assessed their caregivers' awareness of their abilities. There was an association between the abilities of the patients and their Mini-Mental Status Examination (MMSE) scores, with the patients with the lowest MMSE scores making the most errors. Five to 10 percent of the mildest patients were unable to state their addresses and telephone numbers correctly. The caregivers of the patients with intermediate MMSE scores made the most errors in their predictions, with up to 50 percent being incorrect and up to 37 percent overestimating their patients' abilities. We concluded that AD patients lose their ability to provide personal information as their illness progresses. Caregivers of patients with MMSE ranging from 10 to 25 are the most likely to be unaware of their patients' impairment. These findings highlight safety concerns in AD.

Reversible dementia: a case of cryptococcal meningitis masquerading as Alzheimer's disease.

A 70-year-old man presented to us in 1994 with a three-year history of worsening dementia. With the exceptions of a Mini-Mental State exam score of 20 and an inability to tandem walk, his physical and neurological examinations were normal. His past medical history revealed that in 1992 he had been evaluated at another institution for memory impairment and bifrontal headaches. A spinal tap had been done in 1992 showing elevated protein, reduced glucose, and a pleocytosis; his CSF fungal culture and cryptococcal antigen test were negative. He subsequently was lost to follow-up, and although his headaches had resolved, his mental status had continued to worsen. In 1994 his CSF cryptococcal antigen was positive, and his CSF fungal culture grew C. neoformans. He gradually improved with treatment for cryptococcal meningitis (CM). With the exception of mild memory impairment, in 2003 he and his family thought that his mental status had returned to normal. This case emphasizes that: 1) CM should always be kept in the differential diagnosis of dementia; 2) CM may be extremely insidious and difficult to diagnose; and 3) if one is to rule out unequivocally all possible reversible causes of dementia, one should perform a spinal tap.

The clinical diagnosis of Alzheimer's disease without the use of head imaging studies. A cliniconeuropathological study.

Although head imaging studies are frequently used in the work-up of dementia, published criteria for the clinical diagnosis of Alzheimer's disease (AD) do not require them. Since our brain bank contains cases in which physicians had specifically diagnosed AD without using a head imaging study, we thought it of interest to investigate the accuracy of their clinical diagnoses. We retrospectively reviewed 911 consecutive dementia cases for those clinically diagnosed as either AD or senile dementia (SD). Twenty-one were identified in which head imaging studies had not been used, each diagnosed as AD or SD by a different physician. In only three had the physician reported a reason why a study was not done. In all 21 cases the primary neuropathological cause of the dementia was AD. Neuropathology in addition to AD was also noted, including cortical Lewy bodies in three, infarcts on gross examination in three, multiple microscopic infarcts in four, and multiple cerebral metastases in one. Acknowledging a number of study limitations, it is remarkable that the judgment of the physicians was correct regarding AD in all 21 cases. It is questionable if a head CT or MRI scan at time of diagnosis would have benefited any of the patients.

The Mini-Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Since patients with dementia with Lewy bodies (DLB) tend to have greater impairment of attention and construction and better memory ability on neuropsychological tests than patients with Alzheimer's disease (AD), we determined if the items that measure attention, memory, and construction in the Mini-Mental State Examination (MMSE) help to distinguish DLB from AD early in the course of the dementia. DESIGN: We retrospectively studied the first available MMSE exam for each of our patients with DLB or AD and compared their MMSE subscores for attention, memory, and construction. SETTING: A university dementia brain bank in central Illinois, USA. PATIENTS: All patients with neuropathologically-proven DLB or AD with MMSE scores > or =13. RESULTS: We identified 17 DLB and 27 AD patients for whom we had MMSE exams. The attention and construction subtest scores of the DLB group were worse (p=0.0071 and p=0.0038, respectively) than those of the AD group. The memory subscores of the DLB group were better, although the difference did not reach statistical significance (p=0.22). When a mathematical equation was used to combine the three subscores with equal weighting (Attention-5/3Memory+5.Construction), the scores of the DLB group were worse (p=0.00007). Using this equation, a score less than 5 points was associated with DLB with a sensitivity of 0.82 (95% Confidence Interval (CI)=0.57-0.96) and a specificity of 0.81 (95% CI=0.62-0.94). CONCLUSIONS: Our findings support the work of others regarding the relative neuropsychological impairments of DLB and AD and indicate that the MMSE may be helpful in the differentiation of DLB and AD.

Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway.

Purpose: To assess the potential of delivering nerve growth factor (NGF) to the brain along the olfactory neural pathway for the treatment of Alzheimer's disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to anesthetized rats. The rhNGF concentrations in the brain were determined by enzyme-linked immunosorbent assay (ELISA). Results: Following olfactory administration, rhNGF reached the brain within an hour, achieving a concentration of 3400 pM in the olfactory bulb, 660­2200 pM in other brain regions and, 240 pM and 180 pM in the hippocampus and the amygdala, respectively. In contrast, little or no rhNGF was found in the brain following intravenous administration. Conclusions: A significant amount of rhNGF can be delivered to the brain via the olfactory pathway. The detection of rhNGF by ELISA indicates that rhNGF is delivered to the brain relatively intact. The rapid appearance of rhNGF in the brain suggests that it may be transported by an extraneuronal route into the brain via intercellular clefts in the olfactory epithelium. Further work to clarify the transport mechanism is underway. The olfactory pathway is a promising, non-invasive route for drug delivery to the brain, which has potential for the treatment of neurodegenerative diseases including Alzheimer's disease.