Association Between Low-Density Lipoprotein Cholesterol Levels,Statin Use,and Dementia in Patients followed in German General Practices

Abstract

Background:

No studies have been conducted to date on the association between low-density lipoprotein cholesterol (LDL-C), statin use classified into low, medium, and high statin dosages, and dementia in German general practices.

Objective:

The goal of this retrospective case-control study was to investigate the relationship between elevated LDL-C, statins, and dementia in elderly persons followed in general practices in Germany.

Methods:

This study included patients aged 65 or older with an initial dementia diagnosis between January 2015 and December 2019 and at least one documented LDL-C value within the year prior to the dementia diagnosis. These patients were treated in one of 963 general practices which document LDL-C in Germany. Dementia cases were matched to non-dementia controls using propensity scores based on age, sex, and comorbidities. Logistic regression models were conducted to assess a possible association between accelerated LDL-C, statins, and dementia.

Results:

The study included 12,236 patients with dementia and 12,236 non-dementia controls. In total, 2,528 of the dementia patients were diagnosed with vascular dementia. The use of all dosages of statin use was negatively associated with all-cause dementia (OR: 0.80 for low dose, OR: 0.92 for medium dose, and OR: 0.85 for high dose) and with vascular dementia (OR: 0.61 for low dose, OR: 0.77 for medium dose, and OR: 0.74 for high dose). There was no clinically relevant association between elevated LDL-C and dementia.

Conclusion:

A negative association was found between all dosage use of statin therapy and all-cause dementia and vascular dementia in elderly patients in general practices in Germany.

Keywords

Dementia low-density lipoprotein cholesterol statin vascular dementia

INTRODUCTION

Dementia is a severe medical syndrome which is characterized mainly by a significant decline in memory and cognition and a resulting inability to live independently [1]. The prevalence of dementia is increasing dramatically: while there are estimated to have been over 50 million patients affected worldwide in 2019, this figure could increase to 152 million by 2050, a trend supported by an aging population. The related healthcare expenditure is immense, currently reaching an estimated US $1 trillion [2]. In Germany, the current number of people suffering from dementia is estimated at 1.6 million [3, 4]. To date, the only treatment options are symptomatic in nature and include donepezil, rivastigmine, and galantamine [5]. It is therefore very important to analyze possible risk factors of dementia for a better understanding and an improvement of dementia prevention.

Dementia is associated with cardiovascular disease risk factors and atherosclerotic vascular disease [6]. In recent years, many studies have investigated the role of blood lipids and particularly low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of dementia and the different subtypes of dementia, such as Alzheimer’s disease (AD), vascular dementia (VaD), etc. Nevertheless, the evidence remains controversial, with some of these studies reporting a significant association between elevated LDL-C [7 –9] and dementia and others unable to replicate these findings [10 –13].

Guidelines recommend statins (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) as first-line therapy in the management of blood cholesterol [14] and they are the most frequently prescribed lipid-lowering therapy [15]. Recent studies suggest that statins may also have a preventive effect on dementia [16 –18]. However, this remains controversial since other studies did not find any significant association between statins and dementia [19 –21]. In a recent German review [22], the significance of statins in drug-based dementia prevention was assessed rather negatively (see also the Cochrane Review by McGuiness [23]). In any case, a clinical update in 2018 showed that statins have no adverse effect on cognitive functions [24].

To the best of our knowledge, no studies have been conducted to date on the association between LDL-C, statin use classified into low, medium, and high statin dosages, and dementia in German general practices.

The aim of this retrospective study was to analyze the association between pre-diagnostic statin usage, accelerated LDL-C, and the onset of all-cause dementia and VaD in elderly patients treated in general practices in Germany.

METHODS

Database

This retrospective case-control study relies on longitudinal data from the IQVIA Disease Analyzer database. This database contains demographic, clinical, and pharmaceutical variables. This information is obtained by IQVIA in anonymous format from a national sample of general and specialist practices in Germany [25]. Coverage is about 3–5% of all outpatient practices in Germany, depending on the specialty. Diagnoses (International Classification of Diseases, 10th revision [ICD-10]), prescriptions (Anatomical Therapeutic Chemical [ATC] Classification system), and the quality of reported data are monitored by IQVIA based on various criteria (e.g., completeness of documentation, linkage between diagnoses and prescriptions). A study by Rathmann et al. [25] showed that the database is representative of general and specialized practices in Germany. This database has also been used in previous studies focusing on dementia [26 –28].

Study population

This study included patients with an initial diagnosis of all-cause dementia (ICD-10: F01, F03, G30) in 963 general practices in Germany between January 2015 and December 2019 (index date; Fig. 1). Other inclusion criteria applied were as follows: age≥65 years at the index date, an observation time of at least 12 months prior to the index date, and at least one recorded LDL-C value in the 12 months prior to the index date. The average number of documented LDL-C values prior to the index date was 9.7 in dementia and 9.1 in non-dementia patients. The average pre-observation time was 5.6 years in dementia and 5.8 in non-dementia patients.

Fig. 1

Patient flow chart.

Dementia cases were individually matched (1 : 1) to non-dementia controls by age group, gender, index year, and comorbidities known to be associated with dementia (diabetes, ischemic heart diseases, stroke including transient ischemic attack, intracranial injury, epilepsy, Parkinson’s disease, and depression). Controls were included after checking for similar criteria, and a randomly selected visit date between January 2015 and December 2019 (Fig. 1) was used as the index date for this group.

Study outcomes and variables

The main purposes of the study were to examine the distribution of LDL-C in the study population and to assess the association between high LDL-C and the incidence of dementia. The mean LDL-C of each patient was calculated for the whole time period before the dementia index date. Patients were then separated into four groups based on their mean LDL-C (Group 1: mean LDL-C < 100 mg/dl, Group 2 : 100 mg/dl≤mean LDL-C < 130 mg/dl, Group 3 : 130 mg/dl≤mean LDL-C < 160 mg/dl, Group 4:≥160 mg/dl) and the probability of developing dementia was modeled as a function of the LDL-C. The model was also extended to adjust for the use of statin medication by the patients taken in the whole time period prior to the index date. The use of statins was modeled with the aid of a categorical variable with the values 1 (no statin usage), 2 (low statin dosage), 3 (medium statin dosage), and 4 (high statin dosage), where the dosage was defined as shown in Table 1 [29]. To enable the comparison with a reference group (no statin usage), we considered the last statin therapy which patients received.

Table 1

Classification of statin usage

Substance	Low-intensity	Medium-intensity	High-intensity
	(LDL-C reduction < 30%)	(LDL-C reduction 30% to < 50%)	(LDL-C reduction > 50%)
Atorvastatin	-	10–20 mg	40–80 mg
Fluvastatin	20–40 mg	40 mg 2x a day,	-
		or 80 mg
Lovastatin	20 mg	40 mg	-
Pitavastatin	1 mg	2–4 mg	-
Pravastatin	10–20 mg	40–80 mg	-
Rosuvastatin	-	5–10 mg	20–40 mg
Simvastatin	10 mg	20–40 mg	-

Statistical analyses

Possible differences in the sample characteristics between those with and those without dementia were investigated using chi-squared tests for categorical variables and Wilcoxon tests for continuous variables. Two logistic regression models were applied to study the association between LDL-C and dementia incidence. The first model examined the association between the different LDL-C groups and all-cause dementia. The model was also adjusted for the use of statin medication. The second model, likewise, adjusted for the use of statin medication, analyzed the association between the various LDL-C groups and VaD (only ICD-10: F01). LDL-C group 1 (mean LDL-C<100 mg/dl) and the statin group 1 (no statin usage) were the reference groups. p-values<0.05 were considered statistically significant. The analyses were carried out using SAS version 9.4.

RESULTS

The present study included 12,236 patients with and 12,236 patients without all-cause dementia. A total of 2,528 of the dementia cases had VaD. The average age of all-cause dementia patients and their controls was 80.2 (SD 6.4) and that of the VaD cases and controls was 79.5 (SD 6.4). In total, 57.7% of the all-cause dementia cases and controls were female, while the proportion in the VaD study groups was 58.2%. Over one-third of the all-cause and the VaD patients were concomitantly diagnosed with diabetes (34.8% in the all-cause dementia group and 35.35 in the VaD cohort). The proportion of ischemic heart disease and stroke was a bit higher in the VaD patients than in those with all-cause dementia. As desired, the matching procedure resulted in comparable demographic features with no statistically significant differences in the dementia and non-dementia groups. The basic characteristics of study patients with all-cause dementia are displayed in Table 2 and those for VaD in Table 4.

Table 2

Basic characteristics of study patients with all-cause dementia (after 1 : 1 matching by age group, sex, index year, and comorbidities)

Variable	Proportion affected among patients with dementia (%)	Proportion affected among patients without dementia (%)	p
N	12,236	12,236
Age (Mean, SD)	80.2 (6.4)	80.1 (6.4)
Age 65–67	2.8	2.8	1.000
Age 68–70	5.0	5.0
Age 71–73	7.6	7.6
Age 74–76	12.8	12.8
Age 77–79	18.0	18.0
Age 80–82	17.3	17.3
Female	57.7	57.7	1.000
Male	42.3	42.3	1.000
Diagnoses documented within 12 months
prior to the index date
Diabetes mellitus (E10, E11, 14)	34.8	34.8	1.000
Ischemic Heart Disease (I20–I25)	24.3	24.3	1.000
Stroke incl. TIA* (I60–I64, G45)	16.9	16.9	1.000
Intracranial injury (S06)	0.3	0.3	1.000
Epilepsy (G40, G41)	1.2	1.2	1.000
Parkinson’s Disease (G20, G21)	2.7	2.7	1.000
Depression (F32, F33)	18.8	18.8	1.000

*TIA, transient ischemic attack.

Table 3B shows the proportions of patients with and without all-cause dementia in the various LDL-C and statin usage groups in the 12 months prior to the index date. Overall, 22.6% of dementia and 22.1% of non-dementia patients had an average LDL-C value of less than 100 mg/dl before the index date, whereas 15.6% of the dementia patients and 15.4% of the healthy controls fell into Group 4, with an average LDL-C of over 160 mg/dl. The proportions were comparable to those in the section of the study population with VaD (see Table 5B), although it is notable that in the VaD patients, the proportion in the LDL-C group < 100 mg/dl was about 1.5% higher than in the all-cause dementia patients.

Table 3A

Association between the LDL value and all-cause dementia in general practices in Germany

LDL and statin group	Proportion affected among patients with dementia (%)	Proportion affected among patients without dementia (%)	Odds ratio (95% CI)	p
LDL group 1 (<100 mg/dl)	22.6	22.1	Reference
LDL group 2 (≥100 mg/dl,<130 mg/dl)	33.0	34.6	0.94 (0.87–1.00)	0.055
LDL group 3 (≥130 mg/dl,<160 mg/dl)	28.8	27.9	1.01 (0.94–1.08)	0.75
LDL group 4 (≥160 mg/dl)	15.6	15.4	1.00 (0.92–1.08)	0.95

Table 3B

Association between the LDL value, the use of statins, and all-cause dementia in general practices in Germany

LDL and statin group	Proportion affected among patients with dementia (%)	Proportion affected among patients without dementia (%)	Odds ratio (95% CI)	p
LDL group 1 (<100 mg/dl)	22.6	22.1	Reference
LDL group 2 (≥100 mg/dl,<130 mg/dl)	33.0	34.6	0.92 (0.86–0.99)	0.020
LDL group 3 (≥130 mg/dl,<160 mg/dl)	28.8	27.9	0.98 (0.92–1.06)	0.671
LDL group 4 (≥160 mg/dl)	15.6	15.4	0.97 (0.89–1.06)	0.480
Statin group 1 (no statins)	43.0	40.5	Reference
Statin group 2 (low dosage)	5.2	6.1	0.80 (0.72–0.90)	0.0001
Statin group 3 (medium dosage)	45.1	46.0	0.92 (0.87–0.97)	0.004
Statin group 4 (high dosage)	6.7	7.4	0.85 (0.77–0.94)	0.002

Table 4

Basic characteristics of study patients with vascular dementia (after 1 : 1 matching by age group, sex, index year, and comorbidities)

Variable	Proportion affected among patients with dementia (%)	Proportion affected among patients without dementia (%)	p
N	2528	2528
Age (Mean, SD)	79.5 (6.4)	79.5 (6.4)	1.000
Age 65-67	3.8	3.8	1.000
Age 68–70	5.1	5.1
Age 71–73	9.3	9.3
Age 74–76	14.0	14.0
Age 77–79	17.1	17.1
Age 80–82	16.4	16.4
Age 83–85	15.6	15.6
Age 86–88	10.7	10.7
Age 89–91	5.8	5.8
Age 92–94	2.1	2.1
Age≥95	0.2	0.2
Female	58.2	58.2	1.000
Male	41.8	41.8	1.000
Diagnoses documented within 12 months
prior to the index date
Diabetes mellitus (E10, E11, 14)	35.3	35.3	1.000
Ischemic Heart Disease (I20–I25)	26.1	26.1	1.000
Stroke incl. TIA* (I60–I64, G45)	20.9	20.9	1.000
Intracranial injury (S06)	0.4	0.4	1.000
Epilepsy (G40, G41)	1.4	1.4	1.000
Parkinson’s Disease (G20, G21)	2.8	2.8	1.000
Depression (F32, F33)	18.4	18.4	1.000

*TIA, transient ischemic attack.

Regarding the statin usage of the study population, the figures show that over 40% (43.0% of the all-cause dementia cases, 40.5% of the related controls) did not use statins at all, whereas over 40% (45.1% of cases and 46.0% of controls) were medicated with medium-dosage statins. In the VaD group, the proportion of non-statin usage was slightly lower (41.9% of cases, 35.7% of controls). Meanwhile, the proportion of medium-dosage statin users increased (45.4% of cases and 48.9% of controls).

Without adjusting for the use of statins, no LDL-C group showed a significant association with the incidence of dementia for either all-cause dementia or VaD (Tables 3A and 5A).

Table 5A

Association between the LDL-C level and vascular dementia (VaD) in patients treated in general practices in Germany

LDL and statin group	Proportion affected among patients with VaD (%)	Proportion affected among patients without VaD (%)	Odds ratio (95% CI)	p
LDL group 1 (<100 mg/dl)	24.8	22.4	Reference
LDL group 2 (≥100 mg/dl,<130 mg/dl)	32.0	33.7	0.86 (0.74–1.00)	0.045
LDL group 3 (≥130 mg/dl,<160 mg/dl)	28.1	28.8	0.88 (0.76–1.03)	0.105
LDL group 4 (≥160 mg/dl)	15.1	15.0	0.91 (0.76–1.09)	0.305

Table 5B

Association between the LDL cholesterol level, the use of statins, and vascular dementia (VaD) in patients treated in general practices in Germany

LDL and statin group	Proportion affected among patients with VaD (%)	Proportion affected among patients without VaD (%)	Odds ratio (95% CI)	p
LDL group 1 (<100 mg/dl)	24.8	22.4	Reference
LDL group 2 (≥100 mg/dl,<130 mg/dl)	32.0	33.7	0.82 (0.71–0.96)	0.011
LDL group 3 (≥130 mg/dl,<160 mg/dl)	28.1	28.8	0.82 (0.70–0.96)	0.012
LDL group 4 (≥60 mg/dl)	15.1	15.0	0.84 (0.70–1.02)	0.078
Statin group 1 (no statins)	41.9	35.7	Reference
Statin group 2 (low dosage)	5.0	7.0	0.61 (0.47–0.77)	<0.0001
Statin group 3 (medium dosage)	45.4	48.9	0.77 (0.68–0.87)	<0.0001
Statin group 4 (high dosage)	7.6	8.4	0.74 (0.59–0–92)	0.006

After adjusting for the use of statins, there was a very slight association between all-cause dementia and documented LDL-C levels in the second group (OR for Group 2 : 0.92 (95% CI: 0.86–0.99), OR for Group 3 : 0.98 (95% CI: 0.92–1.06), OR for Group 4 : 0.97 (95% CI: 0.89–1.06) as compared to the group 1). Regarding the statin medication, this analysis shows a negative association between the use of all dosages of statins and all-cause dementia (OR 0.80 (95% CI: 0.72–0.90) for low dosage, OR 0.92 (95% CI: 0.87–0.97) for medium dosage and OR 0.85 (95% CI: 0.77–0.94) for high dosage statin) (Table 3B).

The analysis shows a very slight association between VaD and LDL cholesterol in the second and third group but not for the last group (OR for Group 2 : 0.82 (95% CI: 0.71–0.96), OR for Group 3 : 0.82 (95% CI: 0.70–0.96), OR for Group 4 : 0.84 (95% CI: 0.70–1.02) as compared to the group 1). As in all-cause dementia patients, all dosages of statin medication were negatively associated with VaD (OR 0.61 (95% CI: 0.47–0.77) for low dosage, OR 0.77 (95% CI: 0.68–0.87) for medium dosage and OR 0.74 (95% CI: 0.59–0.92) for high dosage statin) (Table 5B).

DISCUSSION

Main findings

In this retrospective case-control study of more than 24,000 patients aged 65 or older treated in general practices in Germany, we found a negative association between the pre-diagnostic use of all dosages of statin therapy and the development of all-cause dementia and VaD. We found a very slight association between elevated LDL-C and the onset of VaD and all-cause dementia for LDL-C between 100 mg/dl and 130 mg/dl and between 130 and 160 mg/dl for VaD compared with LDL-C less than 100 mg/dl and for LDL-C between 100 and 130 mg/dl for all-cause dementia.

Interpretation of findings

Although the role of increased LDL-C levels in blood and statin use in the development of dementia has been debated intensively in recent decades, it remains ambiguous. Since statins are the most commonly prescribed cholesterol-lowering agents [15], the effect of high LDL-C and the effect of statins should be considered together.

The first result of our analysis was the negative association between the use of statins and the development of either all-cause dementia or VaD. This finding is consistent with several other studies. For example, in 2000, a case-control study in the UK found that statin use had a protective effect with regard to dementia. In 2002, a retrospective study including 655 patients showed that statin use had a protective effect with regard to the development of both all-cause dementia and VAD while adjusting for LDL-C [17]. A few years later in 2008, a prospective study involving almost 7,000 participants in Rotterdam found an association between any use of statins and AD adjusting for total cholesterol [18]. Another study later replicated these results for AD [10].

Our results regarding statin use also revealed that the association between statin use and all-cause dementia or VaD did not differ based on the statin dosage level. Previous studies on this topic have generally examined statin use on the basis of lower classification levels such as “never” or “any” use of statins in this context [10 , 17], but to the best of our knowledge, no study has yet examined the association between dementia and statin use across low-, medium-, or high-dosage statin groups adjusting for LDL-C in German practices. Nevertheless, in 2019 a longitudinal cohort study in Taiwan examined the association between high-exposure statin use and dementia based on the daily dose and found a stronger protective effect in high-exposure statins than in low-exposure doses [30]. Additionally, a meta-analysis from 2018 conducted a dose-response study and found that an increment of 5 mg in the mean daily dose of statins was associated with an 11% decrease in dementia risk [31]. This is in line with our result for all-cause dementia. The protective effect of statins increases as the dosage changes from low to medium. One underlying study of this meta-analysis also examined the role of statins in preventing dementia by categorizing the mean daily dose in mg (<10 mg, between 10 and 20 mg and≥20 mg) [32], but did not apply the same classification into low, medium, and high dosages based on the different types of statins [29] as in our study. They found a significant association between the lowest statin group and the risk of developing all-cause dementia and no significant association between this group and the risk of developing non-AD dementia, which usually takes the form of VaD. Nevertheless, as this study did not adjust for LDL cholesterol levels and only included a cohort of type 2 diabetes patients, these results are hardly comparable with our own. Finally, it could be argued that the differences observed between VaD and all-cause dementia could also be due to a smaller sample size in the subgroup analysis for VaD.

Our findings that there is a very slight negative association between elevated LDL-C levels between 100 and 130 mg/dl for all-cause dementia and between 100 and 160 mg/dl for VaD might be so small that they are clinically not relevant. The rest of our results show no association between elevated LDL-C levels and the onset of both all-cause dementia and VaD and are consistent with those of several previous studies: In 1995, a Japanese prospective study examined over 800 patients without dementia at baseline with a follow-up period of 7 years and found no significant association between LDL-C and both AD and VaD [13] However, the authors did not adjust for the use of statins. Almost 10 years later, the cross-sectional element of an American study of 4,316 Medicare recipients replicated these findings while adjusting for statins [10]. Finally, in 2014, a prospective study including over 7,000 elderly subjects did not find any significant association between elevated LDL-C levels and both all-cause dementia and AD without adjusting for statins [11].

In contrast to these findings, several studies did find a possible relationship between elevated LDL-C levels and dementia. For example, a meta-analysis from 2020 investigating the impact of LDL-C on AD found that elevated concentrations of LDL-C (>121 mg/dl) might increase the risk of AD in patients aged 60–70 years, but the authors explicitly excluded all studies that involved patients with statin use and this review is therefore based on a smaller number of patients (2,266 AD patients and 4,767 controls in total) [8]. Other studies that found an association mainly measured cholesterol levels in mid-life and had a longer follow-up period [7] or took the form of prospective studies (like the prospective element of [10]).

We found slight differences between the different LDL-C categories for all-cause dementia and VaD patients. There was a slightly decreased risk of developing all-cause dementia in patients with a mean LDL-C value of over 100 mg/dl and this risk was slightly higher when the LDL-C level was over 130 mg/dl. For VaD, the risk of developing VaD decreased with increasing LDL-C levels of over 100 mg/dl. Interestingly, the study conducted by Reitz et al. [10] in 2004 also classified patients into different LDL-C groups (first≤96.5 mg/dl, second 96.51–118.8 mg/dl, third 118.81–142.8 mg/dl, and fourth ≥142.76 mg/dl) [10]. They adjusted for sex, age, education, and race (Hispanic, Black, and White), body mass index, diabetes, heart disease, hypertension, and apolipoprotein E genotype [10]. In the cross-sectional analysis, the risk of AD was higher in LDL-C Groups 2 and 4 than in patients with an LDL-C level ≤96.5 mg/dl (Group 1) in Model 1, and only the highest LDL-C group appeared to have a higher risk of developing AD in the second model. This is not totally in line with our results for all-cause dementia, since we found no higher risk in LDL-C Groups 3 and 4 than in the lowest group. The results for VaD are also interesting. The main result, namely that there is no significant association in the cross-sectional part of the study, is in line with our findings. However, the study found an increasing risk of VaD with increasing LDL-C levels in both models, whereas in our study this risk decreased as LDL-C levels increased. These differences might be due to slightly different classifications of the LDL-C groups or the fact that we are regarding all-cause dementia including AD, but not solely AD. In addition, the authors adjusted for variables we did not consider (i.e., education and race, or body mass index, and apolipoprotein E genotype). Education and race were statistically significant risk factors for VaD and AD, and the homozygous and heterozygous variant of the apolipoprotein E genotype was a significant risk factor for AD [10]. Interestingly, a study in 2002 [33] found lower levels of LDL-C in VaD patients than in AD patients, which might explain why, in our analysis, the middle LDL-C level groups are slightly associated with dementia. Differences between all-cause dementia and VaD in our study could possibly be due to differences in the sample size. There is another study [11] that analyzed the impact of LDL-C on dementia and AD using a categorization of the LDL-C values (<119.23 mg/dl or ≥163.85 mg/dl while the group in the middle was the reference group). Although they used a different reference group, they found the highest risk (not significant) in the highest LDL-C quartile [11] which is in line with our result for all-cause dementia.

In total, the results from our study suggest an effect of statins on the dementia pathogenesis independent of LDL-C. A review from 2011 discussed the diverse effects of statins including reducing inflammation processes [34]. The review remarks that these effects are independent of lowering cholesterol [34]. Literature states the contribution of neuroinflammation to the pathogenesis of dementia [5]. Summarizing these findings, statins might be functioning as anti-inflammatory agents in the pathogenesis of dementia and therefore might lower the risk to develop the cognitive disease.

Strengths and limitations

The strengths of this study include the large sample size of more than 24,000 patients and the fact that real-world data were used. The strength of using real-world data in this setting is that normal prescription behavior and diagnostics is ensured. In addition, the representativeness of the database is ensured [25].

There are also some limitations to this study that must be considered. First, although the interindividual variation in the LDL-C response to a given dose of a given statin can be very large, this individual LDL-C goal has not been considered in the study. Second, the severity of the dementia is unfortunately not documented in the database, although the association between statin usage and cholesterol may differ for different dementia severities (i.e., mild/moderate/severe dementia). Third, this study only considered medical and demographic factors that could impact the development of dementia. No information about environmental factors such as socio-economic status, education, lifestyle, physical activity, smoking status, etc., was available for analysis. Additionally, genetic factors (for example differences in the APOE4 allele) were not considered although they might affect outcomes [35]. Fourth, there might be a certain percentage of misclassified diagnoses between VaD and AD (which is included here in all-cause dementia) due to similar symptomatology [8]. Furthermore, due to the low imaging rate (CT/MRI) in routine care, the validity of the diagnosis of VaD may be limited [36]. Fifth, the case-control study design impairs the examination of causality and temporality behind the founded associations.

Conclusion

A negative association was found between the use of all dosages of statin therapy and all-cause dementia and VaD in elderly patients in general practices in Germany. These results support the theory that the use of statin medication plays an important role in preventing cognitive impairment. Further studies are needed to gain a better insight into the temporary aspect and causality behind these associations.

DISCLOSURE STATEMENT

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/20-1176r2).

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